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Ring chromosome 1 syndrome is an autosomal anomaly characterized by variable clinical features, most commonly including significant intrauterine and postnatal growth failure, developmental delay, intellectual disability, microcephaly, and dysmorphic facial features. Some less frequent clinical features are dysgenesis of corpus callosum, atrial septal defect, rocker bottom feet and clinodactyly.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Ring chromosome 1 syndrome
|
c0265395
| 7,300 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1437
| 2021-01-23T18:00:12 |
{"gard": ["1320"], "mesh": ["C535361"], "umls": ["C0265395", "C1519099"], "icd-10": ["Q93.2"], "synonyms": ["Ring 1", "Ring chromosome 1", "r(1) syndrome"]}
|
Trichophagia
SpecialtyPsychiatry
Trichophagia is the compulsive eating of hair associated with trichotillomania (hair pulling).[1] In trichophagia, people with trichotillomania also ingest the hair that they pull; in extreme cases this can lead to a hair ball (trichobezoar).[2] The term is derived from ancient Greek θρίξ, thrix ("hair") and φαγεῖν, phagein ("to eat").
## Contents
* 1 Signs and symptoms
* 2 Prognosis
* 3 History
* 4 In media
* 5 References
* 6 External links
## Signs and symptoms[edit]
Trichophagia is characterized by the person eating hair, usually their own; primarily after pulling it out. Most often, hair is pulled out and then the ends of the root bulb are eaten, or occasionally the hair shaft itself. The hair eventually collects in the gastrointestinal tract (on occasion, and depending upon severity of symptoms) causing indigestion and stomach pain.[citation needed] Ritual is a strong factor, and may involve touching the root bulb to the lips, tasting the hair, and occasionally chewing it. Sometimes those with the disorder may even eat the hair of others. In the psychiatric field it is considered a compulsive psychological disorder.[citation needed]
## Prognosis[edit]
Rapunzel syndrome, an extreme form of trichobezoar in which the "tail" of the hair ball extends into the intestines, and can be fatal if misdiagnosed.[2][3][4][5] In some cases, surgery may be required to remove the mass;[6] a trichobezoar weighing 4.5 kilograms (9.9 lb) was removed from the stomach of an 18-year-old woman with trichophagia.[7]
## History[edit]
Trichophagia is most often covered in the medical literature only "as a rare symptom of trichotillomania."[8] In the 18th century French doctor M. Baudamant described the condition in a 16-year-old boy.[8]
## In media[edit]
Trichophagia is mentioned in the 1000 Ways to Die episode "Stupid Is As Stupid Dies" featuring a young woman who died from it. It is also mentioned in Grey's Anatomy season 9 episode 11 "The End Is the Beginning Is the End". As well as Season 3 episode 16 of “The Resident,” “Reverse Cinderella.”
## References[edit]
1. ^ Chamberlain SR, Menzies L, Sahakian BJ, Fineberg NA (April 2007). "Lifting the veil on trichotillomania". Am J Psychiatry. 164 (4): 568–74. doi:10.1176/appi.ajp.164.4.568. PMID 17403968.
2. ^ a b Sah DE, Koo J, Price VH (2008). "Trichotillomania" (PDF). Dermatol Ther. 21 (1): 13–21. doi:10.1111/j.1529-8019.2008.00165.x. PMID 18318881.[dead link]
3. ^ Ventura DE, Herbella FA, Schettini ST, Delmonte C (2005). "Rapunzel syndrome with a fatal outcome in a neglected child". J. Pediatr. Surg. 40 (10): 1665–7. doi:10.1016/j.jpedsurg.2005.06.038. PMID 16227005.
4. ^ Pul N, Pul M (1996). "The Rapunzel syndrome (trichobezoar) causing gastric perforation in a child: a case report". Eur. J. Pediatr. 155 (1): 18–9. doi:10.1007/bf02115620. PMID 8750804.
5. ^ Matejů E, Duchanová S, Kovac P, Moravanský N, Spitz DJ (September 2009). "Fatal case of Rapunzel syndrome in neglected child". Forensic Sci. Int. 190 (1–3): e5–7. doi:10.1016/j.forsciint.2009.05.008. PMID 19505779.
6. ^ Gorter RR, Kneepkens CM, Mattens EC, Aronson DC, Heij HA (May 2010). "Management of trichobezoar: case report and literature review". Pediatr. Surg. Int. 26 (5): 457–63. doi:10.1007/s00383-010-2570-0. PMC 2856853. PMID 20213124.
7. ^ Levy RM, Komanduri S (November 2007). "Images in clinical medicine. Trichobezoar". N. Engl. J. Med. 357 (21): e23. doi:10.1056/NEJMicm067796. PMID 18032760. Lay summary – CNN (2007-11-22).
8. ^ a b Grant JE, Odlaug BL (2008). "Clinical characteristics of trichotillomania with trichophagia". Compr Psychiatry. 49 (6): 579–84. doi:10.1016/j.comppsych.2008.05.002. PMC 2605948. PMID 18970906. Citing Baudamant M. "Description de deux masses de cheveux trouvee dans l'estomac et les intestines d'un jeune garcon age de seize ans." Hist Soc Roy Med, Paris. 1777–1779;2:262–63.
## External links[edit]
Classification
D
* ICD-10: F98.4 (ILDS F98.420)
* The TLC Foundation for Body-Focused Repetitive Behaviors
* v
* t
* e
Human hair
Classification
by type
* Lanugo
* Androgenic
* Terminal
* Vellus
by location
* Body
* Ear
* Nose
* Eyebrow
* unibrow
* Eyelash
* Underarm
* Chest
* Abdominal
* Pubic
* Leg
Head hairstyles
(list)
* Afro
* Afro puffs
* Asymmetric cut
* Bald
* Bangs
* Beehive
* Big hair
* Blowout
* Bob cut
* Bouffant
* Bowl cut
* Braid
* Brush cut
* Bun (odango)
* Bunches
* Burr
* Businessman cut
* Butch cut
* Buzz cut
* Caesar cut
* Chignon
* Chonmage
* Chupryna
* Comb over
* Conk
* Cornrows
* Crew cut
* Crochet braids
* Croydon facelift
* Curly hair
* Curtained hair
* Devilock
* Dido flip
* Digital perm
* Dreadlocks
* Duck's ass
* Eton crop
* Extensions
* Feathered hair
* Finger wave
* Flattop
* Fontange
* French braid
* French twist
* Fringe
* Frosted tips
* Hair crimping
* Harvard clip
* High and tight
* Hime cut
* Historical Christian hairstyles
* Hi-top fade
* Induction cut
* Ivy League
* Jewfro
* Jheri curl
* Kiss curl
* Layered hair
* Liberty spikes
* Long hair
* Lob cut
* Marcelling
* Mod cut
* Mohawk
* Mullet
* 1950s
* 1980s
* Pageboy
* Part
* Payot
* Pigtail
* Pixie cut
* Polish halfshaven head
* Pompadour
* Ponytail
* Punch perm
* Princeton
* Professional cut
* Queue
* Quiff
* Rattail
* Razor cut
* Regular haircut
* Ringlets
* Shag
* Shape-Up
* Shimada
* Short back and sides
* Short brush cut
* Short hair
* Spiky hair
* Straight hair
* Standard haircut
* Surfer hair
* Taper cut
* Temple Fade
* Tonsure
* Updo
* Undercut
* Waves
* Widow's peak
* Wings
Facial hair
(list)
* Beard
* Chinstrap
* Goatee
* Shenandoah
* Soul patch
* Van Dyke
* Moustache
* Fu Manchu
* handlebar
* horseshoe
* pencil
* toothbrush
* walrus
* Designer stubble
* Sideburns
Hair loss
cosmetic
* Removal
* waxing
* threading
* plucking
* chemical
* electric
* laser
* IPL
* Shaving
* head
* leg
* cream
* brush
* soap
* Razor
* electric
* safety
* straight
other
* Alopecia
* areata
* totalis
* universalis
* Frictional alopecia
* Male-pattern hair loss
* Hypertrichosis
* Management
* Trichophilia
* Trichotillomania
* Pogonophobia
Haircare products
* Brush
* Clay
* Clipper
* Comb
* Conditioner
* Dryer
* Gel
* Hot comb
* Iron
* Mousse
* Pomade
* Relaxer
* Rollers
* Shampoo
* Spray
* Wax
Haircare techniques
* Backcombing
* Crimping
* Curly Girl Method
* Hair cutting
* Perm
* Shampoo and set
* Straightening
Related topics
* Afro-textured hair (kinky hair)
* Beard and haircut laws by country
* Bearded lady
* Barber (pole)
* Eponymous hairstyle
* Frizz
* Good hair
* Hairdresser
* Hair fetishism (pubic)
* Hair follicle
* Hair growth
* Hypertrichosis
* Trichotillomania
* v
* t
* e
Emotional and behavioral disorders
Emotional/behavioral
* ADHD
* Conduct disorder
* Oppositional defiant disorder
* Emotional/behavioral disorder (EBD)
* Separation anxiety
* Social functioning
* Selective mutism
* RAD
* DAD
* Tic disorders
* Tourette syndrome
* Speech disorders
* Stuttering
* Cluttering
* Stereotypic movement disorder
* Elimination disorders
* Enuresis
* Encopresis
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Trichophagia
|
c0584961
| 7,301 |
wikipedia
|
https://en.wikipedia.org/wiki/Trichophagia
| 2021-01-18T18:41:36 |
{"icd-10": ["F98.4"], "wikidata": ["Q1578799"]}
|
Hepatoerythropioetic porphyria (HEP) is a very rare form of chronic hepatic porphyria (see this term) characterized by bullous photodermatitis.
## Epidemiology
Fewer than 40 cases of HEP have been described.
## Clinical description
The disease starts in childhood. The principle clinical signs include fragile skin, bullous cutaneous lesions that are sometimes erosive, and even mutilating on the surface of the skin exposed to the sun (hands, face). Hepatoerythropioetic porphria corresponds to homozygous and composite heterozygous cases of porphyria cutanea tarda (see this term).
## Etiology
It is caused by a deficiency of uroporphyrinogen decarboxylase (URO-D; the fifth enzyme in the heme biosynthesis pathway) that leads to an accumulation of uroporphrin in the liver. The enzyme deficiency is a result of a mutation of the URO-D gene. At least 30 different mutations have been described, of which one substitution mutation dominates (G281D).
## Diagnostic methods
Diagnosis is based on evidence of an accumulation of porphyrins in urine, on their chromatographic profile, and on an elevated concentration of porphyrins in the blood. Evidence of a major deficit (<10%) of URO-D in red blood cells allows a confirmed diagnosis.
## Differential diagnosis
Differential diagnosis is mainly Günther disease (see this term).
## Genetic counseling
Transmission is autosomal recessive. Genetic counseling should be offered to affected families to identify individuals susceptible to developing or transmitting the disease.
## Management and treatment
Management includes protecting the skin from light and, in cases of anemia, blood transfusions. Treatment with hydroxyurea and splenectomy is rarely necessary.
## Prognosis
The long term prognosis is favorable.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Hepatoerythropoietic porphyria
|
c0162569
| 7,302 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=95159
| 2021-01-23T18:14:31 |
{"gard": ["6169"], "mesh": ["D017121"], "omim": ["176100"], "umls": ["C0162569", "C0268324"], "icd-10": ["E80.2"], "synonyms": ["HEP"]}
|
For a discussion of genetic heterogeneity of hematocrit/hemoglobin quantitative trait loci, see HCHGQ1 (609319).
Mapping
Chambers et al. (2009) carried out a genomewide association study of hemoglobin levels in 16,001 individuals of European and Indian Asian ancestry. The most closely associated SNP, rs855791, results in a nonsynonymous valine736-to-alanine (V736A) change in the serine protease domain of the TMPRSS6 gene (609862) on chromosome 22q12-q13 and a blood hemoglobin concentration of 0.13 (95% CI, 0.09-0.17) g/dl lower per copy of the allele A (p = 1.6 x 10(-13)).
In a genomewide association study in 2,516 adolescent and 2,302 adult individuals from 2,277 Australian twin families, Benyamin et al. (2009) identified an association of SNPs in TMPRSS6 to serum iron (rs855791, combined P = 1.5 x 10(-20)), transferrin saturation (combined P = 2.2 x 10(-23)), and erythrocyte mean cell volume (MCV, combined P = 1.1 x 10(-10)). They also found suggestive evidence of association with blood hemoglobin levels (combined p = 5.3 x 10(-7)). Benyamin et al. (2009) concluded that their findings demonstrated the involvement of TMPRSS6 in control of iron homeostasis and in normal erythropoiesis. The authors referred to the amino acid substitution represented by rs855791 as A736V.
Van der Harst et al. (2012) carried out a genomewide association study of hemoglobin concentration and related parameters in up to 135,367 individuals, and identified 75 independent genetic loci associated with one or more red blood cell phenotypes at p less than 10(-8), which together explain 4 to 9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, van der Harst et al. (2012) identified 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have hematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses, van der Harst et al. (2012) identified potential causal genetic variants at 41 loci. The parameters measured included hemoglobin, mean cell hemoglobin, mean cell hemoglobin concentration, mean cell volume, packed cell volume, and red blood cell count. Van der Harst et al. (2012) found association of the SNP (rs855791) with mean cell hemoglobin (p = 1.0 x 10(-69)). They also found association of a SNP at 22q13, rs140522, with mean cell volume (p = 4.5 x 10(-23)).
In a population-based study of 1,832 Dutch individuals with a mean age of 62 years who were genotyped for SNPs within the TMPRSS6 gene, Galesloot et al. (2013) found that a G-to-A SNP (rs855791) had the most significant association with iron and transferrin saturation (p = 3.4 x 10(-12) and 8.5 x 10(-14), respectively). This association was independent of serum hepcidin (HAMP; 606464). However, the SNP was significantly associated with the ratio of hepcidin to ferritin and hepcidin to transferrin saturation. The findings did not support the hypothesis that variation in the TMPRSS6 gene influences iron parameters by affecting hepcidin expression in response to systemic iron concentration.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
HEMATOCRIT/HEMOGLOBIN QUANTITATIVE TRAIT LOCUS 3
|
c2750092
| 7,303 |
omim
|
https://www.omim.org/entry/613284
| 2019-09-22T15:59:05 |
{"omim": ["613284"], "synonyms": ["Alternative titles", "HEMATOCRIT/HEMOGLOBIN QUANTITATIVE TRAIT LOCUS ON CHROMOSOME 22"]}
|
Heart rate that exceeds the normal resting rate
Tachycardia
Other namesTachyarrhythmia
ECG showing sinus tachycardia with a rate of about 100 beats per minute
Pronunciation
* Tachycardia /tækiˈkɑːrdiə/, tachyarrhythmia /tækiəˈrɪðmiə/
SpecialtyCardiology
Differential diagnosisPalpitations, Ventricular tachycardia, Supraventricular tachycardia, Paroxysmal tachycardia, Junctional ectopic tachycardia, Sinus tachycardia, Atrial tachycardia, AV nodal reentrant tachycardia
Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate.[1] In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults.[1] Heart rates above the resting rate may be normal (such as with exercise) or abnormal (such as with electrical problems within the heart).
## Contents
* 1 Complications
* 2 Causes
* 3 Diagnosis
* 3.1 Differential diagnosis
* 3.1.1 Sinus
* 3.1.2 Ventricular
* 3.1.3 Supraventricular
* 3.1.3.1 Atrial fibrillation
* 3.1.3.2 AV nodal reentrant tachycardia
* 3.1.3.3 AV reentrant tachycardia
* 3.1.3.4 Junctional tachycardia
* 4 Management
* 4.1 Unstable
* 5 Terminology
* 6 See also
* 7 References
* 8 External links
Sound of a student's heart during tachycardia.
Auscultation of a 14 year old female's heart during an episode of tachyarrhythmia.
* * *
Problems playing this file? See media help.
## Complications[edit]
Tachycardia can lead to fainting.[2]
When the rate of blood flow becomes too rapid, or fast blood flow passes on damaged endothelium, it increases the friction within vessels resulting in turbulence and other disturbances.[3] According to the Virchow's triad, this is one of the three conditions that can lead to thrombosis (i.e., blood clots within vessels).
## Causes[edit]
Some causes of tachycardia include:
* Adrenergic storm
* Anaemia
* Anxiety
* Atrial fibrillation
* Atrial flutter
* Atrial tachycardia
* AV nodal reentrant tachycardia
* Brugada syndrome
* Early manifestation of circulatory shock
* Dysautonomia
* Exercise
* Fear
* Hypoglycemia
* Hypovolemia
* Hyperthyroidism
* Hyperventilation
* Junctional tachycardia
* Multifocal atrial tachycardia
* Pacemaker mediated
* Pain
* Pheochromocytoma
* Sinus tachycardia
* Sleep deprivation[4]
* Supraventricular tachycardia
* Ventricular tachycardia
* Wolff–Parkinson–White syndrome
Drug related:
* Alcohol
* Stimulants
* Cannabis (drug)
* Drug withdrawal
* Tricyclic antidepressants
* Nefopam
* Opioids (rare)
## Diagnosis[edit]
The upper threshold of a normal human resting heart rate is based on age. Cutoff values for tachycardia in different age groups are fairly well standardized; typical cutoffs are listed below:[5]
* 1–2 days: Tachycardia >159 beats per minute (bpm)
* 3–6 days: Tachycardia >166 bpm
* 1–3 weeks: Tachycardia >182 bpm
* 1–2 months: Tachycardia >179 bpm
* 3–5 months: Tachycardia >186 bpm
* 6–11 months: Tachycardia >169 bpm
* 1–2 years: Tachycardia >151 bpm
* 3–4 years: Tachycardia >137 bpm
* 5–7 years: Tachycardia >133 bpm
* 8–11 years: Tachycardia >130 bpm
* 12–15 years: Tachycardia >119 bpm
* >15 years – adult: Tachycardia >100 bpm
Heart rate is considered in the context of the prevailing clinical picture. For example, in sepsis >90 bpm is considered tachycardia.
When the heart beats excessively or rapidly, the heart pumps less efficiently and provides less blood flow to the rest of the body, including the heart itself. The increased heart rate also leads to increased work and oxygen demand by the heart, which can lead to rate related ischemia.[6]
Relative tachycardia involves a greater increase in rate than would be expected in a given illness state.[citation needed]
### Differential diagnosis[edit]
12 lead electrocardiogram showing a ventricular tachycardia (VT)
An electrocardiogram (ECG) is used to classify the type of tachycardia. They may be classified into narrow and wide complex based on the QRS complex.[7] Equal or less than 0.1s for narrow complex.[8] Presented order of most to least common, they are:[7]
* Narrow complex
* Sinus tachycardia, which originates from the sino-atrial (SA) node, near the base of the superior vena cava
* Atrial fibrillation
* Atrial flutter
* AV nodal reentrant tachycardia
* Accessory pathway mediated tachycardia
* Atrial tachycardia
* Multifocal atrial tachycardia
* Cardiac Tamponade
* Junctional tachycardia (rare in adults)
* Wide complex
* Ventricular tachycardia, any tachycardia that originates in the ventricles
* Any narrow complex tachycardia combined with a problem with the conduction system of the heart, often termed "supraventricular tachycardia with aberrancy"
* A narrow complex tachycardia with an accessory conduction pathway, often termed "supraventricular tachycardia with pre-excitation" (e.g. Wolff–Parkinson–White syndrome)
* Pacemaker-tracked or pacemaker-mediated tachycardia
Tachycardias may be classified as either narrow complex tachycardias (supraventricular tachycardias) or wide complex tachycardias. Narrow and wide refer to the width of the QRS complex on the ECG. Narrow complex tachycardias tend to originate in the atria, while wide complex tachycardias tend to originate in the ventricles. Tachycardias can be further classified as either regular or irregular.
#### Sinus[edit]
Main article: Sinus tachycardia
The body has several feedback mechanisms to maintain adequate blood flow and blood pressure. If blood pressure decreases, the heart beats faster in an attempt to raise it. This is called reflex tachycardia. This can happen in response to a decrease in blood volume (through dehydration or bleeding), or an unexpected change in blood flow. The most common cause of the latter is orthostatic hypotension (also called postural hypotension). Fever, hyperventilation, diarrhea and severe infections can also cause tachycardia, primarily due to increase in metabolic demands.
An increase in sympathetic nervous system stimulation causes the heart rate to increase, both by the direct action of sympathetic nerve fibers on the heart and by causing the endocrine system to release hormones such as epinephrine (adrenaline), which have a similar effect. Increased sympathetic stimulation is usually due to physical or psychological stress. This is the basis for the so-called fight-or-flight response, but such stimulation can also be induced by stimulants such as ephedrine, amphetamines or cocaine. Certain endocrine disorders such as pheochromocytoma can also cause epinephrine release and can result in tachycardia independent of nervous system stimulation. Hyperthyroidism can also cause tachycardia.[9] The upper limit of normal rate for sinus tachycardia is thought to be 220 bpm minus age.
#### Ventricular[edit]
Main article: Ventricular tachycardia
Ventricular tachycardia (VT or V-tach) is a potentially life-threatening cardiac arrhythmia that originates in the ventricles. It is usually a regular, wide complex tachycardia with a rate between 120 and 250 beats per minute. A medically significant subvariant of Ventricular Tachycardia is called Torsades de Pointes (literally meaning "Twisting of the Points" due to its appearance on an EKG), which tends to result from a long QT interval.[10]
Both of these rhythms normally last for only a few seconds to minutes (paroxysmal tachycardia), but if VT persists it is extremely dangerous, often leading to ventricular fibrillation.[citation needed]
#### Supraventricular[edit]
Main article: Supraventricular tachycardia
This is a type of tachycardia that originates from above the ventricles, such as the atria. It is sometimes known as paroxysmal atrial tachycardia (PAT). Several types of supraventricular tachycardia are known to exist.[citation needed]
##### Atrial fibrillation[edit]
Atrial fibrillation is one of the most common cardiac arrhythmias. In general, it is an irregular, narrow complex rhythm. However, it may show wide QRS complexes on the ECG if a bundle branch block is present. At high rates, the QRS complex may also become wide due to the Ashman phenomenon. It may be difficult to determine the rhythm's regularity when the rate exceeds 150 beats per minute. Depending on the patient's health and other variables such as medications taken for rate control, atrial fibrillation may cause heart rates that span from 50 to 250 beats per minute (or even higher if an accessory pathway is present). However, new onset atrial fibrillation tends to present with rates between 100 and 150 beats per minute.[citation needed]
##### AV nodal reentrant tachycardia[edit]
AV nodal reentrant tachycardia (AVNRT) is the most common reentrant tachycardia. It is a regular narrow complex tachycardia that usually responds well to the Valsalva maneuver or the drug adenosine. However, unstable patients sometimes require synchronized cardioversion. Definitive care may include catheter ablation.[citation needed]
##### AV reentrant tachycardia[edit]
AV reentrant tachycardia (AVRT) requires an accessory pathway for its maintenance. AVRT may involve orthodromic conduction (where the impulse travels down the AV node to the ventricles and back up to the atria through the accessory pathway) or antidromic conduction (which the impulse travels down the accessory pathway and back up to the atria through the AV node). Orthodromic conduction usually results in a narrow complex tachycardia, and antidromic conduction usually results in a wide complex tachycardia that often mimics ventricular tachycardia. Most antiarrhythmics are contraindicated in the emergency treatment of AVRT, because they may paradoxically increase conduction across the accessory pathway.[citation needed]
##### Junctional tachycardia[edit]
Junctional tachycardia is an automatic tachycardia originating in the AV junction. It tends to be a regular, narrow complex tachycardia and may be a sign of digitalis toxicity.[citation needed]
## Management[edit]
The management of tachycardia depends on its type (wide complex versus narrow complex), whether or not the person is stable or unstable, and whether the instability is due to the tachycardia.[7] Unstable means that either important organ functions are affected or cardiac arrest is about to occur.[7]
### Unstable[edit]
In those that are unstable with a narrow complex tachycardia, intravenous adenosine may be attempted.[7] In all others immediate cardioversion is recommended.[7]
## Terminology[edit]
The word tachycardia came to English from New Latin as a neoclassical compound built from the combining forms tachy- \+ -cardia, which are from the Greek ταχύς tachys, "quick, rapid" and καρδία, kardia, "heart". As a matter both of usage choices in the medical literature and of idiom in natural language, the words tachycardia and tachyarrhythmia are usually used interchangeably, or loosely enough that precise differentiation is not explicit. Some careful writers have tried to maintain a logical differentiation between them, which is reflected in major medical dictionaries[11][12][13] and major general dictionaries.[14][15][16] The distinction is that tachycardia be reserved for the rapid heart rate itself, regardless of cause, physiologic or pathologic (that is, from healthy response to exercise or from cardiac arrhythmia), and that tachyarrhythmia be reserved for the pathologic form (that is, an arrhythmia of the rapid rate type). This is why five of the previously referenced dictionaries do not enter cross-references indicating synonymy between their entries for the two words (as they do elsewhere whenever synonymy is meant), and it is why one of them explicitly specifies that the two words not be confused.[13] But the prescription will probably never be successfully imposed on general usage, not only because much of the existing medical literature ignores it even when the words stand alone but also because the terms for specific types of arrhythmia (standard collocations of adjectives and noun) are deeply established idiomatically with the tachycardia version as the more commonly used version. Thus SVT is called supraventricular tachycardia more than twice as often as it is called supraventricular tachyarrhythmia; moreover, those two terms are always completely synonymous—in natural language there is no such term as "healthy/physiologic supraventricular tachycardia". The same themes are also true of AVRT and AVNRT. Thus this pair is an example of when a particular prescription (which may have been tenable 50 or 100 years earlier) can no longer be invariably enforced without violating idiom. But the power to differentiate in an idiomatic way is not lost, regardless, because when the specification of physiologic tachycardia is needed, that phrase aptly conveys it.
## See also[edit]
* Postural orthostatic tachycardia syndrome
## References[edit]
1. ^ a b Awtry, Eric H.; Jeon, Cathy; Ware, Molly G. (2006). Blueprints cardiology (2nd ed.). Malden, Mass.: Blackwell. p. 93. ISBN 9781405104647.
2. ^ "Passing Out (Syncope) Caused by Arrhythmias".
3. ^ Kushner, Abigail; West, William P.; Pillarisetty, Leela Sharath (2020), "Virchow Triad", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 30969519, retrieved 2020-06-18
4. ^ Rangaraj VR, Knutson KL (February 2016). "Association between sleep deficiency and cardiometabolic disease: implications for health disparities". Sleep Med. 18: 19–35. doi:10.1016/j.sleep.2015.02.535. PMC 4758899. PMID 26431758.
5. ^ Custer JW, Rau RE, eds. Johns Hopkins: The Harriet Lane Handbook. 18th ed. Philadelphia, PA: Mosby Elsevier Inc; 2008. Data also available through eMedicine: Pediatrics, Tachycardia.
6. ^ Harrison's Principles of Internal Medicine, 17th Edition
7. ^ a b c d e f Neumar RW, Otto CW, Link MS, et al. (November 2010). "Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care". Circulation. 122 (18 Suppl 3): S729–67. doi:10.1161/CIRCULATIONAHA.110.970988. PMID 20956224.
8. ^ Pieper, Stephen J.; Stanton, Marshall S. (April 1995). "Narrow QRS Complex Tachycardias". Mayo Clinic Proceedings. 70 (4): 371–375. doi:10.4065/70.4.371. PMID 7898144.
9. ^ Barker RL, Burton JR, Zieve, PD eds. Principles of Ambulatory Medicine. Sixth Edition. Philadelphia, PA: Lippinocott, Wilkins & Williams 2003
10. ^ MERCK Manual Profesional Edition RET. April 19, 2019 18:37 CST. https://www.merckmanuals.com/professional/cardiovascular-disorders/arrhythmias-and-conduction-disorders/long-qt-syndrome-and-torsades-de-pointes-ventricular-tachycardia
11. ^ Elsevier, Dorland's Illustrated Medical Dictionary, Elsevier.
12. ^ Merriam-Webster, Merriam-Webster's Medical Dictionary, Merriam-Webster.
13. ^ a b Wolters Kluwer, Stedman's Medical Dictionary, Wolters Kluwer.
14. ^ Houghton Mifflin Harcourt, The American Heritage Dictionary of the English Language, Houghton Mifflin Harcourt.
15. ^ Merriam-Webster, Merriam-Webster's Collegiate Dictionary, Merriam-Webster.
16. ^ Merriam-Webster, Merriam-Webster's Unabridged Dictionary, Merriam-Webster.
## External links[edit]
Classification
D
* ICD-10: I47-I49, R00.0
* ICD-9-CM: 427, 785.0
* MeSH: D013610
* v
* t
* e
Symptoms and signs relating to the circulatory system
Chest pain
* Referred pain
* Angina
* Levine's sign
Auscultation
* Heart sounds
* Split S2
* S3
* S4
* Gallop rhythm
* Heart murmur
* Systolic
* Functional murmur
* Still's murmur
* Diastolic
* Pulmonary insufficiency
* Graham Steell murmur
* Continuous
* Carey Coombs murmur
* Mitral insufficiency
* Presystolic murmur
* Pericardial friction rub
* Heart click
* Bruit
* carotid
Pulse
* Tachycardia
* Bradycardia
* Pulsus paradoxus
* doubled
* Pulsus bisferiens
* Pulsus bigeminus
* Pulsus alternans
Other
* Palpitations
* Apex beat
* Cœur en sabot
* Jugular venous pressure
* Cannon A waves
* Hyperaemia
*
Shock
* Cardiogenic
* Obstructive
* Hypovolemic
* Distributive
* See further Template:Shock
Cardiovascular disease
Aortic insufficiency
* Collapsing pulse
* De Musset's sign
* Duroziez's sign
* Müller's sign
* Austin Flint murmur
* Mayne's sign
Other endocardium
* endocarditis: Roth's spot
* Janeway lesion/Osler's node
* Bracht–Wachter bodies
Pericardium
* Cardiac tamponade/Pericardial effusion: Beck's triad
* Ewart's sign
Other
* rheumatic fever:
* Anitschkow cell
* Aschoff body
* EKG
* J wave
* Gallavardin phenomenon
Vascular disease
Arterial
* aortic aneurysm
* Cardarelli's sign
* Oliver's sign
* pulmonary embolism
* Right heart strain
* radial artery sufficiency
* Allen's test
* pseudohypertension
* thrombus
* Lines of Zahn
* Adson's sign
* arteriovenous fistula
* Nicoladoni sign
Venous
* Friedreich's sign
* Caput medusae
* Kussmaul's sign
* Trendelenburg test
* superior vena cava syndrome
* Pemberton's sign
* v
* t
* e
Cardiovascular disease (heart)
Ischaemic
Coronary disease
* Coronary artery disease (CAD)
* Coronary artery aneurysm
* Spontaneous coronary artery dissection (SCAD)
* Coronary thrombosis
* Coronary vasospasm
* Myocardial bridge
Active ischemia
* Angina pectoris
* Prinzmetal's angina
* Stable angina
* Acute coronary syndrome
* Myocardial infarction
* Unstable angina
Sequelae
* hours
* Hibernating myocardium
* Myocardial stunning
* days
* Myocardial rupture
* weeks
* Aneurysm of heart / Ventricular aneurysm
* Dressler syndrome
Layers
Pericardium
* Pericarditis
* Acute
* Chronic / Constrictive
* Pericardial effusion
* Cardiac tamponade
* Hemopericardium
Myocardium
* Myocarditis
* Chagas disease
* Cardiomyopathy
* Dilated
* Alcoholic
* Hypertrophic
* Tachycardia-induced
* Restrictive
* Loeffler endocarditis
* Cardiac amyloidosis
* Endocardial fibroelastosis
* Arrhythmogenic right ventricular dysplasia
Endocardium /
valves
Endocarditis
* infective endocarditis
* Subacute bacterial endocarditis
* non-infective endocarditis
* Libman–Sacks endocarditis
* Nonbacterial thrombotic endocarditis
Valves
* mitral
* regurgitation
* prolapse
* stenosis
* aortic
* stenosis
* insufficiency
* tricuspid
* stenosis
* insufficiency
* pulmonary
* stenosis
* insufficiency
Conduction /
arrhythmia
Bradycardia
* Sinus bradycardia
* Sick sinus syndrome
* Heart block: Sinoatrial
* AV
* 1°
* 2°
* 3°
* Intraventricular
* Bundle branch block
* Right
* Left
* Left anterior fascicle
* Left posterior fascicle
* Bifascicular
* Trifascicular
* Adams–Stokes syndrome
Tachycardia
(paroxysmal and sinus)
Supraventricular
* Atrial
* Multifocal
* Junctional
* AV nodal reentrant
* Junctional ectopic
Ventricular
* Accelerated idioventricular rhythm
* Catecholaminergic polymorphic
* Torsades de pointes
Premature contraction
* Atrial
* Junctional
* Ventricular
Pre-excitation syndrome
* Lown–Ganong–Levine
* Wolff–Parkinson–White
Flutter / fibrillation
* Atrial flutter
* Ventricular flutter
* Atrial fibrillation
* Familial
* Ventricular fibrillation
Pacemaker
* Ectopic pacemaker / Ectopic beat
* Multifocal atrial tachycardia
* Pacemaker syndrome
* Parasystole
* Wandering atrial pacemaker
Long QT syndrome
* Andersen–Tawil
* Jervell and Lange-Nielsen
* Romano–Ward
Cardiac arrest
* Sudden cardiac death
* Asystole
* Pulseless electrical activity
* Sinoatrial arrest
Other / ungrouped
* hexaxial reference system
* Right axis deviation
* Left axis deviation
* QT
* Short QT syndrome
* T
* T wave alternans
* ST
* Osborn wave
* ST elevation
* ST depression
* Strain pattern
Cardiomegaly
* Ventricular hypertrophy
* Left
* Right / Cor pulmonale
* Atrial enlargement
* Left
* Right
* Athletic heart syndrome
Other
* Cardiac fibrosis
* Heart failure
* Diastolic heart failure
* Cardiac asthma
* Rheumatic fever
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
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Tachycardia
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c0039231
| 7,304 |
wikipedia
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https://en.wikipedia.org/wiki/Tachycardia
| 2021-01-18T18:35:56 |
{"mesh": ["D013610"], "umls": ["C0039231", "C4020868"], "wikidata": ["Q209583"]}
|
Photoleukomelanodermatitis of Kobori
SpecialtyDermatology
Photoleukomelanodermatitis of Kobori is a cutaneous condition, a dyschromic drug eruption that occurs after ingestion of afloqualone, thiazides or tetracyclines, followed by exposure to sunlight.[1]
## See also[edit]
* Leukotriene receptor antagonist-associated Churg–Strauss syndrome
* List of cutaneous conditions
## References[edit]
1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 1-4160-2999-0.
This dermatology article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Photoleukomelanodermatitis of Kobori
|
None
| 7,305 |
wikipedia
|
https://en.wikipedia.org/wiki/Photoleukomelanodermatitis_of_Kobori
| 2021-01-18T19:06:24 |
{"wikidata": ["Q7187821"]}
|
Sézary syndrome is an aggressive form of a type of blood cancer called cutaneous T-cell lymphoma. Cutaneous T-cell lymphomas occur when certain white blood cells, called T cells, become cancerous; these cancers characteristically affect the skin, causing different types of skin lesions. In Sézary syndrome, the cancerous T cells, called Sézary cells, are present in the blood, skin, and lymph nodes. A characteristic of Sézary cells is an abnormally shaped nucleus, described as cerebriform.
People with Sézary syndrome develop a red, severely itchy rash (erythroderma) that covers large portions of their body. Sézary cells are found in the rash. However, the skin cells themselves are not cancerous; the skin problems result when Sézary cells move from the blood into the skin. People with Sézary syndrome also have enlarged lymph nodes (lymphadenopathy). Other common signs and symptoms of this condition include hair loss (alopecia), skin swelling (edema), thickened skin on the palms of the hands and soles of the feet (palmoplantar keratoderma), abnormalities of the fingernails and toenails, and lower eyelids that turn outward (ectropion). Some people with Sézary syndrome are less able to control their body temperature than people without the condition.
The cancerous T cells can spread to other organs in the body, including the lymph nodes, liver, spleen, and bone marrow. In addition, affected individuals have an increased risk of developing another lymphoma or other type of cancer.
Sézary syndrome most often occurs in adults over age 60 and usually progresses rapidly; historically, affected individuals survived an average of 2 to 4 years after development of the condition, although survival has improved with newer treatments.
Although Sézary syndrome is sometimes referred to as a variant of another cutaneous T-cell lymphoma called mycosis fungoides, these two cancers are generally considered separate conditions.
## Frequency
Sézary syndrome is a rare condition, although its prevalence is unknown. It is the second most common form of cutaneous T-cell lymphoma after mycosis fungoides, accounting for approximately 3 to 5 percent of cases of cutaneous T-cell lymphoma.
## Causes
The cause of Sézary syndrome is unknown. Most affected individuals have one or more chromosomal abnormalities, such as the loss or gain of genetic material. These abnormalities occur during a person's lifetime and are found only in the DNA of cancerous cells. Abnormalities have been found on most chromosomes, but some regions are more commonly affected than others. People with this condition tend to have losses of DNA from regions of chromosomes 10 and 17 or additions of DNA to regions of chromosomes 8 and 17. It is unclear whether these alterations play a role in Sézary syndrome, although the tendency to acquire chromosomal abnormalities (chromosomal instability) is a feature of many cancers. It can lead to genetic changes that allow cells to grow and divide uncontrollably.
## Inheritance Pattern
The inheritance pattern of Sézary syndrome has not been determined. This condition occurs in people with no history of the disorder in their family and is not thought to be inherited in most cases.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Sézary syndrome
|
c0026948
| 7,306 |
medlineplus
|
https://medlineplus.gov/genetics/condition/sezary-syndrome/
| 2021-01-27T08:24:36 |
{"gard": ["7629"], "mesh": ["D009182"], "omim": ["254400"], "synonyms": []}
|
A number sign (#) is used with this entry because of evidence that Doyne honeycomb retinal dystrophy is caused in a majority of cases by mutations in the EFEMP1 gene (601548) on chromosome 2p16.
Clinical Features
Characteristically small round white spots (drusen) involving the posterior pole of the eye, including the areas of the macula and optic disc, appear in early adult life. Progression to form a mosaic pattern which Doyne (1899) aptly termed 'honeycomb' occurs thereafter. Doyne considered it to represent 'choroiditis.' However, Collins (1913) showed that the changes consisted of swelling in the inner part of Bruch membrane. Failing vision usually developed considerably later than the ophthalmologic change. Robert Walter Doyne (1857-1916) was an ophthalmologist in Oxford, England. Pearce (1967) did an extensive study of 6 kindreds living near Oxford. Some and possibly all may have been descendants from a common ancestor. Dominant inheritance with complete manifestation of the trait in persons surviving beyond early adult life was found. Families living elsewhere than England have been reported (see references given by Pearce, 1968).
Hutchinson and Tay (1875) gave one of the first descriptions of the constellation of clinical findings later known as age-related macular degeneration. Three of the 10 patients they described were sisters affected with whitish spots (drusen) in the macula. Doyne (1899) reported a similar disorder in which the abnormal spots were nearly confluent, such that the macula had a 'honeycomb' appearance. Collins (1913) described histopathologic findings indicating that the abnormality in one of Doyne's patients consisted of hyaline thickenings of Bruch membrane. Vogt (1925) published the first description of the ophthalmoscopic appearance of a form of familial drusen that had been observed in patients living in the Leventine valley in the Ticino canton of southern Switzerland. The autosomal dominant inheritance was established. Waardenburg (1948) concluded there was little reason to make a distinction between malattia leventinese and the condition described by Doyne (1899). Forni and Babel (1962) found that the histopathologic features of leventinese disease are indistinguishable from those of Doyne honeycomb choroiditis.
Piguet et al. (1995) pointed out that the drusen in families with malattia leventinese are frequently distributed in a radial pattern. Although it is unknown what fraction of late-onset macular degeneration is caused by the gene or genes involved in malattia leventinese or Doyne disease, the clinical and histopathologic features suggest the diagnosis of age-related macular dystrophy.
Gregory et al. (1996) noted that Doyne honeycomb retinal dystrophy (DHRD) and malattia leventinese are both characterized by drusen. They cited reports describing the lesions of malattia leventinese as small discrete drusen which radiate into the peripheral retina; later, confluent soft drusen develop at the macula. Histopathologic studies established that the radial deposits are continuous with or internal to the basement membrane of the retinal pigment epithelium. In DRHD, large soft drusen deposits affecting the macula and peridiscal areas are seen. Histologically these deposits are external to the basement membrane of the retinal pigment epithelium and occupy the entire thickness of the Bruch membrane. Radial drusen extending into the periphery have not been found in DHRD.
Zech et al. (1999) provided a 25-year follow-up of a woman diagnosed with malattia leventinese at the age of 30 years. At that time, her vision was 20/20. Eight years later, subfoveal neovascularization led to an irreversible decrease in visual acuity in her right eye, down to 20/1,000. Twenty-three years later, a dense right vitreous hemorrhage led to a further decrease in visual acuity. At that time, the left eye had a visual acuity of 20/30, and fundus examination revealed a macula identical to that of the right eye, without complication.
Fu et al. (2007) studied a consanguineous Indian family in which a mother and father and their 2 sons had macular degeneration. The 2 sons exhibited significantly more severe phenotypes than either parent, particularly the older son whose retina demonstrated drusen extending beyond the posterior pole, with associated retinal degeneration.
Clinical Management
Both forms of dominant drusen (malattia leventinese and Doyne retinal degeneration) are characterized by slowly progressive loss of central visual acuity. However, the clinical course may change to one of very rapid progression and severe visual loss if choroidal neovascularization invades the subretinal space. Dantas et al. (2002) found that photodynamic therapy using verteporfin closed the neovascular membrane and prevented severe visual loss. They proposed that photodynamic therapy be considered as a possible treatment in patients with malattia leventinese who develop classic choroidal neovascularization.
Nicolo et al. (2003) assayed surgically-excised human choroidal neovascular membranes for the fibronectin isoform containing extradomain B, a marker-protein for angiogenesis, to determine whether it could be used as a therapeutic target for specific antibody-photosensitizer immunoconjugates. They found that extradomain B was abundantly expressed in choroidal neovascular membranes and were hopeful it could be used to enhance the selectivity of photodynamic therapy for newly developed vessels.
Mapping
Heon et al. (1996) demonstrated linkage of the autosomal dominant radial drusen (malattia leventinese) to DNA markers from 2p21-p16. They studied a large American kindred with 2 extensively affected branches and 3 kindreds from the Leventine valley. The maximum 2-point lod score observed for all 4 families combined was 10.5 and was obtained with the marker D2S378. Multipoint analysis yielded a maximum lod score of 12 centered on this same marker. The disease interval defined by observed recombinants was 14 cM. Heon et al. (1996) pointed out that beta-fodrin (182790) maps to 2p21 and is a promising candidate for the site of the mutation in this disorder.
Gregory et al. (1996) genotyped 9 markers in members of the DHRD pedigree originally described by Doyne (1910) and Pearce (1968) and established linkage to chromosome 2p. Haplotypes across the linked region were constructed for all family members and analysis of recombinants localized the DHRD gene to a 5-cM interval between D2S2316 and D2S378. These results established that DHRD maps to chromosome 2p16. Gregory et al. (1996) noted that the 14-kb region to which the malattia leventinese locus was mapped by Heon et al. (1996) encompasses the DHRD locus. They also stated that macular drusen are an important feature of age-related macular degeneration (ARMD; see 153800) and that the chromosome 2p21-p16 region should be considered as a candidate region for disease susceptibility in ARMD,
Kermani et al. (1999) used sequence tagged sites (STSs), expressed sequence tags (ESTs), and polymorphic markers within the DHRD region to identify 18 YACs encompassing the DHRD locus and spanning approximately 3 Mb. The YAC contig was constructed by STS content mapping of these YACs and incorporated 13 STSs, including 4 genes and 6 polymorphic marker loci. They also reported the genetic mapping of 2 families with a dominant drusen phenotype to the DHRD locus, and genetic refinement of the disease locus to a critical interval flanked by microsatellite marker loci D2S2352 and D2S2251, a distance of approximately 700 kb. These studies excluded a number of candidate genes and provided a resource for construction of a transcription map of the region, as a prerequisite for identification of the DHRD gene and genes for other diseases mapping in the region, such as malattia leventinese and Carney complex (160980).
Taymans et al. (1999) described radiation hybrid mapping of the region where both Carney complex and Doyne honeycomb retinal dystrophy map.
Molecular Genetics
In 5 families with Doyne honeycomb retinal dystrophy, Stone et al. (1999) found an arg345-to-trp (R345W; 601548.0001) mutation in the EFEMP1 gene. Matsumoto and Traboulsi (2001) reported a North American family with dominant radial drusen due to the R345W mutation in the EFEMP1 gene.
Tarttelin et al. (2001) identified the R345W mutation in the EFEMP1 gene (601548.0001) in 7 of 10 families with Doyne honeycomb retinal dystrophy and 1 of 17 sporadic patients. No other mutations were identified. Of the 3 families without an EFEMP1 mutation, 2 were linked to 2p16. Haplotype data in the family not linked to 2p16 suggested possible linkage to a locus at 6q14.
In a Swiss-Italian family in which 5 members in 3 generations had malattia leventinese, Toto et al. (2002) identified the R345W mutation in the EFEMP1 gene in 2. No mutation was identified in the EFEMP1 or the EFEMP2 gene in the other 3.
Fu et al. (2007) analyzed the EFEMP1 gene in a branch of 1 of the DHRD families originally described by Stone et al. (1999) and in a consanguineous Indian family with early-onset macular degeneration, and identified the R345W mutation in affected members of both families. The sons of the Indian family, who were more severely affected than their parents, were found to be homozygous for the mutation. The haplotype of the first family was identical to all previously reported haplotypes associated with the R345W mutation, whereas the disease haplotype in the Indian family was distinctly different, suggesting that the mutation arose independently.
Animal Model
Fu et al. (2007) generated Efemp1-R345W knockin mice and observed the development of deposits of material between Bruch's membrane and the retinal pigment epithelium (RPE) that resembled basal deposits in patients with age-related macular degeneration. Evidence of complement activation was detected in the RPE and Bruch's membrane of the mutant mice. Fu et al. (2007) concluded that the R345W mutation in EFEMP1 is pathogenic, and suggested that alterations in the extracellular matrix may stimulate complement activation and represent a connection between these 2 etiologic factors in macular degeneration.
Eyes \- Honeycomb retinal degeneration \- Small round white retinal spots \- Failing vision Inheritance \- Autosomal dominant \- ? same as drusen of Bruch membrane ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
DOYNE HONEYCOMB RETINAL DYSTROPHY
|
c1832174
| 7,307 |
omim
|
https://www.omim.org/entry/126600
| 2019-09-22T16:42:10 |
{"doid": ["0060745"], "mesh": ["C535602"], "omim": ["126600"], "orphanet": ["75376"], "synonyms": ["Alternative titles", "DOYNE HONEYCOMB DEGENERATION OF RETINA"]}
|
German syndrome is an autosomal recessive arthrogryposis syndrome, described in 5 cases. Three of the four known families with affected children were Ashkenazi Jews. German syndrome is characterized by arthrogryposis, hypotonia-hypokinesia sequence, and lymphedema. Patients present distinct craniofacial appearance (tall forehead and ''carp''-shaped mouth, cleft palate), contractures, severe hypotonia manifesting as motor delay, and swallowing difficulties. The disease has a severe morbidity and mortality rate and survivors present a small stature, hypotonia, frequent upper respiratory infections, and psychomotor delay. There have been no further descriptions in the literature since 1987.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
German syndrome
|
c3887495
| 7,308 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2077
| 2021-01-23T18:41:52 |
{"mesh": ["C562543"], "omim": ["231080"], "umls": ["C3887495"], "icd-10": ["Q87.8"], "synonyms": ["Hypotonia-arthrogryposis-facial dysmorphism-lymphedema syndrome"]}
|
The examples and perspective in this article deal primarily with the United States and do not represent a worldwide view of the subject. You may improve this article, discuss the issue on the talk page, or create a new article, as appropriate. (April 2020) (Learn how and when to remove this template message)
Intact dilation and extractionIDX, intact D&X, et al.
Background
Abortion typeSurgical
First use1983
Gestation>16 weeks
Usage
United States0.17% (2000)
Infobox references
Intact dilation and extraction (D&X, IDX, intact D&E) is a surgical procedure that removes an intact fetus from the uterus. The procedure is used both after miscarriages and for abortions in the second and third trimesters of pregnancy.
It is also known as intact dilation and evacuation (D&E) and, in United States federal law, as partial-birth abortion. Partial-birth abortion is not an accepted medical term and is not used by abortion practitioners or the medical community at large.[1][2]
In 2000, although only 0.17% (2,232 of 1,313,000) of all abortions in the United States were performed using this procedure,[3] it developed into a focal point of the abortion debate. Intact D&E of a fetus with a heartbeat was outlawed in most cases by the 2003 federal Partial-Birth Abortion Ban Act, which was upheld by the United States Supreme Court in the case of Gonzales v. Carhart.[1][4]
## Contents
* 1 Indications
* 2 Procedure
* 2.1 Cervical preparation
* 2.2 Feticide
* 2.3 Removal of fetus and placenta
* 3 Recovery
* 4 Complications
* 5 Society and culture
* 5.1 United States politics
* 5.2 Controversy
* 5.3 Legality in the United States
* 5.3.1 Federal law
* 5.3.2 State law
* 5.3.3 Clinical response to legal bans on the procedure
* 5.4 In other countries
* 6 References
* 7 External links
* 7.1 Legal documents
* 7.2 Commentary
* 7.3 Other
## Indications[edit]
As with non-intact D&E or labor induction in the second trimester, the purpose of D&E is to end a pregnancy by removing the fetus and placenta. Patients who are experiencing a miscarriage or who have a fetus diagnosed with severe congenital anomalies may prefer an intact procedure to allow for viewing of the remains, grieving, and achieving closure.[4][5] In cases where an autopsy is requested, an intact procedure allows for a more complete examination of the body.
An intact D&E is also used in abortions to minimize the passage of instruments into the uterus, reducing the risk of trauma. It also reduces the risk of cervical lacerations that may be caused by the removal of bony parts from the uterus and the risk of retention of fetal parts in the uterus such as brain matter and tissue.[4]
## Procedure[edit]
As with non-intact D&E, intact D&E may be safely performed in freestanding clinics, ambulatory surgical centers, and in hospitals. Intra-operative pain control is usually dependent on the setting and patient characteristics but commonly involves local analgesia with either IV sedation or general anesthesia. Preoperative antibiotics are administered to reduce the risk of infection.[6] In cases where the woman is Rh-negative, Rho(D) immunoglobulin (RhoGam) is administered to prevent the risk of developing erythroblastosis fetalis (hemolytic disease of the newborn) in subsequent pregnancies.[5] Intact D&E is more feasible among women with higher parity, at higher gestational ages, and when cervical dilation is greater.[4] There are no absolute contraindications.
### Cervical preparation[edit]
The surgery is preceded by cervical preparation which may take several days. Osmotic dilators, natural or synthetic rods that absorb moisture from the cervix, are placed in the cervix and mechanically dilate the cervix over the course of hours to days. Misoprostol can be used to soften the cervix further. Intact D&E can only be performed with 2-5 centimeters of cervical dilation.[5]
### Feticide[edit]
Feticidal injection of digoxin or potassium chloride may be administered at the beginning of the procedure to allow for softening of the fetal bones or to comply with relevant laws in the physician's jurisdiction and the U.S. federal Partial-Birth Abortion Ban Act.[4] Umbilical cord transection can also be used to induce fetal demise prior to removal.[7]
### Removal of fetus and placenta[edit]
During the surgery, the fetus is removed from the uterus in the breech position. If the fetal presentation is not breech, forceps or manual manipulation can be used to turn it to a breech presentation while in the uterus (internal version).[8] The fetal skull is usually the largest part of the fetal body and its removal may require mechanical collapse if it is too large to fit through the cervical canal.[9] Decompression of the skull can be accomplished by incision and suction of the brain or by using forceps to collapse the skull.[4]
## Recovery[edit]
Recovery from an intact D&E is similar to recovery from a non-intact D&E. Postoperative pain is usually minimal and managed with NSAIDs. In cases of uterine atony and corresponding blood loss, methergine or misoprostol can be given to encourage uterine contraction and achieve hemostasis.[5] Patients who have recently undergone an intact D&E are monitored for signs of coagulopathy, uterine perforation, uterine atony, retained tissue, or hemorrhage.[4]
## Complications[edit]
The risks of intact D&E are similar to the risks of non-intact D&E and include postoperative infection, hemorrhage, or uterine injury. Overall, the complication rate is low, with rates of serious complications (those requiring blood transfusion, surgery, or hospital treatment) ranging from 0 per 1,000 cases to 2.94 per 1,000 cases. The rate of minor complications is approximately 50 in 1,000 (5%), the same as the minor complication rate for non-intact D&E; the rate of serious complications is higher in non-intact D&E.[4]
Data directly comparing the safety of non-intact to intact D&E are limited.[10] There is no difference in postoperative blood loss or major complications when compared to non-intact D&E.[10][11] There is no difference in risk of subsequent preterm delivery.[12][13] The risk of retained tissue is lower since the fetus is removed intact.[14]
In some cases, the physician may not be able to remove the fetus intact due to anatomical limitations. This may present a psychological problem for the patient who wishes to view the remains, or make a comprehensive autopsy impossible, precluding an accurate postmortem diagnosis of fetal anomalies.[4]
## Society and culture[edit]
This section may be unbalanced towards certain viewpoints. Please improve the article or discuss the issue on the talk page. (December 2019)
Anthropology
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### United States politics[edit]
The term "partial-birth abortion" is primarily used in political discourse—chiefly regarding the legality of abortion in the United States.[15] The term is not recognized as a medical term by the American Medical Association[16] nor the American College of Obstetricians and Gynecologists.[17] This term was first suggested in 1995 by Congressman Charles T. Canady, while developing the original proposed Partial-Birth Abortion Ban.[18][19] According to Keri Folmar, the lawyer responsible for the bill's language, the term was developed in early 1995 in a meeting among herself, Charles T. Canady, and National Right to Life Committee lobbyist Douglas Johnson.[20] Canady could not find this particular abortion practice named in any medical textbook, and therefore he and his aides named it.[21] "Partial-birth abortion" was first used in the media on 4 June 1995 in a Washington Times article covering the bill.[citation needed]
The signing of the Partial-Birth Abortion Ban Act
In the U.S., a federal statute defines "partial-birth abortion" as any abortion in which the life of the fetus is terminated after having been extracted from the mother's body to a point "past the navel [of the fetus]" or "in the case of head-first presentation, the entire fetal head is outside the body of the mother" at the time the life is terminated. The U.S. Supreme Court has held that the terms "partial-birth abortion" and "intact dilation and extraction" are basically synonymous.[22] However, there are cases where these overlapping terms do not coincide. For example, the intact D&E procedure may be used to remove a deceased fetus (e.g., due to a miscarriage or feticide) that is developed enough to require dilation of the cervix for its extraction.[23] Removing a dead fetus does not meet the federal legal definition of "partial-birth abortion," which specifies that partial live delivery must precede "the overt act, other than completion of delivery, that kills the partially delivered, living fetus."[24]
In addition to the federal ban, there have also been a number of state partial-birth abortion bans. There, courts have found that state legislation (rather than federal legislation) intended to ban "partial-birth abortions" could be interpreted to apply to some non-intact dilation and evacuation (D&E) procedures.[25] Non-intact D&E, though performed at similar gestational ages, is a fundamentally different procedure.
### Controversy[edit]
Intact D&E is a target of anti-abortion advocates who believe the procedure illustrates their contention that abortion, and especially late-term abortion, is the taking of a human life, and therefore both immoral and illegal. Critics consider the procedure to be infanticide,[26] a position that many in the anti-abortion movement extend to cover all abortions.[27] Some advocates, both for and against abortion rights, see the intact D&E issue as a central battleground in the wider abortion debate, attempting to set a legal precedent so as to either gradually reduce or gradually increase access to all abortion methods.[28]
Dr. Martin Haskell has called the intact D&E procedure "a quick, surgical outpatient method" for late second-trimester and early third-trimester abortions.[29] The Partial-Birth Abortion Ban Act of 2003 describes it as "a gruesome and inhumane procedure that is never medically necessary."[30]
According to a BBC report about the U.S. Supreme Court's decision in Gonzales v. Carhart, "government lawyers and others who favour the ban, have said there are alternative and more widely used procedures that are still legal - which involves dismembering the fetus in the uterus."[31] An article in Harper's magazine stated that, "Defending the Partial-Birth Abortion Ban... requires arguing to judges that pulling a fetus from a woman's body in dismembered pieces is legal, medically acceptable, and safe; but that pulling a fetus out intact, so that if the woman wishes the fetus can be wrapped in a blanket and handed to her, is appropriately punishable by a fine, or up to two years' imprisonment, or both."[20] Alternately, pro-life advocates frame the issue as one in which a partially-born infant's life is disposable, whereas pulling the infant only a few more inches down the birth canal automatically transforms it into "a living person, possessing rights and deserving of protection."[32] The U.S. Supreme Court has stated that intact D&E remains legal as long as there is first a feticidal injection while the fetus is still completely inside of the mother's body.[23]
There is also controversy about why this procedure is used. Although prominent defenders of the method asserted during 1995 and 1996 that it was used only or mostly in acute medical circumstances, lobbyist Ron Fitzsimmons, executive director of the National Coalition of Abortion Providers (a trade association of abortion providers), told The New York Times (February 26, 1997): "In the vast majority of cases, the procedure is performed on a healthy mother with a healthy fetus that is 20 weeks or more along."[33] Some prominent pro-life advocates quickly defended the accuracy of Fitzsimmons's statements,[34] whilst others condemned Fitzsimmons as self-serving.[35]
In support of the Partial-Birth Abortion Ban Act, a nurse who witnessed three intact D&E procedures found them deeply disturbing, and described one performed on a 26½-week fetus with Down syndrome in testimony before a Judiciary subcommittee of the US House of Representatives.[36]
A journalist observed three intact and two non-intact D&E procedures involving fetuses ranging from 19 to 23 weeks. She "watched for any signs of fetal distress, but ... [she] could see no response, no reflexive spasm, nothing. Whether this was a result of the anesthesia or an undeveloped fetal system for pain sensitivity, one thing was clear: There was no discernible response by the fetus."[37]
Abortion provider Warren Hern asserted in 2003 that "No peer-reviewed articles or case reports have ever been published describing anything such as 'partial-birth' abortion, 'Intact D&E' (for 'dilation and extraction'), or any of its synonyms."[38] Therefore, Hern expressed uncertainty about what all of these terms mean. The U.S. Supreme Court held in Gonzales v. Carhart that these terms of the federal statute are not vague because the statute specifically detailed the procedure being banned: it specified anatomical landmarks past which the fetus must not be delivered, and criminalized such a procedure only if an "overt" fatal act is performed on the fetus after "partial delivery."[22]
### Legality in the United States[edit]
Main article: Partial-Birth Abortion Ban Act
#### Federal law[edit]
Since 1995, led by Republicans in Congress, the U.S. House of Representatives and U.S. Senate have moved several times to pass measures banning the procedure. Congress passed two such measures by wide margins during Bill Clinton's presidency, but Clinton vetoed those bills in April 1996 and October 1997 on the grounds that they did not include health exceptions. Subsequent congressional attempts at overriding the veto were unsuccessful.
A major part of the legal battle over banning the procedure relates to health exceptions, which would permit the procedure in special circumstances. The 1973 Supreme Court decision Roe v. Wade, which declared many state-level abortion restrictions unconstitutional, allowed states to ban abortions of post-viable fetuses unless an abortion was "necessary to preserve the life or health of the mother." The companion ruling, Doe v. Bolton, upheld against a vagueness challenge a state law that defined health to include mental as well as physical health. The Court has never explicitly held, as a matter of constitutional law, that states have to allow abortions of post-viable fetuses if doing so is necessary for the woman's mental health, but many read Doe as implying as much. The concern that the health exception can be read so liberally partly explains why supporters of the Partial-Birth Abortion Ban Act did not want to include one.
In 2003, the Partial-Birth Abortion Ban Act (H.R. 760, S. 3) was signed into law; the House passed it on October 2 with a vote of 281–142, the Senate passed it on October 21 with a vote of 64–34, and President George W. Bush signed it into law on November 5.
Beginning in early 2004, the Planned Parenthood Federation of America, the National Abortion Federation, and abortion doctors in Nebraska challenged the ban in federal district courts in the Northern District of California, Southern District of New York, and District of Nebraska. All three district courts ruled the ban unconstitutional that same year. Their respective federal courts of appeals—the Ninth Circuit, Second Circuit, and Eighth Circuit, respectively—affirmed these rulings on appeal.
The three cases were all appealed to the U.S. Supreme Court, and were consolidated into the case Gonzales v. Carhart. On April 18, 2007, the Supreme Court voted to uphold the Partial-Birth Abortion Ban Act by a decision of 5–4.[39] Justice Kennedy wrote for the majority and was joined by Justices Thomas, Scalia, Alito, and Chief Justice Roberts. A dissenting opinion was written by Justice Ginsburg and joined by Justices Stevens, Souter and Breyer.
#### State law[edit]
Many states have bans on late-term abortions which apply to intact D&E if it is performed after viability.
Many states have also passed bans specifically on intact D&E. The first was Ohio, which in 1995 enacted a law that referred to the procedure as dilation and extraction. In 1997, the United States Court of Appeals for the Sixth Circuit found the law unconstitutional on the grounds that it placed a substantial and unconstitutional obstacle in the path of women seeking pre-viability abortions in the second trimester.
Between 1995 and 2000, 28 more states passed Partial-Birth Abortion bans, all similar to the proposed federal bans and all lacking an exemption for the health of the woman. Many of these state laws faced legal challenges, with Nebraska's the first to reach decision in Stenberg v. Carhart. The Federal District Court held Nebraska's statute unconstitutional on two counts. One being the bill's language was too broad, potentially rendering a range of abortion procedures illegal, and thus, creating an undue burden on a woman's ability to choose. The other count was the bill failed to provide a necessary exception for the health of the woman. The decision was appealed to and affirmed by both the Eighth Circuit and the Supreme Court in June 2000, thus resolving the legal challenges to similar state bans nationwide.
Since the Stenberg v. Carhart decision, Virginia, Michigan, and Utah have adopted legislation very similar to the Nebraska law overturned as unconstitutional. The Michigan law was similarly struck down for broadness and failure to provide a health exemption. Utah's law remains on the books, pending trial, but is unenforceable under a court-ordered preliminary injunction. Virginia's Law was initially ruled invalid, but was reversed and remanded to the District Court in the wake of the Gonzales v. Carhart decision, where it was upheld as constitutional. This is despite the fact the Virginia law criminalizes abortions for accidental or intentional intact D&E.
In 2000 Ohio introduced another "partial-birth abortion" ban. The law differed from previous attempts at the ban in that it specifically excluded D&E procedures, while also providing a narrow health exception. This law was upheld on appeal to the Sixth Circuit in 2003 on the grounds that "it permitted the partial birth procedure when necessary to prevent significant health risks."
In 2003 the Michigan Senate introduced Senate Bill No. 395, which would have changed the definition of birth and therefore effectively ban intact D&E. would in effect ban partial birth abortions. The definition of birth as defined in the bill was that once any part of the body had passed beyond the introitus, it is considered a birth. The bill included an exemption for the mother's health. The bill was passed by both the Senate and House of Representatives but was vetoed by governor Jennifer Granholm.[citation needed]
#### Clinical response to legal bans on the procedure[edit]
Since the passage of the Partial-Birth Abortion Ban Act in the United States and similar state laws, providers of later abortions typically induce and document fetal death before beginning any later abortion procedure. Since the bans only apply to abortions of living fetuses, this protects the abortion providers from prosecution. The most common method of inducing fetal demise is to inject digoxin intrafetally or potassium chloride intrathoracically.[5][40]
### In other countries[edit]
Questioned about the policy of the UK government on the issue in Parliament, Baroness Andrews stated that
> We are not aware of the procedure referred to as "partial-birth abortion" being used in Great Britain. It is the Royal College of Obstetricians and Gynaecologists' (RCOG) belief that this method of abortion is never used as a primary or pro-active technique and is only ever likely to be performed in unforeseen circumstances in order to reduce maternal mortality or severe morbidity.[41]
## References[edit]
1. ^ a b Gonzales v. Carhart, 550 U.S. ____ (2007). Findlaw.com. Retrieved 2007-04-30.
2. ^ Oliveri, Rigel (2008). The Reproductive Rights Reader. New York University Press. p. 181.
3. ^ Guttmacher.org Abortion Incidence and Services in the United States in 2000
4. ^ a b c d e f g h i Paul, Maureen; Lichtenberg, Steve; Borgatta, Lynn; Grimes, David A.; Stubblefield, Phillip G.; Creinin, Mitchell D. (2011). Management of Unintended and Abnormal Pregnancy. John Wiley and Sons.
5. ^ a b c d e Gibbs, Ronald S. (2008). Danforth's Obstetrics and Gynecology. Lippincott Williams and Wilkins. ISBN 978-0-7817-6937-2.
6. ^ Paul, Maureen; Lichtenberg, Steve; Borgatta, Lynn; Grimes, David A.; Stubblefield, Phillip G.; Creinin, Mitchell D. (2011). Management of Unintended and Abnormal Pregnancy. John Wiley and Sons.
7. ^ Tocce, Kristina; Leach, Kara K.; Sheeder, Jeanelle L.; Nielson, Kandice; Teal, Stephanie B. (2013-08-08). "Umbilical cord transection to induce fetal demise prior to second-trimester D&E abortion". Contraception. 88 (6): 712–716. doi:10.1016/j.contraception.2013.08.001. ISSN 1879-0518. PMID 24034582.
8. ^ Paul, Maureen; Lichtenberg, Steve; Borgatta, Lynn; Grimes, David A.; Stubblefield, Phillip G.; Creinin, Mitchell D. (2011). Management of Unintended and Abnormal Pregnancy. John Wiley and Sons.
9. ^ Gibbs, Ronald S. (2008). Danforth's Obstetrics and Gynecology. Lippincott Williams and Wilkins. ISBN 978-0-7817-6937-2.
10. ^ a b Prager, Sarah Ward; Oyer, Deborah Jean (2009). "Second-trimester surgical abortion". Clinical Obstetrics and Gynecology. 52 (2): 179–187. doi:10.1097/GRF.0b013e3181a2b43a. ISSN 1532-5520. PMID 19407524. S2CID 6805714.
11. ^ Chasen, Stephen T.; Kalish, Robin B.; Gupta, Meruka; Kaufman, Jane E.; Rashbaum, William K.; Chervenak, Frank A. (2004). "Dilation and evacuation at >or=20 weeks: comparison of operative techniques". American Journal of Obstetrics and Gynecology. 190 (5): 1180–1183. doi:10.1016/j.ajog.2003.12.034. ISSN 0002-9378. PMID 15167815.
12. ^ Chasen, Stephen T.; Kalish, Robin B.; Gupta, Meruka; Kaufman, Jane; Chervenak, Frank A. (2005). "Obstetric outcomes after surgical abortion at > or = 20 weeks' gestation". American Journal of Obstetrics and Gynecology. 193 (3 Pt 2): 1161–1164. doi:10.1016/j.ajog.2005.05.078. ISSN 0002-9378. PMID 16157130.
13. ^ Chasen, Stephen T.; Kalish, Robin B.; Gupta, Meruka; Kaufman, Jane E.; Rashbaum, William K.; Chervenak, Frank A. (2004). "Dilation and evacuation at >or=20 weeks: comparison of operative techniques". American Journal of Obstetrics and Gynecology. 190 (5): 1180–1183. doi:10.1016/j.ajog.2003.12.034. ISSN 0002-9378. PMID 15167815.
14. ^ Paul, Maureen; Lichtenberg, Steve; Borgatta, Lynn; Grimes, David A.; Stubblefield, Phillip G.; Creinin, Mitchell D. (2011). Management of Unintended and Abnormal Pregnancy. John Wiley and Sons.
15. ^ D & X/PBA Procedures: Introduction. religioustolerance.org. Accessed April 14, 2006.
16. ^ Health and Ethics Policies of the AMA American Medical Association. H-5.982 Retrieved April 24, 2007.
17. ^ ACOG Files Amicus Brief in Gonzales v. Carhart and Gonzales v. PPFA September 22, 2006 The American College of Obstetricians and Gynecologists. Retrieved April 25, 2007.
18. ^ Alex Gordon. "The Partial-Birth Abortion Ban Act of 2003". Harvard Journal on Legislation. Volume 41, Number 2, Summer 2004. (see footnote 15)
19. ^ H.R.1833. To amend title 18, United States Code, to ban partial-birth abortions.
20. ^ a b Gorney, Cynthia. Gambling With Abortion. Harper's Magazine, November 2004.
21. ^ Adam Simon, “Elite Discourse, Programming and Survey Response in the Partial Birth Abortion Debate Archived 2007-06-14 at the Wayback Machine” (March 2003).
22. ^ a b Gonzales v. Carhart, 550 U.S. ____ (2007). Findlaw.com. Retrieved 2007-04-19.
23. ^ a b Gonzales v. Carhart, 550 U.S. ____ (2007). Findlaw.com. Retrieved 2007-04-30. ("If the intact D&E procedure is truly necessary in some circumstances, it appears likely an injection that kills the fetus is an alternative under the Act that allows the doctor to perform the procedure.")
24. ^ U.S. Code, Title 18, Part I, Chapter 74, Section 1531, "Partial-birth abortions prohibited."
25. ^ "American Civil Liberties Union :Abortion Bans: Myths and Facts". 28 November 2005. Archived from the original on 28 November 2005. Retrieved 4 April 2018.
26. ^ Koukl, Gregory. Partial-Birth Abortion Is Not About Abortion Archived 2007-09-27 at the Wayback Machine. Stand to Reason. Accessed April 25, 2006.
White, Deborah. Pros & Cons of Partial Birth Abortions About.com. Accessed April 25, 2006.
27. ^ The Official Point of View of the Romanian Orthodox Church on Abortion (summary) Archived 2006-05-13 at the Wayback Machine. The Romanian Patriarchate. Accessed April 25, 2006.
Achacoso, Jaime B. A Sin and a Crime Archived 2006-10-19 at the Wayback Machine Catholic.com. Accessed April 25, 2006.
Gonzalez, Ramon. Pro-life teens challenged Archived 2006-10-04 at the Wayback Machine Western Catholic Reporter. October 23, 2000. Accessed April 25, 2006.
28. ^ Slippery Slope: Democratic Wavering in the Battle for Reproductive Rights. PERRspectives.com. February 25, 2004. Accessed April 25, 2006.
Strategic Initiatives Archived 2006-10-13 at the Wayback Machine The Rockridge Institute. Accessed April 25, 2006.
29. ^ Haskell, Martin. Dilation and Extraction for Late Second Trimester Abortion. Presented at the National Abortion Federation Risk Management Seminar, September 13, 1992.
30. ^ 108th Congress, 1st Session, S.3. Partial Birth Abortion Ban Act of 2003.
31. ^ "US top court backs abortion ban". BBC. 2007-04-18. Retrieved 2007-04-18.
32. ^ "Fact #2: Every human being is a person. – AbortionFacts.com". www.abortionfacts.com. Retrieved 4 April 2018.
33. ^ Stout, David (1997-02-26). "An abortion rights advocate says he lied about procedure". The New York Times. p. A11. Retrieved 2009-06-08.
34. ^ Ruth Padawer, "Pro-choice advocates admit to deception" Archived 2007-06-14 at the Wayback Machine, Bergen Record, February 27, 1997.
35. ^ Melanie Conklin, "Whatever happened to the abortion lobbyist who repented?", The Progressive, September, 1997.
36. ^ Testimony of Brenda Pratt Shafer, R.N. Archived 2007-05-01 at the Wayback Machine Committee on the Judiciary, Subcommittee On The Constitution, U.S. House Of Representatives, March 21, 1996. Retrieved May 2, 2007.
37. ^ Woodbury, Margaret A. (2002-07-24). "A doctor's right to choose". Salon.com. Archived from the original on 2007-05-03. Retrieved 2007-04-29.
38. ^ Hern, Warren. "Did I Violate the Partial-Birth Abortion Ban?" (Slate, October 22, 2003).
39. ^ Sherman, Mark (April 18, 2007). "Court Backs ban on abortion procedure". SFGate. Archived from the original on November 14, 2007. Retrieved 2007-04-18.
40. ^ http://www.societyfp.org/_documents/resources/InductionofFetalDemise.pdf
41. ^ Text of a written answer to a parliamentary question at The House of Lords Hansard. Accessed 7 September 2006
## External links[edit]
### Legal documents[edit]
* Appeals court upholds Ohio "partial-birth abortion" law (AMANews article) : 19 January 2004.
* [permanent dead link] Appeals Court decision in Haskell v. Taft, upholding Ohio PBA Ban[permanent dead link] : (decided 17 December 2003) Includes description of the procedure, Decision of the Court, and Dissenting opinion
* Partial Birth Abortion Ban Act of 2003, signed by President Bush in March, 2003
* [permanent dead link] Ohio law banning "partial birth feticide"[permanent dead link] : enacted 18 August 2000.
* Stenberg v. Carhart Decision voiding Nebraska's PBA ban, circa 2000
* HR 1833, vetoed by President Clinton in 1996
* Congressional Testimony of Brenda Pratt Shafer, RN, March 21, 1996
### Commentary[edit]
* Ban Wagons – Reason Magazine article about the naming of "partial birth abortion" (supporting legality of the procedure)
* About.com's Pros & Cons of Partial Birth Abortion (neutral about the legality of the procedure)
* The Myth of Partial Birth Abortion, by Don Sloan, MD (supporting the legality of the procedure)[dead link]
* Partial-Birth Abortion – A Chink In The Pro-Abortion Armor (opposing the legality of the procedure)
* The "Partial-Birth" Myth – No, it's not a birth (supporting the legality of the procedure)[dead link]
* Gina Gonzales as told to Barry Yeoman, "I Had An Abortion When I Was Six Months Pregnant," Glamour (supporting the legality of the procedure)
### Other[edit]
* Martin Haskell's 1992 monograph: Dilation and Extraction for Late Second Trimester Abortion, which called the procedure "Dilation and Extraction"
* ReligiousTolerance.org: Dilation & Extraction (PBA) Procedure (aka Partial Birth Abortion) – All sides
* Presbyterians pro-life: A Pediatrician Looks at Babies Late in Pregnancy and Late Term Abortion
* A doctor's right to choose – Salon article
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|
Intact dilation and extraction
|
None
| 7,309 |
wikipedia
|
https://en.wikipedia.org/wiki/Intact_dilation_and_extraction
| 2021-01-18T18:57:38 |
{"wikidata": ["Q4165237"]}
|
## Clinical Features
Goeminne (1968) described an apparently novel X-linked trait with incomplete dominance. None of the affected males reproduced. Affected persons included (1) a male with congenital muscular torticollis; (2) a male with torticollis, cryptorchidism and varicose veins; (3) a male with torticollis, many spontaneous keloids, unilateral cryptorchidism, oligospermia, chronic pyelonephritis with unilateral renal atrophy, multiple cutaneous nevi, a basal cell epithelioma and varicose veins; (4) a male with torticollis, keloids and cryptorchidism; (5) a female with torticollis and pigmented nevi; and (6) a female with facial asymmetry, chronic pyelonephritis and nevi.
Fryns and Gevers (2003) stated that since the original report by Goeminne (1968) no similar patients had been reported. They presented similar distinct findings in a 17-year-old male of borderline intelligence who was the first and only child of healthy, unrelated parents. No evidence of genealogic connection between this family and the previously reported family was identified. Major clinical findings were (1) at birth, hypospadias-grade 2 and umbilical hernia; (2) at age 8 years, hyperkyphosis and pectus carinatum with short sternum; (3) at age 15 years, multiple keloids on the dorsum of the hands and forearms; (4) on clinical evaluation at age 17 years, distinct facial features, cutis verticis gyrata, hypogenitalism and peripheral hypogonadism, thin and translucent skin, and varicosities of the lower legs.
Mapping
Zuffardi and Fraccaro (1982) mapped the locus for this syndrome to Xq28, distal to G6PD (305900), based on reports they found in the literature of occurrence in 2 unrelated females with a balanced X-autosome translocation. In mouse-human cell hybrids containing the active der(X) chromosome from 1 of these patients, G6PD was expressed (Hellkuhl et al., 1982). Edwards (1982) pointed out that because of the disruption of genes that are located at the breakpoint on the X chromosome and because of the inactivation of the normal X chromosome in females with balanced X-autosome translocations, useful mapping information is provided by females with X/A translocations. Duchenne muscular dystrophy (310200) and Aicardi syndrome (304050) are disorders mapped by this method, and the Aarskog-Scott syndrome (305400) may be an example.
GU \- Cryptorchidism \- Renal dysplasia \- Oligospermia \- Chronic pyelonephritis \- Unilateral renal atrophy Neuro \- Torticollis Facies \- Facial asymmetry Inheritance \- X-linked with incomplete dominance (Xq28) Skin \- Keloids \- Pigmented nevi Vascular \- Varicose veins ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
TORTICOLLIS, KELOIDS, CRYPTORCHIDISM, AND RENAL DYSPLASIA
|
c1839129
| 7,310 |
omim
|
https://www.omim.org/entry/314300
| 2019-09-22T16:17:12 |
{"mesh": ["C536970"], "omim": ["314300"], "orphanet": ["3341"], "synonyms": ["Alternative titles", "TKC", "TKCR SYNDROME", "GOEMINNE SYNDROME"]}
|
A number sign (#) is used with this entry because autosomal recessive nonsyndromic mental retardation-15 (MRT15) is caused by homozygous mutation in the MAN1B1 gene (604346) on chromosome 9q34.
Clinical Features
Rafiq et al. (2010) reported 3 consanguineous Pakistani families with nonsyndromic mental retardation. The patients were severely mental retarded, all but 1 with an IQ less than 40 and all with delayed speech. Two of 3 sibs in 1 family had truncal obesity, and 2 other patients had epilepsy. None had microcephaly or autistic features. The families belonged to the same clan and were from the same village. Rafiq et al. (2011) provided follow-up of these families, who were from the Punjab province. Two patients had delayed psychomotor development and began walking at age 4 years. Both had hyperphagia and were overweight. Some patients achieved speaking in sentences and toilet training; aggression was a common feature. Mild dysmorphic features, such as dolichocephaly, downslanted palpebral fissures, broad nose, and small chin, were noted.
Rafiq et al. (2011) reported another consanguineous Pakistani family from the Sindh province with a similar, but less severe, form of intellectual disability. In addition to mental retardation, these patients showed dysmorphic features, including downslanting palpebral fissures, hypertelorism, long face, flattened malar region, short philtrum, broad nasal root, and small chin. Rafiq et al. (2011) also described 3 members of an Iranian family with nonsyndromic mental retardation. Overall intellectual disability varied, with 1 patient able to speak and count money and the others more severely affected. Seizures were variable. Dysmorphic features were mild and variable, but included dolichocephaly, long face, flat philtrum, downslanting palpebral fissures, hypertelorism, thin upper lip, triangular and pointed chin, and prominent nose.
Inheritance
The transmission pattern of mental retardation in the families reported by Rafiq et al. (2010) was consistent with autosomal recessive inheritance.
Mapping
By homozygosity mapping of 3 consanguineous Pakistani families with autosomal recessive nonsyndromic mental retardation, Rafiq et al. (2010) identified a locus, designated MRT15, on chromosome 9q34.4 (lod score of 4.8).
By homozygosity mapping of 2 consanguineous Iranian families with mild to moderate nonsyndromic mental retardation (families 8600060 and G015), Kuss et al. (2011) found linkage to a 2.5-Mb region on 9q34.3 (lod score of 3.1 and 3.3, respectively).
Molecular Genetics
In affected members of 5 families with autosomal recessive mental retardation-15, Rafiq et al. (2011) identified 3 different homozygous mutations in the MAN1B1 gene (604346.0001-604346.0003).
INHERITANCE \- Autosomal recessive GROWTH Weight \- Obesity (in 1 family) HEAD & NECK Head \- Dolichocephaly, mild Face \- Long face \- Flat philtrum \- Short philtrum \- Malar flattening \- Pointed chin \- Triangular chin Eyes \- Downslanting palpebral fissures \- Hypertelorism \- Broad eyebrows \- Long eyebrows Nose \- Broad nasal root \- Prominent nose Mouth \- Thin upper lip SKIN, NAILS, & HAIR Hair \- Broad eyebrows \- Long eyebrows NEUROLOGIC Central Nervous System \- Mental retardation, moderate to profound \- Delayed psychomotor development \- Seizures (variable) Behavioral Psychiatric Manifestations \- Aggressive behavior MISCELLANEOUS \- Dysmorphic features are variable MOLECULAR BASIS \- Caused by mutation in the mannosidase, alpha, class 1B, member 1 gene (MAN1B1, 604346.0001 ). ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
MENTAL RETARDATION, AUTOSOMAL RECESSIVE 15
|
c3280127
| 7,311 |
omim
|
https://www.omim.org/entry/614202
| 2019-09-22T15:56:09 |
{"doid": ["0050889"], "omim": ["614202"], "orphanet": ["88616"], "synonyms": ["AR-NSID", "NS-ARID"]}
|
Orofaciodigital syndrome type 13 is a rare subtype of orofaciodigital syndrome, with sporadic occurrence, characterized by cardiac (mitral and tricuspid valve dysplasia) and neuropsychiatric manifestations (epilepsy, depression), in addition to oral, facial and digital malformations (lingual hamartomas, cleft lip, brachydactyly, clinodactyly, syndactyly of hands and feet). Leukoaraiosis, on brain MRI examination, is also associated.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Orofaciodigital syndrome type 13
|
c2932680
| 7,312 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=141330
| 2021-01-23T18:57:51 |
{"gard": ["10694"], "mesh": ["C548035"], "umls": ["C2932680"], "icd-10": ["Q87.0"], "synonyms": ["Degner syndrome", "OFD13", "Oral-facial-digital syndrome type 13"]}
|
Fixed subaortic stenosis (FSS) is a rare heart malformation characterized by the obstruction by membranous or fibromuscular tissue of the left ventricular outflow tract (LVOT) below the aortic valve, that occurs as an isolated lesion or in association with additional cardiac malformations (e.g. ventricular septal defect, patent ductus arteriosus, coarctation of the aorta), that presents in childhood with signs of LVOT obstruction (e.g. dyspnea, chest pain, syncope, palpitations) and that can potentially lead to life-threatening complications (e.g. aortic regurgitation, infective endocarditis). It comprises three anatomical subforms: discrete fixed membranous subaortic stenosis (membranous tissue encircling the LVOT), discrete fibromuscular subaortic stenosis (fibromuscular tissue encircling the LVOT) and tunnel subaortic stenosis (fibromuscular diffuse tunnel-like narrowing of the LVOT), the two latter forms being generally more severe than the membranous form.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Fixed subaortic stenosis
|
c1848979
| 7,313 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3092
| 2021-01-23T18:16:30 |
{"mesh": ["C564793"], "omim": ["271950"], "umls": ["C1848979"], "icd-10": ["Q24.4"]}
|
Self-healing collodion baby (SHCB) is a minor variant of autosomal recessive congenital ichthyosis (ARCI; see this term) characterized by the presence of a collodion membrane at birth that heals within the first weeks of life.
## Epidemiology
The exact prevalence is unknown. Approximately 25 cases have been reported in the literature.
## Clinical description
Affected babies are born in a collodion membrane. They also display ectropion and eclabium and a limited joint mobility. After the shedding of the membrane, patients present with mild scaling.
## Etiology
SCHB is due to mutations in the TGM1, ALOXE3 or ALOX12B genes encoding respectively transglutaminase 1, involved in the cornification of the stratum corneum, and arachidonate 3 and 12(R) lipoxygenases involved in lipid metabolism. Transmission is autosomal recessive.
*[v]: View this template
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*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Self-improving collodion baby
|
c1855789
| 7,314 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=281122
| 2021-01-23T17:15:02 |
{"mesh": ["C565473"], "omim": ["242100", "242300", "606545"], "umls": ["C1855789"], "icd-10": ["Q80.2"], "synonyms": ["SHCB", "SICI", "Self-healing collodion baby", "Self-improving congenital ichthyosis"]}
|
A subtype of Metachromatic leukodystrophy characterized by progressive psychomotor regression with an onset between 30 months and 16 years of age, often beginning with behavioral abnormalities or deterioration of school performance. Further manifestations are ataxia, gait disturbances, reduced deep tendon reflexes, spasticity, seizures, paralysis, dementia, and loss of speech, vision, and hearing, eventually resulting in complete loss of motor and cognitive skills, and decerebration. The rate of deterioration is variable with possible survival up to the third decade of life.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Metachromatic leukodystrophy, juvenile form
|
c0751276
| 7,315 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=309263
| 2021-01-23T17:36:32 |
{"mesh": ["D007966"], "umls": ["C0751276"], "icd-10": ["E75.2"], "synonyms": ["Arylsulfatase A deficiency, juvenile form", "MLD, juvenile form"]}
|
Immature teratoma
Micrograph of the primitive neuroepithelium of an immature teratoma. H&E stain.
SpecialtyOncology
An immature teratoma is a teratoma that contains anaplastic immature elements, and is often synonymous with malignant teratoma.[1] A teratoma is a tumor of germ cell origin, containing tissues from more than one germ cell line,[2][3][4] It can be ovarian or testicular in its origin.[4] and are almost always benign.[5] An immature teratoma is thus a very rare tumor, representing 1% of all teratomas, 1% of all ovarian cancers, and 35.6% of malignant ovarian germ cell tumors.[6] It displays a specific age of incidence, occurring most frequently in the first two decades of life and almost never after menopause.[4] Unlike a mature cystic teratoma, an immature teratoma contains immature or embryonic structures. It can coexist with mature cystic teratomas and can constitute of a combination of both adult and embryonic tissue.[7][8] The most common symptoms noted are abdominal distension and masses.[9] Prognosis and treatment options vary and largely depend on grade, stage and karyotype of the tumor itself.
## Contents
* 1 Diagnosis
* 1.1 Stage
* 1.2 Pathology
* 1.3 Grade
* 1.4 Karyotype
* 2 Prognosis
* 3 Treatment
* 3.1 Surgery
* 3.2 Chemotherapy
* 4 See also
* 5 References
* 6 External links
## Diagnosis[edit]
At CT and MRI, an immature teratoma possesses characteristic appearance. It is typically large (12–25 cm) and has prominent solid components with cystic elements.[10] It is usually filled with lipid constituents and therefore demonstrates fat density at CT and MRI.[10] Ultrasound appearance of an immature teratoma is nonspecific. It is highly heterogeneous with partially solid lesions and scattered calcifications.[11][12]
### Stage[edit]
Traditionally, comprehensive surgical staging is performed via exploratory laparotomy with cytologic washings, peritoneal biopsies, an omental assessment (either biopsy or rarely a full omentectomy), and both pelvic and aortic lymph node dissection. Laproscopy is often suggested as an alternative to surgically stage patients with immature teratoma.[13][14]
Ovarian cancer is staged using the FIGO staging system and uses information obtained after surgery, which can include a total abdominal hysterectomy via midline laparotomy, unilateral (or bilateral) salpingo-oophorectomy, pelvic (peritoneal) washings, assessment of retroperitoneal lymph nodes and/or appendectomy.[15][16] The AJCC staging system, identical to the FIGO staging system, describes the extent of tumor (T), the presence of absences of metastases to lymph nodes (N), the presence or absence of distant metastases (M).[17]
Table 1: FIGO Staging System for Ovarian Cancers[16] Stage Description
I Cancer is completely limited to the ovary
IA involves one ovary, capsule intact, no tumor on ovarian surface, negative washings
IB involves both ovaries; capsule intact; no tumor on ovarian surface; negative washings
IC tumor involves one or both ovaries
IC1 surgical spill
IC2 capsule has ruptured or tumor on ovarian surface
IC3 positive ascites or washings
II pelvic extension of the tumor (must be confined to the pelvis) or primary peritoneal tumor, involves one or both ovaries
IIA tumor found on uterus or fallopian tubes
IIB tumor elsewhere in the pelvis
III cancer found outside the pelvis or in the retroperitoneal lymph nodes, involves one or both ovaries
IIIA metastasis in retroperitoneal lymph nodes or microscopic extrapelvic metastasis
IIIA1 metastasis in retroperitoneal lymph nodes
IIIA1(i) the metastasis is less than 10 mm in diameter
IIIA1(ii) the metastasis is greater than 10 mm in diameter
IIIA2 microscopic metastasis in the peritoneum, regardless of retroperitoneal lymph node status
IIIB metastasis in the peritoneum less than or equal to 2 cm in diameter, regardless of retroperitoneal lymph node status; or metastasis to liver or spleen capsule
IIIC metastasis in the peritoneum greater than 2 cm in diameter, regardless of retroperitoneal lymph node status; or metastasis to liver or spleen capsule
IV distant metastasis (i.e. outside of the peritoneum)
IVA pleural effusion containing cancer cells
IVB metastasis to distant organs (including the parenchyma of the spleen or liver), or metastasis to the inguinal and extra-abdominal lymph nodes
### Pathology[edit]
Ovarian tumors by incidence and risk of ovarian cancer, with immature teratoma at right.[18]
An immature teratoma contains varying compositions of adult and embryonic tissue. The most common embryonic component identified in immature teratomas is the neuroectoderm.[19] Occasionally, tumors may present neuroepithelium that resemble neuroblasts.[19] Tumors may also present embryonic components such as immature cartilage and skeletal muscle of mesodermal origin.[19] Immature teratomas composed of embryonic endodermal derivatives are rare.[19]
Often a mature cystic teratoma is misdiagnosed as its immature counterpart due to the misinterpretation of mature neural tissue as immature.[20] While mature neural cells have nuclei with uniformly dense chromatin and neither exhibit apoptotic or mitotic activity, immature neural cells have nuclei with vesicular chromatin and exhibit both apoptotic and mitotic activity.[20] A recent study has identified the use of Oct-4 as a reliable biomarker for the diagnosis of highly malignant cases of immature teratomas.[21]
### Grade[edit]
Thurlbeck and Scully devised a grading system for “pure” immature teratomas on the basis of differentiation of the cellular elements of the tumor.[22] The proportion of immature tissue elements defines the grade of immaturity.[22] This was later modified by Norris et al. (1976), who added a quantitative aspect to the degree of immaturity.[23]
Table 2: Identifying Tumor Grade in Immature Teratomas[22][23] Grade Thurlbeck and Scully (1960) Norris et al. (1976)
0 All cells are well differentiated All cells are mature; mitotic activity is rare or absent.
1 Cells are well differentiated except in rare small foci of embryonic tissue; neuroepithelium is absent or rare Neuroepithelium absent or limited to fewer than one low-magnification field (x40) per slide
2 Moderate quantities of embryonic tissue present; cells show atypicality and mitotic activity Neuroepithelium does not exceed more than three low-magnification fields (x40) per slide
3 Large quantities of embryonic tissue present; cells show atypicality and mitotic activity Neuroepithelium exceeds more than three low-magnification fields (x40) per slide
### Karyotype[edit]
An ovarian immature teratoma is karyotypically normal 46,XX or near-normal. Grade 1 or 2 tumors exhibit 46,XX normal karyotype, whereas grade 3 tumors show a variety of abnormal karyotypes.[24] Though immature teratoma cells show a normal karyotype, there may still be detectable alterations in the gene level and that these aberrations may influence the stability of chromosome status.[24]
## Prognosis[edit]
Though several studies have shown that size and stage of the primary tumor are related to survival, the grade of the tumor is the best determinant of prognosis prior to peritoneal spread.[23][24] Once peritoneal spread has occurred, the grade of metastatic lesions or implants is the best determinant of prognosis.[23][24] Multiple sections of the primary tumor and wide sampling of the implants are necessary to properly grade the tumor. In most cases, the implants are better differentiated than the primary tumors.[8] Gliomatosis peritonei, a rare condition often associated with immature ovarian teratoma, is characterized by the presence of mature glial implants in the peritoneum.[25] Yoon et al. (2012), reported that immature ovarian teratoma patients with Gliomatosis peritonei have larger tumors, more frequent recurrence and higher CA-125 levels than immature ovarian teratoma patients without gliomatosis peritonei.[26]
A high degree of immaturity in the primary tumor, one that corresponds with a grade 3 diagnosis is a sign of poor prognosis.[23][8][27][28] Grade 3 tumors often display chromosomal abnormalities, also an indication of poor prognosis.[24] Tumor grade is the most important factor for relapse in immature teratomas.[27] Vicus et al. (2011), reported that grade 2 or 3 tumors are associated with a greater chance of relapse that can be fatal, predominantly within 2 years of diagnosis.[29] Among grade 3 patients, the stage was significantly associated with relapse.[29]
In the past, survival rates were low for high-grade immature teratomas. Norris et al. (1976), reported a survival rate of 82% for patients with grade 1 tumors, 62% for grade 2 and 30% for grade 3 tumors.[23] However, these results antedate the use of multi-agent chemotherapy.[8] With the advent of multiagent chemotherapy after surgical resection, long-term remission and increased survival rates have been achieved. Pashankar et al. (2016), reported that the estimated 5-year overall survival rate for grade 3 Stage I and II disease was 91% compared with 88% for grade 3, Stage III and IV disease.[27]
## Treatment[edit]
Histologic grade and fertility desires of the patient are key considerations in determining treatment options. In adult women postoperative adjuvant chemotherapy is standard except for stage I /grade 1 disease. In pediatric patients, surgery alone is standard.[27]
### Surgery[edit]
Since the occurrence of immature teratoma is very rarely bilateral, current standard of care of unilateral salpingo-oophorectomy with wide sampling of peritoneal implants.[8] Total abdominal hysterectomy with bilateral salpingo-oophorectomy are not indicated as they do not influence outcomes.[8] Fertility-sparing surgery in the form of unilateral salpingo-oophorectomy is the primary treatment modality in young patients.[30][31][32] Some physicians recommend ovarian cystectomy alone, rather than a unilateral salpingo-oophorectomy for patients with an early stage low grade disease. Zhao et al. (2017), reported no significant differences in survival rates or post-operative fertility outcomes between the two treatment options.[33] However, others caution against such an approach.[8]
### Chemotherapy[edit]
Norris et al. (1976) observed an 18% recurrence rate in grade 2 tumors and 70% recurrence in grade 3 tumors.[23] Gershenson et al. (1986), reported outcomes of 41 patients with Stage I-IV disease and observed recurrences in 94% of patients treated with surgery alone compared with 14% in patients treated with surgery and chemotherapy.[34] Studies like these resulted in the recommendation to use chemotherapy for grade 2 and 3 tumors. Currently, the use of multi agent chemotherapy for adult patients with ovarian immature teratoma is standard of care except for grade 1, stage I tumors.[27] There is considerable experience with a combination of vincristine, dactinomycin, and cyclophosphamide (VAC) given in an adjuvant setting; however, combinations containing cisplatin, etoposide, and bleomycin (BEP) are now preferred because of a lower relapse rate and shorter treatment time.[35] While a prospective comparison of VAC versus BEP has not been performed, in well-staged patients with completely resected tumors, relapse is essentially unheard of following platinum-based chemotherapy.[35] However, the disease will recur in about 25% of well-staged patients treated with 6 months of VAC.[36]
## See also[edit]
* Teratoma
* Ovarian Cancer
* Germ Cell Tumor
## References[edit]
1. ^ Sun, Hang; Ding, Hongxin; Wang, Jianjun; Zhang, Emma; Fang, Yihua; Li, Zhenhua; Yu, Xiao; Wang, Chongren; Zhao, Yifan; Chen, Kan; Wen, Siwan; Li, Liang; Shan, Shan; Hong, Liu; Chen, Face; Su, Pu (2019). "The differences between gonadal and extra-gonadal malignant teratomas in both genders and the effects of chemotherapy". BMC Cancer. 19 (1). doi:10.1186/s12885-019-5598-0. ISSN 1471-2407.
2. ^ "NCI Dictionary of Cancer Terms". National Cancer Institute. 2011-02-02. Retrieved 2018-04-20.
3. ^ Damjanov, Ivan (2009). Pathology secrets (3rd ed.). Philadelphia, PA: Mosby/Elsevier. ISBN 9780323055949. OCLC 460883266.
4. ^ a b c Ulbright, Thomas M. (January 2004). "Gonadal teratomas: a review and speculation". Advances in Anatomic Pathology. 11 (1): 10–23. doi:10.1097/00125480-200401000-00002. ISSN 1072-4109. PMID 14676637.
5. ^ Schmidt, D.; Kommoss, F. (2007-05-01). "Teratome des Ovars". Der Pathologe (in German). 28 (3): 203–208. doi:10.1007/s00292-007-0909-7. ISSN 0172-8113. PMID 17396268.
6. ^ Alwazzan, Ahmad Bakr; Popowich, Shaundra; Dean, Erin; Robinson, Christine; Lotocki, Robert; Altman, Alon D. (November 2015). "Pure Immature Teratoma of the Ovary in Adults". International Journal of Gynecological Cancer. 25 (9): 1616–1622. doi:10.1097/IGC.0000000000000541. ISSN 1048-891X. PMC 4623850. PMID 26332392.
7. ^ Coran, Arnold G.; Adzick, N. Scott (2012). Pediatric surgery (7th ed.). Philadelphia, PA: Elsevier Mosby. pp. 539–548. ISBN 9780323072557. OCLC 778785699.
8. ^ a b c d e f g Di Saia, Philip J.; Creasman, William T.; Di Saia, Philip J. (2012). Clinical gynecologic oncology (8th ed.). Philadelphia, PA: Elsevier/Saunders. pp. 329–356. ISBN 9780323074193. OCLC 785577276.
9. ^ Ki, Eun Young; Byun, Seung Won; Choi, Yoon Jin; Lee, Keun Ho; Park, Jong Sup; Lee, Sung Jong; Hur, Soo Young (2013-06-21). "Clinicopathologic Review of Ovarian Masses in Korean Premenarchal Girls". International Journal of Medical Sciences. 10 (8): 1061–1067. doi:10.7150/ijms.6216. ISSN 1449-1907. PMC 3691806. PMID 23801894.
10. ^ a b Malkasian, G. D.; Symmonds, R. E.; Dockerty, M. B. (June 1965). "Malignant ovarina teratomas. Report of 31 cases". Obstetrics and Gynecology. 25: 810–814. ISSN 0029-7844. PMID 14287472.
11. ^ Brammer, H. M.; Buck, J. L.; Hayes, W. S.; Sheth, S.; Tavassoli, F. A. (July 1990). "From the archives of the AFIP. Malignant germ cell tumors of the ovary: radiologic-pathologic correlation". RadioGraphics. 10 (4): 715–724. doi:10.1148/radiographics.10.4.2165627. ISSN 0271-5333. PMID 2165627.
12. ^ Moş, Călin (2009). "Ovarian dermoid cysts: ultrasonographic findings" (PDF). Pictorial Essay Medical Ultrasonography. 11: 61–66.
13. ^ Nishida, Masakazu; Kawano, Yasushi; Yuge, Akitoshi; Nasu, Kaei; Matsumoto, Harunobu; Narahara, Hisashi (2014-09-03). "Three Cases of Immature Teratoma Diagnosed after Laparoscopic Operation". Clinical Medicine Insights: Case Reports. 7: 91–94. doi:10.4137/CCRep.S17455. ISSN 1179-5476. PMC 4159361. PMID 25232281.
14. ^ Brown, Kaessee L.; Barnett, Jason C.; Leath, Charles A. (2015-03-01). "Laparoscopic Staging of Ovarian Immature Teratomas: A Report on Three Cases". Military Medicine. 180 (3): e365–e368. doi:10.7205/milmed-d-14-00288. ISSN 0026-4075. PMID 25735031.
15. ^ Longo, Dan L. (2012). Harrison's principles of internal medicine (18th ed.). New York: McGraw-Hill. ISBN 9780071748896. OCLC 288932926.
16. ^ a b Jayson, Gordon C; Kohn, Elise C; Kitchener, Henry C; Ledermann, Jonathan A (2014-10-11). "Ovarian cancer". The Lancet. 384 (9951): 1376–1388. doi:10.1016/s0140-6736(13)62146-7. PMID 24767708.
17. ^ "How is Ovarian Cancer Staged?". American Cancer Society.
18. ^ \- Vaidya, SA; Kc, S; Sharma, P; Vaidya, S (2014). "Spectrum of ovarian tumors in a referral hospital in Nepal". Journal of Pathology of Nepal. 4 (7): 539–543. doi:10.3126/jpn.v4i7.10295. ISSN 2091-0908.
\- Minor adjustment for mature cystic teratomas (0.17 to 2% risk of ovarian cancer): Mandal, Shramana; Badhe, Bhawana A. (2012). "Malignant Transformation in a Mature Teratoma with Metastatic Deposits in the Omentum: A Case Report". Case Reports in Pathology. 2012: 1–3. doi:10.1155/2012/568062. ISSN 2090-6781.
19. ^ a b c d Weidner, Noel (2009). Modern surgical pathology (2nd ed.). Philadelphia, PA: Saunders/Elsevier. ISBN 9781416039662. OCLC 460883320.
20. ^ a b Nucci, Marisa R.; Oliva, Esther (2009). Gynecologic pathology : a volume in the series foundations in diagnostic pathology. Edinburgh: Churchill Livingstone/Elservier. pp. 501–538. ISBN 9780443069208. OCLC 460883296.
21. ^ Abiko, Kaoru; Mandai, Masaki; Hamanishi, Junzo; Matsumura, Noriomi; Baba, Tsukasa; Horiuchi, Akiko; Mikami, Yoshiki; Yoshioka, Shinya; Wakasa, Tomoko (December 2010). "Oct4 expression in immature teratoma of the ovary: relevance to histologic grade and degree of differentiation". The American Journal of Surgical Pathology. 34 (12): 1842–1848. doi:10.1097/PAS.0b013e3181fcd707. ISSN 1532-0979. PMID 21107090.
22. ^ a b c Thurlbeck, W. M.; Scully, R. E. (July 1960). "Solid teratoma of the ovary. A clinicopathological analysis of 9 cases". Cancer. 13 (4): 804–811. doi:10.1002/1097-0142(196007/08)13:4<804::AID-CNCR2820130423>3.0.CO;2-V. ISSN 0008-543X. PMID 13838271.
23. ^ a b c d e f g Norris, H. J.; Zirkin, H. J.; Benson, W. L. (May 1976). "Immature (malignant) teratoma of the ovary: a clinical and pathologic study of 58 cases". Cancer. 37 (5): 2359–2372. doi:10.1002/1097-0142(197605)37:5<2359::AID-CNCR2820370528>3.0.CO;2-Q. ISSN 0008-543X. PMID 1260722.
24. ^ a b c d e Ihara, T.; Ohama, K.; Satoh, H.; Fujii, T.; Nomura, K.; Fujiwara, A. (1984-12-15). "Histologic grade and karyotype of immature teratoma of the ovary". Cancer. 54 (12): 2988–2994. doi:10.1002/1097-0142(19841215)54:12<2988::AID-CNCR2820541229>3.0.CO;2-U. ISSN 0008-543X. PMID 6498772.
25. ^ Liang, Li; Zhang, Yifen; Malpica, Anais; Ramalingam, Preetha; Euscher, Elizabeth D.; Fuller, Gregory N.; Liu, Jinsong (December 2015). "Gliomatosis peritonei: a clinicopathologic and immunohistochemical study of 21 cases". Modern Pathology. 28 (12): 1613–1620. doi:10.1038/modpathol.2015.116. ISSN 0893-3952. PMC 4682736. PMID 26564007.
26. ^ Yoon, Na Ra; Lee, Jeong-Won; Kim, Byoung-Gie; Bae, Duk-Soo; Sohn, Insuk; Sung, Chang Ohk; Song, Sang Yong (2012-09-01). "Gliomatosis peritonei is associated with frequent recurrence, but does not affect overall survival in patients with ovarian immature teratoma". Virchows Archiv. 461 (3): 299–304. doi:10.1007/s00428-012-1285-0. ISSN 0945-6317. PMID 22820986.
27. ^ a b c d e Pashankar, Farzana; Hale, Juliet P.; Dang, Ha; Krailo, Mark; Brady, William E.; Rodriguez-Galindo, Carlos; Nicholson, James C.; Murray, Matthew J.; Bilmire, Deborah F. (2016-01-15). "Is Adjuvant Chemotherapy Indicated in Ovarian Immature Teratomas? A Combined Data Analysis From the Malignant Germ Cell Tumor International Collaborative". Cancer. 122 (2): 230–237. doi:10.1002/cncr.29732. ISSN 0008-543X. PMC 5134834. PMID 26485622.
28. ^ Nogales, F. F.; Favara, B. E.; Major, F. J.; Silverberg, S. G. (November 1976). "Immature teratoma of the ovary with a neural component ("solid" teratoma). A clinicopathologic study of 20 cases". Human Pathology. 7 (6): 625–642. doi:10.1016/S0046-8177(76)80076-7. ISSN 0046-8177. PMID 992645.
29. ^ a b Vicus, Danielle; Beiner, Mario E.; Clarke, Blaise; Klachook, Shany; Le, Lisa W.; Laframboise, Stephane; Mackay, Helen (October 2011). "Ovarian immature teratoma: treatment and outcome in a single institutional cohort". Gynecologic Oncology. 123 (1): 50–53. doi:10.1016/j.ygyno.2011.06.037. ISSN 1095-6859. PMID 21764111.
30. ^ Tay, S.-K.; Tan, L.-K. (January 2000). "Experience of a 2-day BEP regimen in postsurgical adjuvant chemotherapy of ovarian germ cell tumors". International Journal of Gynecological Cancer. 10 (1): 13–18. doi:10.1046/j.1525-1438.2000.00010.x. ISSN 1525-1438. PMID 11240646.
31. ^ Kanazawa, K.; Suzuki, T.; Sakumoto, K. (June 2000). "Treatment of malignant ovarian germ cell tumors with preservation of fertility: reproductive performance after persistent remission". American Journal of Clinical Oncology. 23 (3): 244–248. doi:10.1097/00000421-200006000-00007. ISSN 0277-3732. PMID 10857886.
32. ^ Low, J. J.; Perrin, L. C.; Crandon, A. J.; Hacker, N. F. (2000-07-15). "Conservative surgery to preserve ovarian function in patients with malignant ovarian germ cell tumors. A review of 74 cases". Cancer. 89 (2): 391–398. doi:10.1002/1097-0142(20000715)89:2<391::AID-CNCR26>3.0.CO;2-V. ISSN 0008-543X. PMID 10918171.
33. ^ Zhao, Ting; Liu, Yan; Wang, Xiao; Zhang, Hao; Lu, Yuan (April 2017). "Ovarian cystectomy in the treatment of apparent early-stage immature teratoma". The Journal of International Medical Research. 45 (2): 771–780. doi:10.1177/0300060517692149. ISSN 0300-0605. PMC 5536676. PMID 28415950.
34. ^ Gershenson, D. M.; del Junco, G.; Silva, E. G.; Copeland, L. J.; Wharton, J. T.; Rutledge, F. N. (November 1986). "Immature teratoma of the ovary". Obstetrics and Gynecology. 68 (5): 624–629. ISSN 0029-7844. PMID 3763073.
35. ^ a b Williams, S.; Blessing, J. A.; Liao, S. Y.; Ball, H.; Hanjani, P. (April 1994). "Adjuvant therapy of ovarian germ cell tumors with cisplatin, etoposide, and bleomycin: a trial of the Gynecologic Oncology Group". Journal of Clinical Oncology. 12 (4): 701–706. doi:10.1200/JCO.1994.12.4.701. ISSN 0732-183X. PMID 7512129.
36. ^ Slayton, R. E.; Park, R. C.; Silverberg, S. G.; Shingleton, H.; Creasman, W. T.; Blessing, J. A. (1985-07-15). "Vincristine, dactinomycin, and cyclophosphamide in the treatment of malignant germ cell tumors of the ovary. A Gynecologic Oncology Group Study (a final report)". Cancer. 56 (2): 243–248. doi:10.1002/1097-0142(19850715)56:2<243::AID-CNCR2820560206>3.0.CO;2-T. ISSN 0008-543X. PMID 2988740.
## External links[edit]
Classification
D
* Immature teratoma entry in the public domain NCI Dictionary of Cancer Terms
This article incorporates public domain material from the U.S. National Cancer Institute document: "Dictionary of Cancer Terms".
* v
* t
* e
Germ cell tumors
Germinomatous
* Germinoma
* Seminoma
* Dysgerminoma
Nongerminomatous
* Embryonal carcinoma
* Endodermal sinus tumor/Yolk sac tumor
* Teratoma: Fetus in fetu
* Dermoid cyst
* Struma ovarii
* Strumal carcinoid
* Trophoblastic neoplasm: Gestational trophoblastic disease
* Hydatidiform mole
* Choriocarcinoma
* Placental site trophoblastic tumor
* Polyembryoma
* Gonadoblastoma
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Immature teratoma
|
c0855163
| 7,316 |
wikipedia
|
https://en.wikipedia.org/wiki/Immature_teratoma
| 2021-01-18T18:44:00 |
{"umls": ["C0855163"], "wikidata": ["Q6004750"]}
|
Female infertility due to zona pellucida defect is a rare, genetic, female infertility disorder characterized by the presence of abnormal oocytes that lack a zona pellucida. Affected individuals are unable to conceive despite having normal menstrual cycles and sex hormone levels, as well as no obstructions in the fallopian tubes or defects of the uterus or adnexa.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Female infertility due to zona pellucida defect
|
c4014291
| 7,317 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=404466
| 2021-01-23T18:32:15 |
{"omim": ["615774", "617712", "618353"], "icd-10": ["N97.8"]}
|
## Description
Usher syndrome type I an autosomal recessive disorder characterized by profound congenital hearing impairment with unintelligible speech, early retinitis pigmentosa, and constant vestibular dysfunction (summary by Chaib et al., 1997).
For a discussion of genetic heterogeneity of USH type I, see 276900.
Mapping
Using homozygosity mapping in a consanguineous family in Morocco, Chaib et al. (1997) identified a genetically distinct form, which they called USH1E and mapped to 21q21. The delimited 15-cM interval was flanked by D21S1905 and D21S1913.
INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Hearing loss, congenital sensorineural \- Vestibular areflexia, complete Eyes \- Retinitis pigmentosa ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
USHER SYNDROME, TYPE IE
|
c0271097
| 7,318 |
omim
|
https://www.omim.org/entry/602097
| 2019-09-22T16:13:55 |
{"doid": ["0110833"], "mesh": ["D052245"], "omim": ["602097"], "orphanet": ["886", "231169"], "genereviews": ["NBK1265"]}
|
In lower vertebrates, a major function of prolactin (PRL) is to conserve water and maintain electrolyte balance. Studies in man and lower primates indicate that PRL also influences water and ion fluxes across the placental membranes, the amnion and chorion laeve, which are both of fetal origin and are apposed to maternal decidual tissue. PRL is secreted by human decidual cells and is present in amniotic fluid in high concentrations. Herington et al. (1980) demonstrated that high affinity, low capacity receptors for PRL and other lactogen hormones such as growth hormone exist in human chorion laeve. Healy et al. (1983) reasoned that chronic idiopathic polyhydramnios might be due to a defect in these receptors. (Idiopathic or primary polyhydramnios is the most numerous category in most series of chronic polyhydramnios. Other associations are diabetes mellitus, multiple pregnancy, rhesus isoimmunization, fetal malformations, and placental neoplasms.) Healy et al. (1983) found reduced specific binding of growth hormone to chorion laeve. Scatchard analysis was consistent with a reduced lactogen hormone receptor concentration. Specific binding of insulin was normal. Information on familial aggregation of this complication of pregnancy will be of interest. Healy (1983) indicated that he had 'been intrigued by the possible inheritance of this obstetric complication' but had no data bearing on the question from his studies in Australia and Ireland.
Misc \- Chronic idiopathic polyhydramnios Lab \- Chorionic lactogen receptor defect \- Normal specific insulin binding Inheritance \- ? Autosomal recessive ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
POLYHYDRAMNIOS, CHRONIC IDIOPATHIC
|
c1849720
| 7,319 |
omim
|
https://www.omim.org/entry/263610
| 2019-09-22T16:23:14 |
{"mesh": ["C564876"], "omim": ["263610"], "synonyms": ["Alternative titles", "LACTOGEN RECEPTOR DEFECT OF CHORION"]}
|
## Description
Pathologic gambling is defined as a chronic and progressive failure to resist impulses to gamble accompanied by gambling behavior that compromises or damages personal, family, or vocational pursuits. The prevalence of pathologic gambling in the adult American population is estimated to be between 1 and 3% (review by Eisen et al., 1998).
Comings et al. (2001) noted that some form of gambling is legal in all but 2 states in the U.S., and gambling on the Internet is available to anyone with a computer regardless of the local laws. They stated that as access to gambling has increased, there has been a corresponding increase in the frequency of addiction to gambling, known as pathologic gambling.
Inheritance
Eisen et al. (1997, 1998) studied 3,359 mono- and dizygotic U.S. male twin pairs who had served in the military and found that inherited factors explained between 37 and 55% of the prevalence of 5 individual symptoms of pathologic gambling (attempts to wind back losses at same place, gambling larger amounts than intended, repeated efforts to reduce or stop gambling, frequent preoccupation with gambling, and increase betting to maintain interest) from DSM-III-R for which data was informative. In addition, inherited factors plus shared environmental experiences explained 56% of the report of 3 or more symptoms of pathologic gambling and 62% of the diagnosis of pathologic gambling disorder (4 or more symptoms).
Pathogenesis
A number of different neurotransmitters have been thought to be implicated in pathologic gambling. Comings et al. (2001) studied polymorphisms at 31 different genes involved in dopamine, serotonin, norepinephrine, GABA, and other types of metabolism in 139 pathologic gamblers and 139 age, race, and sex-matched controls. Fifteen genes were included in the multivariate regression analysis. The most significant were DRD2 (126450), DRD4 (126452), DAT/DAT1 (SLC6A3; 126455), TPH (191060), ADRA2C (104250), NMDAR1 (138249), and PS1 (104311) genes. Dopamine, serotonin, and norepinephrine genes contributed approximately equally to the risk of pathologic gambling. The results indicated that genes influencing a range of brain functions play an additive role as risk factors for pathologic gambling. Comings et al. (2001) suggested that multigene profiles in specific individuals may help in choosing appropriate treatment.
Tippmann-Peikert et al. (2007) reported 3 patients with restless legs syndrome (RLS; 102300) who developed pathologic gambling after treatment with dopamine agonists. The behavior was dose-dependent, and there were no other compulsive behaviors. Pathologic gambling resolved in all 3 patients after discontinuation of the medication. In 1 patient, treatment with gabapentin led to resolution of RLS symptoms without side effects.
Voon et al. (2007) evaluated 21 patients with Parkinson disease (PD; 168600) who developed pathologic gambling after receiving pharmacologic treatment with dopaminergic agonists. Compared to 42 PD patients without compulsive behaviors, those who developed pathologic gambling had a younger age at PD onset, higher novelty seeking (601696), tended to have medication-induced hypomania or mania, impaired planning, and a personal or family history of alcohol use disorders (see 103780).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
GAMBLING, PATHOLOGIC
|
c0030662
| 7,320 |
omim
|
https://www.omim.org/entry/606349
| 2019-09-22T16:10:29 |
{"doid": ["12399"], "mesh": ["D005715"], "omim": ["606349"], "icd-9": ["312.31"], "icd-10": ["F63.0"]}
|
Human African Trypanosomiasis (HAT), also called sleeping sickness, is a vector-borne parasitic disease caused by a protozoa of the Trypanosoma genus transmitted by the bite of a tsetse fly (genus Glossina), that is found under its chronic form (average duration of 3 years) in western and central Africa (in case of the T. brucei gambiense sub-species), and under its acute form (lasting from few weeks to 6 months) in eastern and southern Africa (in case of the T. brucei rhodesiense sub-species). HAT comprises an initial hemo-lymphatic stage characterized by fever, weakness, musculoskeletal pain, anemia, and lymphadenopathy, along with dermatologic, cardiac and endocrine complications or hepatosplenomegaly, followed by a meningo-encephalitic stage characterized by neurologic involvement (sleep disturbances, psychiatric disorders, seizures) that progresses, in the absence of treatment, towards a fatal meningoencephalitis.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
African trypanosomiasis
|
c0041228
| 7,321 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=3385
| 2021-01-23T18:07:05 |
{"gard": ["7826"], "mesh": ["D014353"], "umls": ["C0041228"], "icd-10": ["B56.0", "B56.1", "B56.9"], "synonyms": ["Sleeping sickness"]}
|
Oculodentodigital dysplasia (ODDD) is characterized by craniofacial, neurologic, limb and ocular abnormalities.
## Epidemiology
To date, approximately 250 cases have been described worldwide (the majority of whom were white individuals).
## Clinical description
The disease is characterized by wide intra- and interfamilial phenotypic variability. The typical craniofacial anomalies include a thin nose with hypoplastic alae nasi, small anteverted nares and a prominent columella, mandibular overgrowth, cleft palate, and microcephaly. Skeletal manifestations consist of syndactyly (involving the 4th and 5th fingers and/or 2nd to 4th toes), camptodactyly, and clinodactyly due to hypoplasia or aplasia of the middle phalanges. Cranial hyperostosis and broad tubular bones may be present. Ophthalmic anomalies include decreased visual acuity, microphthalmia, microcornea, cataracts, glaucoma, iris abnormalities and optic atrophy. Less frequent ocular findings are nystagmus, palpebral fissure hypoplasia, epicanthal folds and convergent strabismus. The majority of patients with ODDD have abnormal primary and permanent dentition with microdontia, partial anodontia, enamel hypoplasia, multiple caries and early tooth loss. Neurologic symptoms are inconsistent but frequent and include dysarthria, neurogenic bladder disturbances, spastic paraparesis, ataxia, anterior tibial muscle weakness, and seizures. Some patients have dysplastic ears and conductive hearing loss. Mild psychomotor delay has been described. Brain magnetic resonance imaging (MRI) may show white matter abnormalities. Brittle nails and hair abnormalities (hypotrichosis and slow growth) may be present. Cardiac anomalies, including arrhythmias or congenital malformations (ventricular septal defect) have been described but are not frequent. Umbilical hernia, congenital optociliary veins, and recurrent ketotic hypoglycemia in early childhood have been reported in a single case.
## Etiology
ODDD is caused by heterozygous mutations in the GJA1 gene (6q22-q23), which encodes the gap junction protein connexin 43 (Cx43). Over 40 causative mutations have been identified. Mutations of the GJA1 gene have also been observed in syndactyly type 3 (see this term), suggesting that both syndromes are part of the same spectrum. In the majority of cases, ODDD is inherited in an autosomal dominant manner with high penetrance and variable expression. Advanced paternal age has been noted in sporadic ODDD cases. Five families with apparently autosomal recessive inheritance have been reported, but this remains to be confirmed.
## Diagnostic methods
Diagnosis is based on clinical findings and can be confirmed by molecular studies.
## Differential diagnosis
Differential diagnosis includes a wide number of syndromes that present with skeletal, ocular, dental and neurological manifestations.
## Antenatal diagnosis
In familial cases, the recurrence risk is elevated and prenatal mutational analysis may be considered.
## Genetic counseling
Genetic counseling should be offered to all ODDD patients.
## Management and treatment
Management is multidisciplinary. Regular follow-up should include a complete eye examination, and neurological, hearing and dental evaluation. As blindness due to glaucoma can occur, patients at risk should receive anti-glaucoma treatment. Plastic or orthopedic surgery is indicated for severe limb malformations. Early recognition of the syndrome is of crucial importance in prevention and treatment of the wide variety of clinical manifestations.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Oculodentodigital dysplasia
|
c0812437
| 7,322 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2710
| 2021-01-23T18:22:15 |
{"gard": ["7239"], "mesh": ["C563160"], "omim": ["164200", "257850"], "umls": ["C0812437"], "icd-10": ["Q87.8"], "synonyms": ["Meyer-Schwickerath syndrome", "ODDD syndrome", "Oculodentoosseous dysplasia"]}
|
A number sign (#) is used with this entry because of evidence that immunodeficiency-61 (IMD61) is caused by hemizygous mutation in the SH3KBP1 gene (300374) on chromosome Xp22. One such family has been reported.
Description
Immunodeficiency-61 (IMD61) is an X-linked recessive primary immunodeficiency characterized by onset of recurrent infections in early childhood due to impaired antibody production. Affected individuals have normal numbers of circulating B and T cells, but B cells have an intrinsic defect in antibody production (summary by Keller et al., 2018).
For a general phenotypic description of X-linked agammaglobulinemia, see 300755.
Clinical Features
Keller et al. (2018) reported 2 brothers with recurrent infections and impaired antibody responses. The proband was a 12-year-old boy with deficiencies of IgM, IgG2, and IgG4 who experienced recurrent bacterial infections until his fourth year of life. He overcame this period of severe early infections and since that time showed no obvious symptoms of a compromised immune system. Detailed study of the patient's B cells showed normal levels of circulating B cells and subtypes, including transitional, naive, memory cells, and plasmablasts, although there were some subtle abnormalities. However, his IgG response to pneumococcal vaccination (polysaccharide) was insufficient, although responses to tetanus toxoid were normal. Detailed studies of patient T cells showed no abnormalities of proliferation, activation, or intracellular signaling. His brother (patient 2) had constant infections since early childhood and died at age 15 years from a bacterial infection complicated by septic shock and multiorgan failure. The brother had decreased serum titers of all antibodies, including total IgG and IgA. In addition, both brothers were diagnosed at age 11 with ADHD, mildly impaired adaptive skills, and obesity.
Inheritance
The transmission pattern of IMD61 in the family reported by Keller et al. (2018) was consistent with X-linked recessive inheritance.
Mapping
In linkage studies, Mensink et al. (1986) found evidence suggesting at least 2 types of X-linked agammaglobulinemia: one located at Xq21.3-q22 (300755) and another unlinked to the marker in this area and possibly located in the Xp22 band.
Molecular Genetics
In 2 brothers with IMD61, Keller et al. (2018) identified a hemizygous 247.5-kb intragenic deletion in the SH3KBP1 gene that deleted exons 2 through 6, which encode 2 SH3 domains of the protein (300374.0001). The deletion, which was found by array CGH, was also present in the unaffected mother. Genes adjacent to SH3KBP1 were not affected. Whole-exome sequencing excluded mutations in 395 genes linked with primary immunodeficiencies in humans. In vitro functional expression studies of patient B cells showed a specific defect in the canonical activation of NFKB (see 164011) in response to stimulation of the B-cell receptor (BCR). In contrast, ligation of TLR9 (605474) or CD40 (109535) and treatment of the cells with PMA activated NFKB properly. Other signaling pathways, including Ras (see 190020)-MAPK (see 176872), PI3 kinase (see 171833), and Akt (164730)-mTOR (601231) were unaffected. BCR-induced surface expression of the activation marker CD86 (601020) was decreased in patient cells. Keller et al. (2018) concluded that the deletion caused an intrinsic defect in B cells that impaired central BCR activation pathways and the generation of antibodies.
Animal Model
Kometani et al. (2011) found that specific deletion of the Cin85 gene in murine B cells resulted in impaired T cell-independent antibody responses in vivo and diminished IKKB (603258) and NFKB activation and cellular responses to B cell receptor (BCR) crosslinking in vitro. The findings indicated that Cin85 plays an important role in BCR-mediated survival and proliferation by participating in important signaling pathways.
INHERITANCE \- X-linked recessive GROWTH Weight \- Obesity HEAD & NECK Ears \- Otitis media, recurrent RESPIRATORY \- Respiratory infections, recurrent Nasopharynx \- Sinusitis, recurrent NEUROLOGIC Central Nervous System \- Impaired adaptive skills, mild Behavioral Psychiatric Manifestations \- Attention deficit-hyperactivity disorder IMMUNOLOGY \- Recurrent infections \- Decreased antibodies \- Defective B cell response to stimulation at the B-cell receptor \- Normal levels of circulating B cells \- Normal T cell levels and function MISCELLANEOUS \- Onset in early childhood \- Variable severity \- Two brothers have been reported (last curated April 2019) MOLECULAR BASIS \- Caused by mutation in the SH3-domain kinase-binding protein 1 gene (SH3KBP1, 300374.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
IMMUNODEFICIENCY 61
|
c0221026
| 7,323 |
omim
|
https://www.omim.org/entry/300310
| 2019-09-22T16:20:31 |
{"mesh": ["C537409"], "omim": ["300310"], "orphanet": ["47", "229717"], "synonyms": ["Alternative titles", "AGAMMAGLOBULINEMIA, X-LINKED, TYPE 2", "XLA2"]}
|
Small intestine cancer
Other namesSmall bowel cancer, cancer of the small bowel
Picture of a carcinoid tumour that encroaches into lumen of the small bowel. Pathology specimen. The prominent folds are plicae circulares, a characteristic of small bowel.
SpecialtyGastroenterology, general surgery, oncology
Symptomsvomiting blood, blood in the stool
Small intestine cancer is a cancer of the small intestine. It is relatively rare compared to other gastrointestinal malignancies such as gastric cancer (stomach cancer) and colorectal cancer.[citation needed]
Small intestine cancer can be subdivided into duodenal cancer (the first part of the small intestine) and cancer of the jejunum and ileum (the later two parts of the small intestine). Duodenal cancer has more in common with stomach cancer, while cancer of the jejunum and ileum have more in common with colorectal cancer. Five-year survival rates are 65%.[1]
## Contents
* 1 Histopathologic types
* 2 Risk factors
* 3 Additional images
* 4 References
* 5 External links
## Histopathologic types[edit]
Relative incidence of histopathologic types of small intestine cancers, and their prognoses.[2]
Several different subtypes of small intestine cancer exist. These include:
* Adenocarcinoma
* Gastrointestinal stromal tumor
* Lymphoma
* Carcinoid tumors of the midgut
* Adenocarcinoma
* Carcinoid
## Risk factors[edit]
Endoscopic image of adenocarcinoma of duodenum seen in the post-bulbar duodenum.
Risk factors for small intestine cancer include:[3][4]
* Crohn's disease
* Celiac disease
* Radiation exposure
* Hereditary gastrointestinal cancer syndromes: familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, Peutz–Jeghers syndrome
* Males are 25% more likely to develop the disease
Benign tumours and conditions that may be mistaken for cancer of the small bowel:
* Hamartoma
* Tuberculosis
## Additional images[edit]
* Micrograph of a small intestine neuroendocrine tumour. H&E stain.
## References[edit]
1. ^ "SEER Stat Fact Sheets: Small Intestine Cancer". NCI. Retrieved 18 June 2014.
2. ^ Qubaiah, O.; Devesa, S. S.; Platz, C. E.; Huycke, M. M.; Dores, G. M. (2010). "Small Intestinal Cancer: a Population-Based Study of Incidence and Survival Patterns in the United States, 1992 to 2006". Cancer Epidemiology, Biomarkers & Prevention. 19 (8): 1908–1918. doi:10.1158/1055-9965.EPI-10-0328. ISSN 1055-9965. PMC 2919612. PMID 20647399.
3. ^ Delaunoit T, Neczyporenko F, Limburg PJ, Erlichman C (March 2005). "Pathogenesis and risk factors of small bowel adenocarcinoma: a colorectal cancer sibling?". Am. J. Gastroenterol. 100 (3): 703–10. PMID 15743371.
4. ^ Chen AC, Neugut AI. Malignant Neoplasms of the Small Intestine. eMedicine.com. URL: http://www.emedicine.com/MED/topic2651.htm. Accessed on: June 2, 2006.
## External links[edit]
Classification
D
* ICD-10: C17
* ICD-9-CM: 152
* MeSH: D007414
* v
* t
* e
Digestive system neoplasia
GI tract
Upper
Esophagus
* Squamous cell carcinoma
* Adenocarcinoma
Stomach
* Gastric carcinoma
* Signet ring cell carcinoma
* Gastric lymphoma
* MALT lymphoma
* Linitis plastica
Lower
Small intestine
* Duodenal cancer
* Adenocarcinoma
Appendix
* Carcinoid
* Pseudomyxoma peritonei
Colon/rectum
* Colorectal polyp: adenoma, hyperplastic, juvenile, sessile serrated adenoma, traditional serrated adenoma, Peutz–Jeghers
Cronkhite–Canada
* Polyposis syndromes: Juvenile
* MUTYH-associated
* Familial adenomatous/Gardner's
* Polymerase proofreading-associated
* Serrated polyposis
* Neoplasm: Adenocarcinoma
* Familial adenomatous polyposis
* Hereditary nonpolyposis colorectal cancer
Anus
* Squamous cell carcinoma
Upper and/or lower
* Gastrointestinal stromal tumor
* Krukenberg tumor (metastatic)
Accessory
Liver
* malignant: Hepatocellular carcinoma
* Fibrolamellar
* Hepatoblastoma
* benign: Hepatocellular adenoma
* Cavernous hemangioma
* hyperplasia: Focal nodular hyperplasia
* Nodular regenerative hyperplasia
Biliary tract
* bile duct: Cholangiocarcinoma
* Klatskin tumor
* gallbladder: Gallbladder cancer
Pancreas
* exocrine pancreas: Adenocarcinoma
* Pancreatic ductal carcinoma
* cystic neoplasms: Serous microcystic adenoma
* Intraductal papillary mucinous neoplasm
* Mucinous cystic neoplasm
* Solid pseudopapillary neoplasm
* Pancreatoblastoma
Peritoneum
* Primary peritoneal carcinoma
* Peritoneal mesothelioma
* Desmoplastic small round cell tumor
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Small intestine cancer
|
c0153425
| 7,324 |
wikipedia
|
https://en.wikipedia.org/wiki/Small_intestine_cancer
| 2021-01-18T18:49:57 |
{"gard": ["9385"], "umls": ["C0153425"], "wikidata": ["Q1271826"]}
|
Omasitis is an inflammation of the omasum,[1] the third compartment of the stomach in ruminants. It usually accompanies rumenitis, and is often caused by infection with Fusobacterium necrophorum.
## References[edit]
1. ^ Douglas, M. Anderson, M.A.; D. Novak, PhD, Patricia; Jefferson, Keith, M.A. (2011). Dorland's Illustrated Medical Dictionary. 1 (32 ed.). Elsevier. p. 1319. ISBN 978-1416062578.
This veterinary medicine–related article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Omasitis
|
c0267228
| 7,325 |
wikipedia
|
https://en.wikipedia.org/wiki/Omasitis
| 2021-01-18T18:36:57 |
{"wikidata": ["Q18357097"]}
|
Quebec platelet syndrome (QPS) is a platelet granule disorder characterized by moderate to severe bleeding after trauma, surgery or obstetric interventions, frequent ecchymoses, mucocutaneous bleeding and muscle and joint bleeds.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Quebec platelet disorder
|
c1866423
| 7,326 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=220436
| 2021-01-23T19:05:02 |
{"gard": ["8345"], "mesh": ["C536260"], "omim": ["601709"], "umls": ["C1866423"], "icd-10": ["D69.1"], "synonyms": ["Factor V Quebec"]}
|
A number sign (#) is used with this entry because of evidence that this form of congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A9; MDDGA9) is caused by homozygous mutation in the DAG1 gene (128239) on chromosome 3p21.
Mutation in the DAG1 gene can also cause the less severe disorder limb-girdle muscular dystrophy-dystroglycanopathy (type C9, MDDGC9; 613818).
Description
Congenital muscular dystrophy-dystroglycanopathy with brain and eye anomalies (type A) is an autosomal recessive disorder with characteristic brain and eye malformations, profound mental retardation, and congenital muscular dystrophy. The phenotype includes the alternative clinical designation Walker-Warburg syndrome (WWS), which is associated with death in infancy. The disorder represents the most severe end of a phenotypic spectrum of similar disorders resulting from defective glycosylation of alpha-dystroglycan (DAG1), collectively known as 'dystroglycanopathies' (summary by Geis et al., 2013 and Riemersma et al., 2015).
For a general phenotypic description and a discussion of genetic heterogeneity of muscular dystrophy-dystroglycanopathy type A, see MDDGA1 (236670).
Clinical Features
Geis et al. (2013) reported sisters, born of presumably unrelated Libyan parents, with apparent onset of severe developmental delay and hypotonia at age 4 months. Examination at ages 2 years 8 months and 3 years 7 months, respectively, showed severe mental retardation and muscular hypotonia without any ability to sit or walk. While there was a lack of head control in the younger girl, the other sib had gained some limited ability to balance the head. Neither girl was able to speak. Ophthalmic examinations revealed several abnormalities, including cataract, retinal dystrophy, severe myopia, and buphthalmos. Serum creatine kinase was increased, and muscle biopsy showed a dystrophic myopathy with moderate fiber size variability and absence of immunostaining for alpha-dystroglycan. Brain imaging performed in 1 of the patients showed multiple abnormalities consistent with muscle-eye-brain disease: there was flattening and kinking of the pons and brainstem, hypoplastic cerebellar vermis, subcortical cysts in the cerebellar hemispheres, polymicrogyria with frontal agyria, ventricular dilatation, and thinning of the corpus callosum. In addition, there were severe white matter abnormalities with T2-weighted hyperintensities and multiple large cystic lesions in a somewhat radial orientation from the frontal to parietal subcortical regions and well as smaller subcortical cysts in an anterior-temporal distribution.
Riemersma et al. (2015) reported a consanguineous Israeli-Arab family in which 5 female infants were born with multiple severe abnormalities consistent with WWS and died within a few hours to 3.5 months of life. Features included hydrocephalus, eye anomalies such as microphthalmia, buphthalmos, corneal opacities, and glaucoma, hypotonia with absent reflexes and lack of spontaneous movements, and respiratory failure. One patient had holoprosencephaly. Two patients had increased serum creatine kinase, and muscle biopsy of 1 patient showed marked variation in fiber size. Brain imaging in 3 patients showed scattered intracranial calcifications, but intrauterine infections were excluded.
Inheritance
The transmission pattern of MDDGA9 in the families reported by Geis et al. (2013) and Riemersma et al. (2015) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 2 sisters, born of presumably unrelated Libyan parents, with MDDGA9, Geis et al. (2013) identified a homozygous missense mutation in the DAG1 gene (C669F; 128239.0004). The mutation was found by whole-exome sequencing and confirmed by direct sequencing. The unaffected mother was heterozygous for the mutation. The cys669 residue, postulated to form a covalent disulfide bond with cys713 within beta-dystroglycan, is important for the structure of beta-dystroglycan and thus most likely also for the function of the alpha- and beta-dystroglycan complex. Functional studies of the variant were not performed.
In 5 female infants from a consanguineous Israeli-Arab family with MDDGA9 resulting in death soon after birth, Riemersma et al. (2015) identified a homozygous truncating mutation in the DAG1 gene (128239.0005). The mutation was found by a combination of homozygosity mapping and whole-exome sequencing. Patient fibroblasts that were transformed to myoblasts showed no detectable properly glycosylated alpha-dystroglycan and no detectable alpha- or beta-dystroglycan protein, consistent with complete absence of both protein isoforms.
Animal Model
Moore et al. (2002) showed that brain-selective deletion of dystroglycan in mice is sufficient to cause congenital muscular dystrophy-like brain malformations, including disarray of cerebral cortical layering, fusion of cerebral hemispheres and cerebellar folia, and aberrant migration of granule cells. Dystroglycan-null brain loses its high affinity binding to the extracellular matrix protein laminin (see 150240) and shows discontinuities in the pial surface basal lamina (glia limitans) that probably underlie the neuronal migration errors. Furthermore, mutant mice have severely blunted hippocampal long-term potentiation with electrophysiologic characterization, indicating that dystroglycan might have a postsynaptic role in learning and memory. Moore et al. (2002) concluded that these data strongly supported the hypothesis that defects in dystroglycan are central to the pathogenesis of structural and functional brain abnormalities seen in congenital muscular dystrophies.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Macrocephaly Eyes \- Microphthalmia \- Buphthalmos \- Retinal dystrophy \- Cataract \- Myopia \- Glaucoma RESPIRATORY \- Respiratory failure MUSCLE, SOFT TISSUES \- Hypotonia \- Muscular dystrophy \- Absence of immunostaining for alpha-dystroglycan (family A) \- Absence of immunostaining for alpha- and beta-dystroglycan (family B) NEUROLOGIC Central Nervous System \- Delayed psychomotor development, severe \- Lack of speech \- Poor head control \- Hydrocephalus (family B) \- Thin cortical layer \- Polymicrogyria \- Frontal agyria \- Neuronal migration defects \- Dilated ventricles \- Thin corpus callosum \- Kinking of the pons and brainstem \- Hypoplastic cerebellar vermis \- Cerebellar cysts (family A) \- White matter abnormalities (family A) \- Leukodystrophy (family A) \- Cystic lesions (family A) \- Intracranial calcifications (family B) LABORATORY ABNORMALITIES \- Increased serum creatine kinase MISCELLANEOUS \- Onset in infancy \- Variable severity \- Death in first days of life (family B) \- Two unrelated families have been reported (last curated August 2015) MOLECULAR BASIS \- Caused by mutation in the dystrophin-associated glycoprotein-1 gene (DAG1, 128239.0004 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (CONGENITAL WITH BRAIN AND EYE ANOMALIES), TYPE A, 9
|
c0265221
| 7,327 |
omim
|
https://www.omim.org/entry/616538
| 2019-09-22T15:48:36 |
{"doid": ["0111232"], "mesh": ["D058494"], "omim": ["616538"], "orphanet": ["370997", "899"], "synonyms": ["Alternative titles", "WALKER-WARBURG SYNDROME OR MUSCLE-EYE BRAIN DISEASE, DAG1-RELATED", "MEB disease with bilateral multicystic leucodystrophy"]}
|
Bilateral striopallidodentate calcinosis (BSPDC, also erroneously called Fahr disease) is characterized by the accumulation of calcium deposits in different brain regions, particularly the basal ganglia and dentate nucleus, and is often associated with neurodegeneration.
## Epidemiology
The prevalence of BSPDC is not known, however it is very rare and fewer than 200 cases have been reported. BSPDC is more common in men (male:female ratio 2:1).
## Clinical description
BSPCD can be asymptomatic. Symptomatic forms usually manifest in the fourth decade of life, whereas calcification may be found in the second decade. Patients present with progressive movement disorders, including parkinsonism, chorea, tremor, dystonia, athetosis and orofacial dyskinesia, ataxia and neuropsychiatric disorders including difficultly with concentration and memory, personality and/or behavior changes, and dementia. The first manifestations often include clumsiness, fatigability, unsteady gait, slow or slurred speech, dysphagia, involuntary movements or muscle cramping. Seizures occur frequently. Urinary incontinence may occur.
## Etiology
The causative gene or genes are not known. Linkage to chromosome 14q has been established in one family. Calcium is the major element deposited on the basal ganglia and accounts for the radiologic appearance of the disease. It is thought that the calcifications observed are a marker of the disease rather than a cause of the clinical symptoms.
## Diagnostic methods
Single proton emission computed tomography (SPECT) reveals markedly decreased perfusion to the basal ganglia bilaterally with decreased perfusion to the cerebral cortices. Diagnosis is based on CT or MRI evidence of bilateral, almost symmetric, calcifications of one or more of the following areas: basal ganglia, dentate nuclei, thalamus and cerebral white matter. Diagnosis is further based on normal childhood growth and development and the absence of parathyroid or other known neurologic disorders. Electroencephalogram, nerve conduction studies, and pattern shift visual-evoked potentials studies are usually normal and brainstem auditory-evoked potentials may vary from normal to minor abnormalities.
## Differential diagnosis
Differential diagnoses include hypoparathyroidism and pseudohypoparathyroidism, which can usually be excluded by normal serum levels of parathyroid hormone, Kenny-Caffey syndrome type 1, neurodegeneration with iron accumulation, Cockayne syndrome and Aicardi-Goutières syndrome (see these terms).
## Antenatal diagnosis
Genetic counseling may be offered.However, there is currently no possibility of antenatal diagnosis.
## Genetic counseling
It can be familial or sporadic. Over 30 families with the familial form have been reported. The familial form of idiopathic basal ganglia calcification is inherited in an autosomal dominant manner.
## Management and treatment
There is no specific treatment available. Treatment based on amelioration of manifestations, including pharmacologic treatment for anxiety, depression, obsessive-compulsive behaviors and dystonia, may be attempted.
## Prognosis
Prognosis is not fully understood due to a lack of longitudinal studies. However, while asymptomatic cases have been observed in individuals younger than 25 years old, it is possible that symptoms may appear with increasing age.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Bilateral striopallidodentate calcinosis
|
c0393590
| 7,328 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1980
| 2021-01-23T18:53:26 |
{"gard": ["6406"], "omim": ["213600", "615007", "615483", "616413", "618824"], "umls": ["C0393590"], "icd-10": ["G23.8"], "synonyms": ["BSPDC", "Cerebrovascular ferrocalcinosis", "Idiopathic basal ganglia calcification", "PFBC", "Primary familial brain calcification"]}
|
The newly described 8q12 microduplication syndrome is associated with unusual and characteristic multi-organ clinical features, which include hearing loss, congenital heart defects, intellectual disability, hypotonia in infancy, and Duane anomaly (see this term).
## Epidemiology
It has been described in two patients.
## Clinical description
The mild facial dysmorphism is characterized by high, arched eyebrows and unilateral narrowing of the palpebral fissure and retraction of the globe caused by Duane anomaly (Duane anomaly is a form of complex strabismus characterized by limited ocular abduction and variably limited adduction accompanied by retraction of the globe, which narrows the palpebral fissure).
## Etiology
This microduplication was identified by microarray-based comparative genomic hybridization (aCGH). The lack of recurrent breakpoints in these two cases and the absence of any low-copy repeats (LCR) pairs that flank these de novo events do not support non-allelic homologous recombination as the mutation mechanism. The 8q12 region includes CHD7 and it is proposed that this gene, associated with CHARGE syndrome by haploinsufficiency, causes a different phenotype by gain-of-dosage.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
8q12 microduplication syndrome
|
c4304504
| 7,329 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=228399
| 2021-01-23T19:06:33 |
{"gard": ["12816"], "icd-10": ["Q92.3"], "synonyms": ["Dup(8)(q12)", "Trisomy 8q12"]}
|
Uterine perforation
SpecialtyEmergency medicine
Uterine perforation is a potential complication of any intrauterine procedure. It may be associated with injury to surrounding blood vessels or viscera such as the bladder or intestine. If not diagnosed at the time of the procedure it can occasionally result in massive hemorrhage or sepsis; however, the majority of uterine perforations are sub-clinical and safely resolve by themselves without treatment and do not cause any significant long-term damage.[1][2][3][4][5] Risk factors include cervical stenosis during trans-cervical procedures or decreased strength of the myometrial wall as in pregnancy or menopause.[6]
## See also[edit]
* Uterine rupture
## References[edit]
1. ^ ""You need not worry about long-term effects either. A uterine perforation presents no risk of uterine rupture during pregnancy or any other threat to your health. "Typically, a perforation heals up and you never know it was there," added Dr. Sholes-Douglas."". Archived from the original on 2015-05-02. Retrieved 2015-06-30.
2. ^ ""Most perforations ... tend to be located in the fundus and are usually self-limiting and less serious"". Archived from the original on 2015-07-06. Retrieved 2015-07-05.
3. ^ "Uterine perforations ... are rarely noticed and almost never dangerous.... Since none of these resulted in complications, ... the authors recommended no treatment for the majority of known or suspected uterine perforations."
4. ^ "When this happens, as long as no internal organs (intestines, bladder, or rectum) or large blood vessels are damaged, the hole will almost always heal itself without further surgery."
5. ^ "In most cases of perforation there are no long term consequences."
6. ^ utdol.com > Uterine perforation during gynecologic procedures Author: Barbara S Levy, MD, PS. Retrieved on Feb 14, 2010
## External links[edit]
Classification
D
* ICD-10: S37
* ICD-9-CM: 867.4-867.5
* MeSH: D014595
* v
* t
* e
Nonmusculoskeletal injuries of abdomen and pelvis
Abdomen / GI
* Ruptured spleen
* Blunt splenic trauma
* Traumatic diaphragmatic hernia
* Gastrointestinal perforation
* Liver injury
* Pancreatic injury
Pelvic
* Uterine perforation
* Penile fracture
This surgery article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Uterine perforation
|
c0042139
| 7,330 |
wikipedia
|
https://en.wikipedia.org/wiki/Uterine_perforation
| 2021-01-18T18:56:13 |
{"mesh": ["D014595"], "icd-9": ["867.4", "867.5"], "icd-10": ["S37"], "wikidata": ["Q3918693"]}
|
Inclusion body myopathy 2 is a condition that primarily affects skeletal muscles, which are muscles that the body uses for movement. This disorder causes muscle weakness that appears in late adolescence or early adulthood and worsens over time.
The first sign of inclusion body myopathy 2 is weakness of a muscle in the lower leg called the tibialis anterior. This muscle helps control up-and-down movement of the foot. Weakness in the tibialis anterior alters the way a person walks and makes it difficult to run and climb stairs. As the disorder progresses, weakness also develops in muscles of the upper legs, hips, shoulders, and hands. Unlike most forms of myopathy, inclusion body myopathy 2 usually does not affect the quadriceps, which are a group of large muscles at the front of the thigh. This condition also does not affect muscles of the eye or heart, and it does not cause neurological problems. Weakness in leg muscles makes walking increasingly difficult, and most people with inclusion body myopathy 2 require wheelchair assistance within 20 years after signs and symptoms appear.
People with the characteristic features of inclusion body myopathy 2 have been described in several different populations. When the condition was first reported in Japanese families, researchers called it distal myopathy with rimmed vacuoles (DMRV) or Nonaka myopathy. When a similar disorder was discovered in Iranian Jewish families, researchers called it rimmed vacuole myopathy or hereditary inclusion body myopathy (HIBM). It has since become clear that these conditions are variations of a single disorder caused by mutations in the same gene.
## Frequency
More than 200 people with inclusion body myopathy 2 have been reported. Most are of Iranian Jewish descent; the condition affects an estimated 1 in 1,500 people in this population. Additionally, at least 15 people in the Japanese population have been diagnosed with this disorder. Inclusion body myopathy 2 has also been found in several other ethnic groups worldwide.
## Causes
Mutations in the GNE gene cause inclusion body myopathy 2. The GNE gene provides instructions for making an enzyme found in cells and tissues throughout the body. This enzyme is involved in a chemical pathway that produces sialic acid, which is a simple sugar that attaches to the ends of more complex molecules on the surface of cells. By modifying these molecules, sialic acid influences a wide variety of cellular functions including cell movement (migration), attaching cells to one another (adhesion), signaling between cells, and inflammation.
The mutations responsible for inclusion body myopathy 2 reduce the activity of the enzyme produced from the GNE gene, which decreases the production of sialic acid. As a result, less of this simple sugar is available to attach to cell surface molecules. Researchers are working to determine how a shortage of sialic acid leads to progressive muscle weakness in people with inclusion body myopathy 2. Sialic acid is important for the normal function of many different cells and tissues, so it is unclear why the signs and symptoms of this disorder appear to be limited to the skeletal muscles.
### Learn more about the gene associated with Inclusion body myopathy 2
* GNE
## Inheritance Pattern
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Inclusion body myopathy 2
|
c1853926
| 7,331 |
medlineplus
|
https://medlineplus.gov/genetics/condition/inclusion-body-myopathy-2/
| 2021-01-27T08:25:31 |
{"gard": ["9493"], "mesh": ["C536816"], "omim": ["605820"], "synonyms": []}
|
X-linked recessive disorder characterised by impulsive behaviour
Brunner syndrome
Other namesMonoamine oxidase A deficiency
This condition is inherited in an X-linked recessive manner.
Brunner syndrome is a rare genetic disorder associated with a mutation in the MAOA gene. It is characterized by lower than average IQ (typically about 85), problematic impulsive behavior (such as pyromania, hypersexuality and violence), sleep disorders and mood swings.[1][2] It was identified in fourteen males from one family in 1993.[1][3] It has since been discovered in additional families.[4]
## Contents
* 1 Causes
* 2 Diagnosis
* 3 Treatment
* 4 History
* 5 Society and culture
* 6 References
* 7 External links
## Causes[edit]
Brunner syndrome is caused by a monoamine oxidase A (MAOA) deficiency, which leads to an excess of monoamines in the brain, such as serotonin, dopamine, and norepinephrine (noradrenaline). In both mice and humans, a mutation was located on the eighth exon of the MAO-A gene, which created a dysfunctional MAO-A gene.[5][6] The regular function of MAO-A, breaking down monoamines, is disrupted, and monoamines build up within the brain. Mice that lacked a functional MAO-A gene displayed higher levels of aggression, in comparison to mice with a functional MAO-A gene.[6]
## Diagnosis[edit]
Upon suspicion of Brunner syndrome and after having eliminated other potential suspects via means of differential diagnosis, Brunner syndrome is diagnosed by genetic testing for specific mutations of the MAOA gene. Since the syndrome is so rare, it's usually only suspected and tested for if there are other diagnosed instances of the syndrome in one's direct family.[citation needed]
## Treatment[edit]
Progesterone & Rauwolfia serpentina (containing Reserpine) are a possible treatment as they both increase MAO-A activity.[citation needed]
## History[edit]
Brunner Syndrome was described in 1993 by H.G. Brunner and his colleagues upon the discovery of a particular genetic defect in male members of a large Dutch family.[5] Brunner found that all of the male family members with this defect reacted aggressively when angry, fearful, or frustrated. The defect discovered was later found to be a mutation in the gene that codes for monoamine oxidase A (MAOA gene).[5] Brunner said that an "MAO-A deficiency is associated with a recognizable behavioural phenotype that included disturbed regulation of impulsive aggression".[5]
A letter published by Hebebrand and Klug (1995)[7] criticized Brunner's findings for not using strict DSM criteria.
## Society and culture[edit]
Brunner's findings have been used to argue that genetics, rather than decision-making processes, can cause criminal activity.[8] Evidence supporting the genetic defense stems from both Brunner's findings and a series of studies on mice.[9] To prove the correlation between MAO-A deficiency and aggression in courts, it is often contended that individuals cannot be held accountable for their genes, and as a result, should not be held responsible for their dispositions and resulting actions.[8][9]
## References[edit]
1. ^ a b Hunter P (September 2010). "The psycho gene". EMBO Rep. 11 (9): 667–9. doi:10.1038/embor.2010.122. PMC 2933872. PMID 20805840.
2. ^ Online Mendelian Inheritance in Man (OMIM): 300615
3. ^ Brunner HG; Nelen MR; van Zandvoort P; Abeling NGGM; van Gennip AH; Wolters EC; Kuiper MA; Ropers HH; van Oost BA (June 1993). "X-linked borderline mental retardation with prominent behavioral disturbance: phenotype, genetic localization, and evidence for disturbed monoamine metabolism". Am. J. Hum. Genet. 52 (6): 1032–9. PMC 1682278. PMID 8503438.
4. ^ Piton A, Redin C, Mandel JL (August 2013). "XLID-causing mutations and associated genes challenged in light of data from large-scale human exome sequencing". Am. J. Hum. Genet. 93 (2): 368–83. doi:10.1016/j.ajhg.2013.06.013. PMC 3738825. PMID 23871722.
5. ^ a b c d Brunner HG, Nelen M, Breakefield XO, Ropers HH, van Oost BA (October 1993). "Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A". Science. 262 (5133): 578–80. Bibcode:1993Sci...262..578B. doi:10.1126/science.8211186. PMID 8211186.
6. ^ a b Scott, AL; Bortolato, M; Chen, K; Shih, JC (2008-05-07). "Novel monoamine oxidase A knock out mice with human-like spontaneous mutation". NeuroReport. 19 (7): 739–43. doi:10.1097/WNR.0b013e3282fd6e88. PMC 3435113. PMID 18418249.
7. ^ Hebebrand J, Klug B (September 1995). "Specification of the phenotype required for men with monoamine oxidase type A deficiency". Hum. Genet. 96 (3): 372–6. doi:10.1007/BF00210430. PMID 7649563.
8. ^ a b Halwani S, Krupp DB (2004). "The genetic defence: the impact of genetics on the concept of criminal responsibility". Health Law J. 12: 35–70. PMID 16539076.
9. ^ a b Baker LA, Bezdjian S, Raine A (2006). "Behavioral genetics: the science of antisocial behavior". Law Contemp Probl. 69 (1–2): 7–46. PMC 2174903. PMID 18176636.
## External links[edit]
Classification
D
* ICD-10: E70.8
* OMIM: 300615
* MeSH: C563156 C563156, C563156
* DiseasesDB: 32391
External resources
* Orphanet: 3057
* v
* t
* e
X-linked disorders
X-linked recessive
Immune
* Chronic granulomatous disease (CYBB)
* Wiskott–Aldrich syndrome
* X-linked severe combined immunodeficiency
* X-linked agammaglobulinemia
* Hyper-IgM syndrome type 1
* IPEX
* X-linked lymphoproliferative disease
* Properdin deficiency
Hematologic
* Haemophilia A
* Haemophilia B
* X-linked sideroblastic anemia
Endocrine
* Androgen insensitivity syndrome/Spinal and bulbar muscular atrophy
* KAL1 Kallmann syndrome
* X-linked adrenal hypoplasia congenita
Metabolic
* Amino acid: Ornithine transcarbamylase deficiency
* Oculocerebrorenal syndrome
* Dyslipidemia: Adrenoleukodystrophy
* Carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency
* Pyruvate dehydrogenase deficiency
* Danon disease/glycogen storage disease Type IIb
* Lipid storage disorder: Fabry's disease
* Mucopolysaccharidosis: Hunter syndrome
* Purine–pyrimidine metabolism: Lesch–Nyhan syndrome
* Mineral: Menkes disease/Occipital horn syndrome
Nervous system
* X-linked intellectual disability: Coffin–Lowry syndrome
* MASA syndrome
* Alpha-thalassemia mental retardation syndrome
* Siderius X-linked mental retardation syndrome
* Eye disorders: Color blindness (red and green, but not blue)
* Ocular albinism (1)
* Norrie disease
* Choroideremia
* Other: Charcot–Marie–Tooth disease (CMTX2-3)
* Pelizaeus–Merzbacher disease
* SMAX2
Skin and related tissue
* Dyskeratosis congenita
* Hypohidrotic ectodermal dysplasia (EDA)
* X-linked ichthyosis
* X-linked endothelial corneal dystrophy
Neuromuscular
* Becker's muscular dystrophy/Duchenne
* Centronuclear myopathy (MTM1)
* Conradi–Hünermann syndrome
* Emery–Dreifuss muscular dystrophy 1
Urologic
* Alport syndrome
* Dent's disease
* X-linked nephrogenic diabetes insipidus
Bone/tooth
* AMELX Amelogenesis imperfecta
No primary system
* Barth syndrome
* McLeod syndrome
* Smith–Fineman–Myers syndrome
* Simpson–Golabi–Behmel syndrome
* Mohr–Tranebjærg syndrome
* Nasodigitoacoustic syndrome
X-linked dominant
* X-linked hypophosphatemia
* Focal dermal hypoplasia
* Fragile X syndrome
* Aicardi syndrome
* Incontinentia pigmenti
* Rett syndrome
* CHILD syndrome
* Lujan–Fryns syndrome
* Orofaciodigital syndrome 1
* Craniofrontonasal dysplasia
* v
* t
* e
Inborn error of amino acid metabolism
K→acetyl-CoA
Lysine/straight chain
* Glutaric acidemia type 1
* type 2
* Hyperlysinemia
* Pipecolic acidemia
* Saccharopinuria
Leucine
* 3-hydroxy-3-methylglutaryl-CoA lyase deficiency
* 3-Methylcrotonyl-CoA carboxylase deficiency
* 3-Methylglutaconic aciduria 1
* Isovaleric acidemia
* Maple syrup urine disease
Tryptophan
* Hypertryptophanemia
G
G→pyruvate→citrate
Glycine
* D-Glyceric acidemia
* Glutathione synthetase deficiency
* Sarcosinemia
* Glycine→Creatine: GAMT deficiency
* Glycine encephalopathy
G→glutamate→
α-ketoglutarate
Histidine
* Carnosinemia
* Histidinemia
* Urocanic aciduria
Proline
* Hyperprolinemia
* Prolidase deficiency
Glutamate/glutamine
* SSADHD
G→propionyl-CoA→
succinyl-CoA
Valine
* Hypervalinemia
* Isobutyryl-CoA dehydrogenase deficiency
* Maple syrup urine disease
Isoleucine
* 2-Methylbutyryl-CoA dehydrogenase deficiency
* Beta-ketothiolase deficiency
* Maple syrup urine disease
Methionine
* Cystathioninuria
* Homocystinuria
* Hypermethioninemia
General BC/OA
* Methylmalonic acidemia
* Methylmalonyl-CoA mutase deficiency
* Propionic acidemia
G→fumarate
Phenylalanine/tyrosine
Phenylketonuria
* 6-Pyruvoyltetrahydropterin synthase deficiency
* Tetrahydrobiopterin deficiency
Tyrosinemia
* Alkaptonuria/Ochronosis
* Tyrosinemia type I
* Tyrosinemia type II
* Tyrosinemia type III/Hawkinsinuria
Tyrosine→Melanin
* Albinism: Ocular albinism (1)
* Oculocutaneous albinism (Hermansky–Pudlak syndrome)
* Waardenburg syndrome
Tyrosine→Norepinephrine
* Dopamine beta hydroxylase deficiency
* reverse: Brunner syndrome
G→oxaloacetate
Urea cycle/Hyperammonemia
(arginine
* aspartate)
* Argininemia
* Argininosuccinic aciduria
* Carbamoyl phosphate synthetase I deficiency
* Citrullinemia
* N-Acetylglutamate synthase deficiency
* Ornithine transcarbamylase deficiency/translocase deficiency
Transport/
IE of RTT
* Solute carrier family: Cystinuria
* Hartnup disease
* Iminoglycinuria
* Lysinuric protein intolerance
* Fanconi syndrome: Oculocerebrorenal syndrome
* Cystinosis
Other
* 2-Hydroxyglutaric aciduria
* Aminoacylase 1 deficiency
* Ethylmalonic encephalopathy
* Fumarase deficiency
* Trimethylaminuria
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Brunner syndrome
|
c0796275
| 7,332 |
wikipedia
|
https://en.wikipedia.org/wiki/Brunner_syndrome
| 2021-01-18T18:44:03 |
{"gard": ["3531"], "mesh": ["C563156"], "umls": ["C0796275"], "orphanet": ["3057"], "wikidata": ["Q4979092"]}
|
Osteomesopyknosis is a bone disorder characterized by abnormal hardening of bone (osteosclerosis). It is generally limited to the axial spine, pelvis, and proximal part of the long bones, which is what distinguishes this condition from other sclerosing bone disorders. It is usually diagnosed incidentally in young adults complaining of back pain. Osteomesopyknosis is inherited in an autosomal dominant manner but the genetic cause has not yet been identified. It is generally benign and life expectancy is normal.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Osteomesopyknosis
|
c0432264
| 7,333 |
gard
|
https://rarediseases.info.nih.gov/diseases/391/osteomesopyknosis
| 2021-01-18T17:58:32 |
{"mesh": ["C537792"], "omim": ["166450"], "umls": ["C0432264"], "orphanet": ["2777"], "synonyms": ["Axial osteosclerosis"]}
|
Leprosy, also called Hansen disease, is a disorder known since ancient times. It is caused by bacteria called Mycobacterium leprae and is contagious, which means that it can be passed from person to person. It is usually contracted by breathing airborne droplets from affected individuals' coughs and sneezes, or by coming into contact with their nasal fluids. However, it is not highly transmissible, and approximately 95 percent of individuals who are exposed to Mycobacterium leprae never develop leprosy. The infection can be contracted at any age, and signs and symptoms can take anywhere from several months to 20 years to appear.
Leprosy affects the skin and the peripheral nerves, which connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, and heat. Most affected individuals have areas of skin damage (cutaneous lesions) and problems with nerve function (peripheral neuropathy); however, the severity and extent of the problems vary widely. Leprosy occurs on a spectrum, in which the most severe form is called multibacillary or lepromatous, and the least severe form is called paucibacillary or tuberculoid. Patterns of signs and symptoms intermediate between these forms are sometimes called borderline forms.
Multibacillary leprosy usually involves a large number of cutaneous lesions, including both surface damage and lumps under the skin (nodules). The moist tissues that line body openings such as the eyelids and the inside of the nose and mouth (mucous membranes) can also be affected, which can lead to vision loss, destruction of nasal tissue, or impaired speech. Some affected individuals have damage to internal organs and tissues. The nerve damage that occurs in multibacillary leprosy often results in a lack of sensation in the hands and feet. Repeated injuries that go unnoticed and untreated because of this lack of sensation can lead to reabsorption of affected fingers or toes by the body, resulting in the shortening or loss of these digits.
Paucibacillary leprosy typically involves a small number of surface lesions on the skin. There is generally loss of sensation in these areas, but the other signs and symptoms that occur in multibacillary leprosy are less likely to develop in this form of the disorder.
In any form of leprosy, episodes called reactions can occur, and can lead to further nerve damage. These episodes can include reversal reactions, which involve pain and swelling of the skin lesions and the nerves in the hands and feet. People with the more severe forms of leprosy can develop a type of reaction called erythema nodosum leprosum (ENL). These episodes involve fever and painful skin nodules. In addition, painful, swollen nerves can occur. ENL can also lead to inflammation of the joints, eyes, and the testicles in men.
Leprosy has long been stigmatized because of its infectious nature and the disfigurement it can cause. This stigma can cause social and emotional problems for affected individuals. However, modern treatments can prevent leprosy from getting worse and spreading to other people. While the infection is curable, nerve and tissue damage that occurred before treatment is generally permanent.
## Frequency
About 250,000 new cases of leprosy are diagnosed every year. The condition occurs worldwide, but is most common in India, Brazil, and other areas with warm climates. Between 100 and 250 new cases per year occur in the United States.
## Causes
Combinations of many variations in genes involved in the immune system affect a person's likelihood of contracting Mycobacterium leprae infection if exposed to the bacteria. Gene variations affecting the immune system also help determine the form of leprosy that individuals develop if the Mycobacterium leprae infection takes hold.
The body's initial, nonspecific response to an invading organism (innate immune response) is its first line of defense against Mycobacterium leprae. If this is followed by an immune system response specific to Mycobacterium leprae infection (adaptive immune response) that restricts the spread of the bacteria, an individual will probably develop the less severe paucibacillary form or not develop leprosy at all. If little or no adaptive immune response occurs, the bacteria can spread widely on the body, traveling through the skin and into the peripheral nerves, and sometimes into deeper tissues, leading to the more severe signs and symptoms of multibacillary leprosy.
Variations in immune system-related genes also affect the likelihood of developing episodes of reaction. Reactions occur when the immune system generates inflammation in response to dead bacteria that are still in the body.
The genes involved in leprosy provide instructions for making proteins that are involved in immune system processes such as recognition of the bacteria, immune system signaling, initiation of inflammation by the innate immune system, and production by the adaptive immune system of immune proteins (antibodies) specific to Mycobacteria leprae. The combined effect of the gene variations, as well as nongenetic factors that are not well understood, determine the effectiveness of these processes and the individual's vulnerability to leprosy.
### Learn more about the genes associated with Leprosy
* PRKN
* VDR
Additional Information from NCBI Gene:
* LTA
* PACRG
* TLR1
* TLR2
## Inheritance Pattern
Leprosy is not inherited, but people can inherit an increased risk of contracting leprosy if they are exposed to the Mycobacterium leprae bacteria. Susceptibility tends to run in families, but the inheritance pattern is unknown.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Leprosy
|
c1835932
| 7,334 |
medlineplus
|
https://medlineplus.gov/genetics/condition/leprosy/
| 2021-01-27T08:25:26 |
{"gard": ["6886"], "omim": ["609888", "607572", "246300", "610988", "613223", "613407"], "synonyms": []}
|
Facial nerve paralysis
Other namesFacial palsy, prosopoplegia[1]
Moche culture representation of facial paralysis. 300 AD, Larco Museum Collection, Lima, Peru
SpecialtyNeurology
Facial nerve paralysis is a common problem that involves the paralysis of any structures innervated by the facial nerve. The pathway of the facial nerve is long and relatively convoluted, so there are a number of causes that may result in facial nerve paralysis.[2] The most common is Bell's palsy,[3][4] a disease of unknown cause that may only be diagnosed by exclusion of identifiable serious causes.
## Contents
* 1 Signs and symptoms
* 2 Causes
* 2.1 Bell's palsy
* 2.2 Infection
* 2.3 Trauma
* 2.4 Tumors
* 2.5 Stroke
* 2.6 Other
* 3 Diagnosis
* 3.1 Classification
* 3.1.1 Supranuclear and nuclear lesions
* 3.1.2 Infranuclear lesions
* 4 Treatment
* 5 References
* 6 External links
## Signs and symptoms[edit]
Facial nerve paralysis is characterised by facial weakness, usually only in one side of the face, with other symptoms possibly including loss of taste, hyperacusis and decreased salivation and tear secretion. Other signs may be linked to the cause of the paralysis, such as vesicles in the ear, which may occur if the facial palsy is due to shingles. Symptoms may develop over several hours.[5] :1228 Acute facial pain radiating from the ear may precede the onset of other symptoms.[6] :2585
## Causes[edit]
### Bell's palsy[edit]
Main article: Bell's palsy
Bell's palsy is the most common cause of acute facial nerve paralysis.[3][4] There is no known cause of Bell's palsy,[5][6] although it has been associated with herpes simplex infection. Bell's palsy may develop over several days, and may last several months, in the majority of cases recovering spontaneously. It is typically diagnosed clinically, in patients with no risk factors for other causes, without vesicles in the ear, and with no other neurological signs. Recovery may be delayed in the elderly, or those with a complete paralysis. Bell's palsy is often treated with corticosteroids.[5][6]
### Infection[edit]
Lyme disease, an infection caused by Borrelia burgdorferi bacteria and spread by ticks, can account for about 25% of cases of facial palsy in areas where Lyme disease is common.[7] In the U.S., Lyme is most common in the New England and Mid-Atlantic states and parts of Wisconsin and Minnesota, but it is expanding into other areas.[8] The first sign of about 80% of Lyme infections, typically one or two weeks after a tick byte, is usually an expanding rash that may be accompanied by headaches, body aches, fatigue, or fever.[9] In up to 10-15% of Lyme infections, facial palsy appears several weeks later, and may be the first sign of infection that is noticed, as the Lyme rash typically does not itch and is not painful. Lyme disease is treated with antibiotics.[10][11]
Reactivation of herpes zoster virus, as well as being associated with Bell's palsy, may also be a direct cause of facial nerve palsy. Reactivation of latent virus within the geniculate ganglion is associated with vesicles affecting the ear canal, and termed Ramsay Hunt syndrome type II.[6] In addition to facial paralysis, symptoms may include ear pain and vesicles, sensorineural hearing loss, and vertigo. Management includes Antiviral drugs and oral steroids.
Otitis media is an infection in the middle ear, which can spread to the facial nerve and inflame it, causing compression of the nerve in its canal. Antibiotics are used to control the otitis media, and other options include a wide myringotomy (an incision in the tympanic membrane) or decompression if the patient does not improve. Chronic otitis media usually presents in an ear with chronic discharge (otorrhea), or hearing loss, with or without ear pain (otalgia). Once suspected, there should be immediate surgical exploration to determine if a cholesteatoma has formed as this must be removed if present. Inflammation from the middle ear can spread to the canalis facialis of the temporal bone - through this canal travels the facial nerve together with the statoacoustisus nerve. In the case of inflammation the nerve is exposed to edema and subsequent high pressure, resulting in a periferic type palsy.
### Trauma[edit]
In blunt trauma, the facial nerve is the most commonly injured cranial nerve.[12] Physical trauma, especially fractures of the temporal bone, may also cause acute facial nerve paralysis. Understandably, the likelihood of facial paralysis after trauma depends on the location of the trauma. Most commonly, facial paralysis follows temporal bone fractures, though the likelihood depends on the type of fracture.
Transverse fractures in the horizontal plane present the highest likelihood of facial paralysis (40-50%). Patients may also present with blood behind the tympanic membrane, sensory deafness, and vertigo; the latter two symptoms due to damage to vestibulocochlear nerve and the inner ear. Longitudinal fracture in the vertical plane present a lower likelihood of paralysis (20%). Patients may present with blood coming out of the external auditory meatus), tympanic membrane tear, fracture of external auditory canal, and conductive hearing loss. In patients with mild injuries, management is the same as with Bell's palsy – protect the eyes and wait. In patients with severe injury, progress is followed with nerve conduction studies. If nerve conduction studies show a large (>90%) change in nerve conduction, the nerve should be decompressed. The facial paralysis can follow immediately the trauma due to direct damage to the facial nerve, in such cases a surgical treatment may be attempted. In other cases the facial paralysis can occur a long time after the trauma due to oedema and inflammation. In those cases steroids can be a good help.
### Tumors[edit]
A tumor compressing the facial nerve anywhere along its complex pathway can result in facial paralysis. Common culprits are facial neuromas, congenital cholesteatomas, hemangiomas, acoustic neuromas, parotid gland neoplasms, or metastases of other tumours.[13][14]
Often, since facial neoplasms have such an intimate relationship with the facial nerve, removing tumors in this region becomes perplexing as the physician is unsure how to manage the tumor without causing even more palsy. Typically, benign tumors should be removed in a fashion that preserves the facial nerve, while malignant tumors should always be resected along with large areas of tissue around them, including the facial nerve. While this will inevitably lead to heightened paralysis, safe removal of a malignant neoplasm is worth the often treatable palsy that follows. In the best case scenario, paralysis can be corrected with techniques including hypoglossal-facial nerve anastomosis, end-to-end nerve repair, cross facial nerve grafting, or muscle transfer/transposition techniques, such as the gracilis free muscle transfer.
Patients with facial nerve paralysis resulting from tumours usually present with a progressive, twitching paralysis, other neurological signs, or a recurrent Bell's palsy-type presentation. The latter should always be suspicious, as Bell's palsy should not recur. A chronically discharging ear must be treated as a cholesteatoma until proven otherwise; hence, there must be immediate surgical exploration. Computed tomography (CT) or magnetic resonance (MR) imaging should be used to identify the location of the tumour, and it should be managed accordingly.
Other neoplastic causes include leptomeningeal carcinomatosis.
### Stroke[edit]
Central facial palsy can be caused by a lacunar infarct affecting fibers in the internal capsule going to the nucleus. The facial nucleus itself can be affected by infarcts of the pontine arteries. Unlike peripheral facial palsy, central facial palsy does not affect the forehead, because the forehead is served by nerves coming from both motor cortexes.[7]
### Other[edit]
Other causes may include:
* Diabetes mellitus[6]
* Facial nerve paralysis, sometimes bilateral, is a common manifestation of sarcoidosis of the nervous system, neurosarcoidosis.[6]
* Bilateral facial nerve paralysis may occur in Guillain–Barré syndrome, an autoimmune condition of the peripheral nervous system.[6]
* Moebius syndrome is a bilateral facial paralysis resulting from the underdevelopment of the VII cranial nerve (facial nerve), which is present at birth. The VI cranial nerve, which controls lateral eye movement, is also affected, so people with Moebius syndrome cannot form facial expression or move their eyes from side to side. Moebius syndrome is extremely rare, and its cause or causes are not known.
* Facial piercings, namely eyebrow piercings or tongue piercings, can in very rare cases cause damage to the facial nerve.
## Diagnosis[edit]
A medical history and physical examination, including a neurological examination, are needed for diagnosis. The first step is to observe what parts of the face do not move normally when the person tries to smile, blink, or raise the eyebrows. If the forehead wrinkles normally, a diagnosis of central facial palsy is made, and the person should be evaluated for stroke.[7] Otherwise, the diagnosis is peripheral facial palsy, and its cause needs to be identified, if possible. Ramsey Hunt's syndrome causes pain and small blisters in the ear on the same side as the palsy. Otitis media, trauma, or post-surgical complications may alternatively become apparent from history and physical examination. If there is a history of trauma, or a tumour is suspected, a CT scan or MRI may be used to clarify its impact. Blood tests or x-rays may be ordered depending on suspected causes.[6] The likelihood that the facial palsy is caused by Lyme disease should be estimated, based on recent history of outdoor activities in likely tick habitats during warmer months, recent history of rash or symptoms such as headache and fever, and whether the palsy affects both sides of the face (much more common in Lyme than in Bell's palsy). If that likelihood is more than negligible, a serological test for Lyme disease should be performed. If the test is positive, the diagnosis is Lyme disease. If no cause is found, the diagnosis is Bell's Palsy.
### Classification[edit]
The facial nerve
Facial nerve paralysis may be divided into supranuclear and infranuclear lesions. In a clinical setting, other commonly used classifications include: intra-cranial and extra-cranial; acute, subacute and chronic duration.[15]
#### Supranuclear and nuclear lesions[edit]
Central facial palsy can be caused by a lacunar infarct affecting fibers in the internal capsule going to the nucleus. The facial nucleus itself can be affected by infarcts of the pontine arteries. These are corticobulbar fibers travelling in internal capsule.
#### Infranuclear lesions[edit]
Infranuclear lesions refer to the majority of causes of facial palsy.
## Treatment[edit]
If an underlying cause has been found for the facial palsy, it should be treated. If it is estimated that the likelihood that the facial palsy is caused by Lyme disease exceeds 10%, empiric therapy with antibiotics should be initiated, without corticosteroids, and reevaluated upon completion of laboratory tests for Lyme disease.[7] All other patients should be treated with corticosteroids and, if the palsy is severe, antivirals. Facial palsy is considered severe if the person is unable to close the affected eye completely or the face is asymmetric even at rest. Corticosteroids initiated within three days of Bell's palsy onset have been found to increase chances of recovery, reduce time to recovery, and reduce residual symptoms in case of incomplete recovery.[7] However, for facial palsy caused by Lyme disease, corticosteroids have been found in some studies to harm outcomes.[7] Other studies have found antivirals to possibly improve outcomes relative to corticosteroids alone for severe Bell's palsy.[7] In those whose blinking is disrupted by the facial palsy, frequent use of artificial tears while awake is recommended, along with ointment and a patch or taping the eye closed when sleeping.[7][16]
## References[edit]
1. ^ "prosopoplegia". The Free Dictionary. Retrieved 1 January 2018.
2. ^ "Facial Nerve". Retrieved 22 November 2009.
3. ^ a b Fuller, G; Morgan, C (31 March 2016). "Bell's palsy syndrome: mimics and chameleons". Practical Neurology. 16 (6): 439–44. doi:10.1136/practneurol-2016-001383. PMID 27034243. S2CID 4480197.
4. ^ a b Dickson, Gretchen (2014). Primary Care ENT, An Issue of Primary Care: Clinics in Office Practice. Elsevier Health Sciences. p. 138. ISBN 978-0323287173. Archived from the original on 20 August 2016.
5. ^ a b c Colledge, Nicki R.; Walker, Brian R.; Ralston, Stuart H., eds. (2010). Davidson's principles and practice of medicine. illust. Robert Britton (21st ed.). Edinburgh: Churchill Livingstone/Elsevier. ISBN 978-0-7020-3084-0.
6. ^ a b c d e f g h Fauci, Anthony S.; Harrison, T. R., eds. (2008). Harrison's principles of internal medicine (17th ed.). New York: McGraw-Hill Medical. ISBN 978-0-07-147693-5.
7. ^ a b c d e f g h Garro A, Nigrovic LE (May 2018). "Managing Peripheral Facial Palsy". Annals of Emergency Medicine. 71 (5): 618–623. doi:10.1016/j.annemergmed.2017.08.039. PMID 29110887.
8. ^ "Lyme Disease Data and surveillance". Lyme Disease. Centers for Disease Control and Prevention. Retrieved 12 April 2019.
9. ^ "Lyme disease rashes and look-alikes". Lyme Disease. Centers for Disease Control and Prevention. Retrieved 18 April 2019.
10. ^ Wright WF, Riedel DJ, Talwani R, Gilliam BL (June 2012). "Diagnosis and management of Lyme disease". American Family Physician. 85 (11): 1086–93. PMID 22962880. Archived from the original on 27 September 2013.
11. ^ Shapiro ED (May 2014). "Clinical practice. Lyme disease" (PDF). The New England Journal of Medicine. 370 (18): 1724–1731. doi:10.1056/NEJMcp1314325. PMC 4487875. PMID 24785207. Archived from the original (PDF) on 19 October 2016.
12. ^ Cools MJ, Carneiro KA (April 2018). "Facial nerve palsy following mild mastoid trauma on trampoline". Am J Emerg Med. doi:10.1016/j.ajem.2018.04.034. PMID 29861376.
13. ^ Thompson AL, Bharatha A, Aviv RI, Nedzelski J, Chen J, Bilbao JM, Wong J, Saad R, Symons SP (July 2009). "Chondromyoid fibroma of the mastoid facial nerve canal mimicking a facial nerve schwannoma". Laryngoscope. 119 (7): 1380–1383. doi:10.1002/lary.20486.
14. ^ Thompson AL, Aviv RI, Chen JM, Nedzelski JM, Yuen HW, Fox AJ, Bharatha A, Bartlett ES, Symons SP (December 2009). "MR imaging of facial nerve schwannoma". Laryngoscope. 119 (12): 2428–2436. doi:10.1002/lary.20644.
15. ^ [1] The Plastics Fella Guide to Facial Nerve Anatomy
16. ^ Michelle Stephenson (4 October 2012). "OTC Drops: Telling the Tears Apart". Review of Ophtalmology. Jobson Medical Information LLC. Retrieved 16 April 2019.
## External links[edit]
Classification
D
* ICD-10: G51
* ICD-9-CM: 351
* MeSH: D005158
* SNOMED CT: 46382007
External resources
* MedlinePlus: 003028
* eMedicine: plastic/522
* v
* t
* e
Cranial nerve disease
Olfactory
*
Optic
*
Oculomotor
* Oculomotor nerve palsy
Trochlear
* Trochlear nerve palsy
Trigeminal
* Trigeminal neuralgia
Abducens
* Abducens nerve palsy
Facial
* Central facial palsy
* Facial nerve paralysis
* Bell's palsy
Vestibulocochlear
*
Glossopharyngeal
*
Vagus
*
Accessory
* Accessory nerve disorder
Hypoglossal
*
Combined syndromes
* Bulbar palsy
* Jugular foramen syndrome
* Cavernous sinus thrombosis
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Facial nerve paralysis
|
c0015469
| 7,335 |
wikipedia
|
https://en.wikipedia.org/wiki/Facial_nerve_paralysis
| 2021-01-18T18:34:48 |
{"mesh": ["D005158"], "umls": ["C0015469", "C0427055"], "icd-9": ["351"], "wikidata": ["Q7562539"]}
|
Congenital extreme form of developmental delay and neoteny
Neotenic complex syndrome
Other namesSyndrome X
Usual onsetUsually detected at or after age 3, but likely present at birth
CausesPossibly genetic (de novo mutations)
FrequencyExtremely rare: less than 100 confirmed cases worldwide
Neotenic complex syndrome (NCS) is a syndrome that presents as an extreme form of developmental delay, with the defining characteristic being neoteny of the patient. It was named in 2017 by Dr. Richard F. Walker, who discovered several genes implicated in the syndrome.[1]
Prior to 2015, when whole genome sequencing was used to identify some genes involved in NCS, the condition was labelled "Syndrome X" when it was first discovered in Brooke Greenberg. Thereafter, others afflicted with the developmental symptoms were sought out in order to find common genetic aberrations that could provide clues as to cause. To date, seven human females have been diagnosed with NCS. In five patients, coding de novo mutations were found in five different genes which fall into similar functional categories of transcription regulation and chromatin modification.[2][1]
## Genetics[edit]
In most of the patients analyzed, researchers identified missense de novo mutations in a set of genes. Mutations in three of these genes (DDX3X, TLK2 and HDAC8) were shared with those found in databases of individuals with developmental delay or autism spectrum disorder. A mutation in one gene (TMEM63B) was identified in a large knockout mouse study as likely to result in disease in humans. In two patients, a small (~150 kb) non-coding region of chromosome X was discovered to have a rare haplotype. This region appears to have regulatory functions (histone acetylation and DNase I hypersensitivity) and is in close proximity to several genes (AP1S2, MRX59, MRXSF, MRXS21, MRXS5 and PGS) involved in mental retardation. The fact that NCS has so far only been found in females may be by chance or may be due to the X linkage of some of the genes and regions potentially responsible for NCS, in which the lack of a healthy copy on a second X chromosome could render the disease lethal in males.[1]
Whether or not these mutations contribute to NCS is unclear. Not enough research has been conducted, complicated by the rarity of the syndrome. Many genetic differences were noted to be insignificant, and the effects of mutations in some genes are currently beyond scientific understanding.[1][3]
## Prominent cases[edit]
* Brooke Greenberg
## References[edit]
1. ^ a b c d Walker, Richard F.; Ciotlos, Serban; Mao, Qing; Chin, Robert; Drmanac, Snezana; Barua, Nina; Agarwal, Misha R.; Rebecca, Yu Zhang; Zhenyu, Li; Ka Yan Wu, Michelle; Sun, Kevin; Lee, Katharine; Nguyen, Staci; Liu, Jia Sophie; Carnevali, Paolo; Drmanac, Radoje; Peters, Brock A. (September 21, 2017). "Clinical and genetic analysis of a rare syndrome associated with neoteny". Genetics in Medicine. 20 (5): 495–502. doi:10.1038/gim.2017.140. PMID 29758565.
2. ^ Walker, Richard F.; Liu, Jia Sophie; Peters, Brock A.; Ritz, Beate R.; Wu, Timothy; Ophoff, Roel A.; Horvath, Steve (May 15, 2015). "Epigenetic age analysis of children who seem to evade aging". Aging (Albany NY). 7 (5): 334–339. doi:10.18632/aging.100744. PMC 4468314. PMID 25991677.
3. ^ "Whole Genome Sequencing Helps to Redefine a Rare Syndrome Associated with Neoteny". Genomics, October 5, 2017.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Neotenic complex syndrome
|
None
| 7,336 |
wikipedia
|
https://en.wikipedia.org/wiki/Neotenic_complex_syndrome
| 2021-01-18T19:00:49 |
{"wikidata": ["Q55624965"]}
|
## Summary
### Clinical characteristics.
Untreated tyrosinemia type I usually presents either in young infants with severe liver involvement or later in the first year with liver dysfunction and renal tubular dysfunction associated with growth failure and rickets. Untreated children may have repeated, often unrecognized, neurologic crises lasting one to seven days that can include change in mental status, abdominal pain, peripheral neuropathy, and/or respiratory failure requiring mechanical ventilation. Death in the untreated child usually occurs before age ten years, typically from liver failure, neurologic crisis, or hepatocellular carcinoma. Combined treatment with nitisinone and a low-tyrosine diet has resulted in a greater than 90% survival rate, normal growth, improved liver function, prevention of cirrhosis, correction of renal tubular acidosis, and improvement in secondary rickets.
### Diagnosis/testing.
Tyrosinemia type I results from deficiency of the enzyme fumarylacetoacetase (FAH). The diagnosis is established in a proband with typical biochemical findings (increased succinylacetone concentration in the blood and urine; elevated plasma concentrations of tyrosine, methionine, and phenylalanine; and elevated urinary concentration of tyrosine metabolites and the compound δ-ALA) and/or by the identification of biallelic pathogenic variants in FAH on molecular genetic testing.
### Management.
Treatment of manifestations: Nitisinone (Orfadin®), 2-(2-nitro-4-trifluoro-methylbenzyol)-1,3 cyclohexanedione (NTBC), which blocks parahydroxyphenylpyruvic acid dioxygenase (p-HPPD), the second step in the tyrosine degradation pathway, prevents the accumulation of fumarylacetoacetate and its conversion to succinylacetone. Nitisinone treatment should begin as soon as the diagnosis of tyrosinemia type I is confirmed. Because nitisinone increases the blood concentration of tyrosine, dietary management with controlled intake of phenylalanine and tyrosine should be started immediately after diagnosis to prevent tyrosine crystals from forming in the cornea. If the blood concentration of phenylalanine becomes too low (<20 μmol/L), additional natural protein should be added to the diet. Prior to the availability of nitisinone, the only definitive therapy for tyrosinemia type I was liver transplantation, which now should be reserved for those children who have severe liver failure at presentation and fail to respond to nitisinone therapy or have documented evidence of malignant changes in hepatic tissue.
Prevention of primary manifestations: Initiation of treatment with nitisinone as soon as the diagnosis is confirmed.
Prevention of secondary complications: Treatment of early signs of carnitine deficiency, osteoporosis, and rickets that are secondary to renal tubular Fanconi syndrome.
Surveillance: Guidelines for routine surveillance of individuals with tyrosinemia type I have been established.
Agents/circumstances to avoid: Inappropriate protein intake.
Evaluation of relatives at risk: All subsequent children of the parents of a child with tyrosinemia type I should have urine and blood succinylacetone analyzed as soon as possible after birth to enable the earliest possible diagnosis and initiation of therapy. If the pathogenic variants in the family are known, prenatal molecular genetic testing of an at-risk pregnancy may be considered.
Pregnancy management: Little data exist on the use of nitisinone during human pregnancy; however, at least two women have given birth to healthy infants while receiving therapeutic doses of nitisinone.
### Genetic counseling.
Tyrosinemia type I is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal diagnosis for pregnancies at increased risk are possible if both pathogenic variants in a family are known.
## Diagnosis
Tyrosinemia type I is caused by deficiency of the enzyme fumarylacetoacetase (FAH) (EC 3.7.1.2) (see Figure 1 and Pathophysiology).
#### Figure 1.
The tyrosine catabolic pathway
### Suggestive Findings
Tyrosinemia type I should be suspected in individuals with the following newborn screening results, clinical features, and supportive laboratory findings.
Newborn screening
* Presence of succinylacetone, measured directly from the newborn blood spot by tandem mass spectroscopy, is pathognomonic for tyrosinemia type 1.
* Elevated tyrosine or methionine concentration in the blood suggests liver disease, which can be from a variety of causes; the diagnosis of tyrosinemia type I should be further evaluated by quantification of plasma or urinary succinylacetone.
* Infants with tyrosinemia type I may have only modestly elevated or normal blood concentrations of tyrosine and methionine when the first newborn screening sample is collected.
* Elevated tyrosine concentration on newborn screening can be the result of transient tyrosinemia of the newborn, tyrosinemia type II or III, or other liver disease.
* Elevated methionine concentration can indicate liver dysfunction, defects in methionine metabolism, or homocystinuria (see Homocystinuria Caused by Cystathionine Beta-Synthetase Deficiency).
* Low delta-ALA-dehydratase (PBG synthase) enzyme activity. This is measured in the newborn screening program in Quebec, Canada [Giguère et al 2005]. Succinylacetone is then measured in the urine of infants with apparent δ-ALA dehydratase deficiency [Schulze et al 2001].
Clinical features (in untreated individuals)
* Severe liver disease in young infants
* Signs of renal disease, rickets, and/or neurologic crises in children older than age six months
Untreated children may have repeated neurologic crises lasting one to seven days that can include change in mental status, abdominal pain, peripheral neuropathy, and/or respiratory failure requiring mechanical ventilation.
Supportive laboratory findings
* Increased succinylacetone concentration in the blood and excretion in the urine
Note: (1) Increased excretion of succinylacetone in the urine of a child with liver failure or severe renal disease is a pathognomonic sign of tyrosinemia type I. (2) Many laboratories require that measurement of succinylacetone be specifically requested when ordering urine organic acids.
* Elevated plasma concentration of tyrosine, methionine, and phenylalanine
Note: (1) Plasma tyrosine concentration in affected infants can be normal in cord blood and during the newborn period. (2) Elevated plasma tyrosine concentration can also be a nonspecific indicator of liver damage or immaturity; for example, in infants taking a high-protein formula [Techakittiroj et al 2005], including undiluted goat's milk [Hendriksz & Walter 2004].
* Elevated urinary concentration of tyrosine metabolites p-hydroxyphenylpyruvate, p-hydroxyphenyllactate, and p-hydroxyphenylacetate detected on urine organic acid testing
* Increased urinary excretion of the compound δ-ALA secondary to inhibition of the enzyme δ-ALA dehydratase by succinylacetone in the liver and circulating red blood cells [Sassa & Kappas 1983]
* Changes in liver function (in untreated tyrosinemia type 1)
* Markedly elevated serum concentration of alpha-fetoprotein (average 160,000 ng/mL) (normal: <1,000 ng/mL for infants age 1-3 months; <12 ng/mL for children age 3 months to 18 years)
* Prolonged prothrombin and partial thromboplastin times
Note: (1) Changes in serum concentration of alpha-fetoprotein (AFP) and prothrombin time / partial thromboplastin time (PT/PTT) are more severe in tyrosinemia type I than in nonspecific liver disease and are often the presenting findings in tyrosinemia type I. (2) Transaminases and bilirubin are only modestly elevated, if at all. (3) An individual with liver disease and normal serum concentration of AFP and normal PT/PTT has a low probability of having tyrosinemia type I.
### Establishing the Diagnosis
The diagnosis of tyrosinemia type I is established in a proband with characteristic biochemical findings (increased succinylacetone concentration in the blood and urine; elevated plasma concentrations of tyrosine, methionine, and phenylalanine; and elevated urinary concentration of tyrosine metabolites and the compound δ-ALA) and/or by the identification of biallelic pathogenic variants in FAH on molecular genetic testing (see Table 1).
#### Molecular Genetic Testing
Single-gene testing. Sequence analysis of FAH is performed first and followed by gene-targeted deletion/duplication analysis if only one or no pathogenic variant is found.
* Targeted analysis for the p.Pro261Leu pathogenic variant can be performed first in individuals of Ashkenzai Jewish ancestry; this variant accounts for more than 99% of the pathogenic variants in this population [Elpeleg et al 2002].
* The pathogenic variant c.1062+5G>A (IVS12+5 G>A) accounts for 87.9% of pathogenic variants in the French Canadian population [Poudrier et al 1996].
* The four common FAH pathogenic variants – c.1062+5G>A (IVS12+5 G>A), c.554-1G>T (IVS6-1 G>T), c.607-6T>G (IVS7-6 T>G), and p.Pro261Leu – account for approximately 60% of pathogenic variants in tyrosinemia type I in the general US population [CR Scott, unpublished data].
### Table 1.
Molecular Genetic Testing Used in Tyrosinemia Type I
View in own window
Gene 1MethodProportion of Probands with Pathogenic Variants 2 Detectable by Method
FAHSequence analysis 3>95%
Gene-targeted deletion/duplication analysis 4Unknown; one reported large deletion 5
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants detected in this gene.
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
4\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
5\.
Park et al [2009] reported a large deletion involving FAH.
## Clinical Characteristics
### Clinical Description
For children who were not detected by newborn screening, tyrosinemia type I usually presents either in young infants with severe liver involvement or later in the first year with liver dysfunction and significant renal involvement, growth failure, and rickets. Growth failure results from chronic illness with poor nutritional intake, liver involvement, and/or chronic renal disease. Death in the undetected or untreated child usually occurs before age ten years, typically from liver failure, neurologic crisis, or hepatocellular carcinoma.
* Liver involvement. Undetected or untreated children presenting before age six months typically have acute liver failure with initial loss of synthetic function for clotting factors. PT and PTT are markedly prolonged and not corrected by vitamin K supplementation; factor II, VII, IX, XI, and XII levels are decreased; factor V and factor VIII levels are preserved. Paradoxically, serum transaminase levels may be only modestly elevated; serum bilirubin concentration may be normal or only slightly elevated, in contrast to most forms of severe liver disease in which marked elevation of transaminases and serum bilirubin concentration occur concomitantly with prolongation of PT and PTT. Resistance of affected liver cells to cell death may explain the observed discrepancy in liver function [Vogel et al 2004].
This early phase can progress to liver failure with ascites, jaundice, and gastrointestinal bleeding. Children may have a characteristic odor of "boiled cabbage" or "rotten mushrooms." Infants occasionally have persistent hypoglycemia; some have hyperinsulinism [Baumann et al 2005]. Others have chronic low-grade acidosis [CR Scott, unpublished data]. Untreated affected infants may die from liver failure within weeks or months of first symptoms [Hegarty et al 2015].
* Renal tubular involvement. In the more chronic form of the untreated disorder, symptoms develop after age six months; renal tubular involvement is the major manifestation. The renal tubular dysfunction involves a Fanconi-like renal syndrome with generalized aminoaciduria, phosphate loss, and, for many, renal tubular acidosis. The continued renal loss of phosphate is believed to account for rickets; serum calcium concentrations are usually normal.
* Neurologic crises. Untreated children may have repeated neurologic crises similar to those seen in older individuals with acute intermittent porphyria. These crises include change in mental status, abdominal pain, peripheral neuropathy, and/or respiratory failure requiring mechanical ventilation. Crises can last one to seven days. Repeated neurologic crises often go unrecognized:
* Mitchell et al [1990] reported that 42% of untreated French Canadian children with tyrosinemia type I had experienced such episodes.
* In an international survey, van Spronsen et al [1994] reported that 10% of deaths in untreated children occurred during a neurologic crisis.
* Hepatocellular carcinoma. Those children who are not treated with nitisinone and a low-tyrosine diet and who survive the acute onset of liver failure are at high risk of developing and succumbing to hepatocellular carcinoma.
* Survival in untreated children. Untreated infants diagnosed before age two months had a two-year survival rate of 29% [van Spronsen et al 1994].
* Those diagnosed between ages two and six months had a 74% two-year survival rate; those diagnosed after age six months had a 96% two-year survival rate.
* After more than five years the survival rate of the group diagnosed between ages two and six months dropped to approximately 30% and that of the group diagnosed after age six months dropped to approximately 60% (Figure 2).
#### Figure 2.
Survival of children with tyrosinemia before 1992 [van Spronsen et al 1994]
Treated tyrosinemia type I. The natural history in children who are treated with nitisinone is different from that in untreated children. Affected children younger than age two years who are treated with a combination of nitisinone and low-tyrosine diet are markedly improved compared to those children treated with low-tyrosine diet alone. The combined nitisinone and low-tyrosine diet treatment has resulted in a greater than 90% survival rate, normal growth, improved liver function, prevention of cirrhosis, correction of renal tubular acidosis, and improvement in secondary rickets [McKiernan 2006, Masurel-Paulet et al 2008, Larochelle et al 2012].
* Neurologic crises observed in treated children have always been associated with a prolonged interruption in nitisinone treatment [CR Scott, unpublished data].
* Children with acute liver failure require support prior to and during the initiation of treatment with nitisinone. Improvement generally occurs within one week of starting nitisinone treatment.
* Corneal crystals. Nitisinone blocks the tyrosine catabolic pathway such that succinylacetone is not produced but tissue tyrosine levels are raised. Blood tyrosine concentration greater than 600 mol/L confers risk of precipitation of tyrosine as bilateral, linear, branching subepithelial corneal opacities [Ahmad et al 2002], causing photophobia and itchy, sensitive eyes. The crystals resolve once tyrosine levels are reduced.
* Hepatocellular carcinoma. Although Holme & Lindstedt [2000] and van Spronsen et al [2005] reported hepatocellular carcinoma in individuals after years of nitisinone therapy, it is estimated that fewer than 5% of children placed on nitisinone therapy before age two years develop hepatocellular carcinoma by age ten years [Larochelle et al 2012].
In Quebec, where tyrosinemia type I is included in the newborn screening program, no affected individuals have been hospitalized for manifestations of tyrosinemia type I, and hepatocellular carcinoma has not been reported in individuals who were placed on nitisinone therapy prior to age 30 days. The longest period of treatment reported in this group is 12 years [Larochelle et al 2012].
### Pathophysiology
Fumarylacetoacetase (FAH) is the terminal enzyme in the tyrosine catabolic pathway (Figure 1). In FAH deficiency, fumarylacetoacetate (FAA), the immediate precursor:
* Appears to accumulate in hepatocytes, causing cellular damage and apoptosis (identified in an animal model by Endo & Sun [2002]);
* Is diverted into succinylacetoacetate and succinylacetone. Succinylacetone interferes with the activity of the following hepatic enzymes:
* Parahydroxyphenylpyruvic acid dioxygenase (p-HPPD), resulting in elevation of plasma tyrosine concentration;
* PBG synthase, resulting in (1) reduced activity of the enzyme δ-ALA dehydratase in liver and circulating red blood cells; (2) reduced heme synthesis; (3) increased δ-aminolevulinic acid (δ-ALA), which may induce acute neurologic episodes; and (4) increased urinary excretion of δ-ALA.
### Genotype-Phenotype Correlations
In general, no correlation is observed between clinical presentation and genotype. Acute and chronic forms have been seen in the same families, as well as in unrelated individuals with the same genotype [Poudrier et al 1998].
One mechanism that explains this clinical variation is gene reversion. Hepatic nodules removed from livers of individuals with the chronic form of tyrosinemia type I have been shown to have cells that are immunologically positive for FAH protein and to have enzymatic activity for FAH [Kvittingen et al 1994, Grompe 2001]. These seemingly "normal" cells appear to have arisen by gene reversion – that is, the spontaneous self-correction (i.e., reversion or "back-mutation") of the germline pathogenic variant to the normal gene sequence during somatic cell division.
Spontaneous somatic variants that suppress the effects of the pathogenic variants and allow for normal or near-normal gene expression in these cells have also been reported [Bliksrud et al 2005]. This is a true reversion of the mutated sequence and not the result of maternal cell colonization or maternal cell fusion [Bergeron et al 2004]. The "normal" (i.e., reverted) cells have a selective growth advantage because they are no longer at risk for apoptosis from the accumulation of FAA. These foci of revertant "normal" cell colonies comprise many of the liver nodules in untreated individuals with chronic tyrosinemia type I who have a milder biochemical and clinical phenotype [Kim et al 2000, Demers et al 2003]. However, the continued production of FAA by the non-revertant mutated cells places the individual at continued risk for hepatocellular carcinoma [Kim et al 2000].
A rare and atypical form of tyrosinemia type I has been reported in a four-month-old Belgian infant with severe liver disease. Liver function studies were abnormal with markedly elevated alpha-fetoprotein, prolonged PT and PTT, and undetectable succinylacetone in urine. Fumarylacetoacetase (FAH) protein and activity was decreased, but not absent. Homozygosity for a unique pathogenic variant, c.103G>A (p.Ala35Thr), was identified [Cassiman et al 2009].
Similarly, three sibs who developed chronic liver disease and HCC without detectable blood or urine succinylacetone had deficient FAH activity. The family was of Middle Eastern background and each child was homozygous for c.424A>G in FAH [Blackburn et al 2016].
### Nomenclature
The term " tyrosinosis" was previously used to refer to tyrosinemia type I include tyrosinosis.
### Prevalence
In geographic areas without newborn screening, tyrosinemia type I affects approximately one in 100,000 to 120,000 births [Mitchell et al 2001]. Because of the inconsistent and confusing nature of its clinical presentation, it is estimated that fewer than 50% of affected individuals are diagnosed while alive.
In the general US population, the carrier frequency is estimated at 1:150 to 1:100.
Two regions of the world have a higher than expected frequency of tyrosinemia type I due to the increased frequency of certain pathogenic variants resulting from a founder effect:
* In the Scandanavian countries (c.1062+5G>A (IVS 12+5 G>A), p.Gly337Ser, and/or p.249HisfsTer5.5) and in Finland (p.Trp262Ter), the birth prevalence is estimated at 1:74,000 and 1:60,000 live births, respectively [Bliksrud et al 2012].
* A founder effect from colonization by French settlers is present in the province of Quebec, Canada. The c.1062+5G>A (IVS12+5 G>A) pathogenic variant accounts for 87% of allelic variants in this population. The birth prevalence in the province of Quebec is 1:16,000. In the Saguenay-Lac Saint-Jean region of Quebec, it is 1:1,846 live births. The overall carrier frequency in Quebec is 1:66 based on newborn screening data. The carrier frequency in the Saguenay-Lac St-Jean region is 1:16-1:20.
## Differential Diagnosis
Children with any of the following presenting findings should be evaluated for tyrosinemia type I (Table 2):
### Table 2.
Differential Diagnosis of Tyrosinemia Type I in Infants by Presenting Finding
View in own window
Presenting FindingDifferential Diagnosis
Hypertyrosinemia
* Immature liver
* High-protein diet 1, 2
* Tyrosinemia type II (OMIM 276600)
* Tyrosinemia type III (OMIM 276710)
* Other liver disease
Hypermethioninemia
* Homocystinuria
* Disorders of methionine metabolism
* Other liver disease
Liver disease
* Galactosemia
* Hereditary fructose intolerance
* Fructose 1, 6 biphosphatase deficiency (OMIM 229700)
* Niemann-Pick disease type C
* Wilson disease
* Neonatal hemochromatosis (OMIM 231100)
* Hemophagocytic lymphohistiocytosis
* Mitochondrial cytopathies
* Congenital disorders of glycosylation
* Transaldolase deficiency (OMIM 606003)
* Acetaminophen toxicity
* Bacterial infections (sepsis, salmonella, TB)
* Viral infections (e.g., CMV, hepatitis A/B, herpes)
* Mushroom poisoning 3
* Herbal medicines 3
* Idiosyncratic drug reaction, toxin, vascular/ischemic or infiltrative process 3
Renal syndrome
* Lowe syndrome
* Cystinosis
* Renal tubular acidosis
* Fanconi syndrome
Rickets
* Hypophosphatasia
* Vitamin D deficiency (nutritional/genetic)
* Hypophosphatemic rickets
* Vitamin D-dependent rickets
* Fanconi syndrome
Neurologic crisis
* Cerebral hemorrhage/edema
* Bacterial/viral meningitis
* Hypernatremic dehydration
* Acute intermittent porphyria
1\.
Techakittiroj et al [2005]
2\.
Undiluted goat's milk [Hendriksz & Walter 2004]
3\.
Bansal & Dhawan [2004]
Tyrosinemia type II is caused by a defect in tyrosine aminotransferase (TAT) (EC 2.6.1.5). Establishing the diagnosis of tyrosinemia type II relies on the following:
* Plasma tyrosine concentration typically greater than 500 µmol/L that may exceed 1,000 µmol/L (The concentration of other amino acids is normal.)
* Increased excretion of p-hydroxyphenylpyruvate, p-hydroxyphenyllactate, and p-hydroxyphenylacetate and presence of small quantities of N-acetyltyrosine and 4-tyramine on urine organic acid analysis
Affected individuals have painful, non-pruritic, and hyperkeratotic plaques on the soles and palms. The plantar surface of the digits may show marked yellowish thickening associated with the hyperkeratosis. Ophthalmologic involvement is recalcitrant pseudodendritic keratitis [Macsai et al 2001]. Although developmental delay appears to be common, it is unclear if ascertainment bias accounts for this and the reports of neurologic symptoms.
Findings improve on a diet restricted in tyrosine and phenylalanine [Ellaway et al 2001].
Tyrosinemia type III, the rarest of the tyrosine disorders, is caused by a deficiency of p-hydroxyphenylpyruvic acid dioxygenase (EC.1.13.11.27). Plasma concentration of tyrosine ranges from 350 to 650 µmol/L. Excretion of 4-hydroxyphenylpyruvic acid, 4-hydroxyphenyllactate, and 4-hydroxyphenylacetate is increased. The precise quantities vary with protein intake.
Few individuals with the disorder have been identified, and the clinical phenotype remains ill defined. The first affected individuals came to medical attention because of intellectual disability or ataxia; another was detected on routine screening [Mitchell et al 2001]. These individuals, like those with tyrosinemia type II, have no liver involvement but have skin or ocular changes. It remains unclear if tyrosinemia type III is truly associated with cognitive delays or if the association has resulted from ascertainment bias [Ellaway et al 2001].
A diet low in phenylalanine and tyrosine can lower plasma tyrosine concentration.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs of a child diagnosed with tyrosinemia type I on the basis of newborn screening, the following evaluations are recommended (see Table 3):
* CBC with platelet count
* Serum concentration of electrolytes
* Assessment of liver function (PT, PTT, AST, ALT, GGT, serum bilirubin concentration, alkaline phosphatase, and serum AFP).
For children ascertained on the basis of clinical symptoms (see Table 4; pdf), testing should include the evaluations listed above in addition to:
* Baseline abdominal imagining by CT or MRI (with contrast) to evaluate for liver adenomas or nodules (see Dubois et al [1996]) and renal size;
* X-ray of wrist to document presence or absence of rickets.
Clinical genetics consultation is indicated for all affected individuals.
### Treatment of Manifestations
Management guidelines have been published. US recommendations include Chinsky et al [2017]; European recommendations include de Laet et al [2013].
Acute management of liver failure. Children may require respiratory support, appropriate fluid management, and blood products for correction of bleeding diathesis.
Nitisinone (Orfadin®). 2-(2-nitro-4-trifluoro-methylbenzyol) 1,3 cyclohexanedione (NTBC) blocks parahydroxyphenylpyruvic acid dioxygenase (p-HPPD), the second step in the tyrosine degradation pathway, and prevents the accumulation of FAA and its conversion to succinylacetone (Figure 1).
* Nitisinone should be prescribed as soon as the diagnosis of tyrosinemia type I is confirmed.
* Nitisinone is generally prescribed at 1.0 mg/kg/day; individual requirements may vary. Dosage should be adjusted to maintain blood nitisinone levels between 40 and 60 µmol/L, which theoretically blocks more than 99% of p-HPPD activity. Rarely, an individual may require higher blood levels of nitisinone (70 µmol/L) to suppress succinylacetone excretion. As long as blood concentration of nitisinone is within the therapeutic range, urine succinylacetone does not need to be measured.
* Nitisinone is typically given in two divided doses; however, because of the long half-life (50-60 hours), affected individuals who are older than one year and stable may maintain adequate therapy with 1x/day dosing [Schlune et al 2012].
* Rare side effects of nitisinone have included: transient low platelet count and transient low neutrophil count that resolved without intervention; and photophobia that resolved with stricter dietary control and subsequent lowering of blood tyrosine concentrations.
Low-tyrosine diet. Nitisinone increases blood concentration of tyrosine, necessitating a low-tyrosine diet to prevent tyrosine crystals from forming in the cornea.
* Dietary management should be started immediately upon diagnosis and should provide a nutritionally complete diet with controlled intakes of phenylalanine and tyrosine using a vegetarian diet with low-protein foods and a medical formula such as Tyrex® (Ross) or Tyros-1® (Mead Johnson).
* Phenylalanine and tyrosine requirements are interdependent and vary from individual to individual and within the same individual depending on growth rate, adequacy of energy and protein intakes, and state of health. With appropriate dietary management, plasma tyrosine concentration should be 300-600 µmol/L, regardless of age; plasma phenylalanine concentration should be 20-80 µmol/L (0.3-1.3 mg/dL). If the blood concentration of phenylalanine is too low (<20 µmol/L), additional protein should be added to the diet from milk or foods.
Liver transplantation. Prior to the availability of nitisinone for the treatment of tyrosinemia type I, the only definitive therapy was liver transplantation.
* Liver transplantation should be reserved for those children who (1) have severe liver failure at clinical presentation and fail to respond to nitisinone therapy or (2) have documented evidence of malignant changes in hepatic tissue [Bartlett et al 2014].
* Transplant recipients require long-term immunosuppression. Mortality associated with liver transplantation in young children is approximately 10%.
* Transplant recipients may also benefit from low-dose (0.1mg/kg/day) nitisinone therapy to prevent continued renal tubular and glomerular dysfunction resulting from persistence of succinylacetone in the plasma and urine [Bartlett et al 2013].
### Prevention of Primary Manifestations
Treatment with nitisinone (Orfadin®) should begin as soon as the diagnosis is confirmed.
### Prevention of Secondary Complications
Because carnitine deficiency secondary to the renal tubular Fanconi syndrome can cause skeletal muscle weakness, serum concentration of carnitine should be measured so that carnitine deficiency, if identified, can be treated [Nissenkorn et al 2001].
Osteoporosis and rickets resulting from renal tubular damage are treated by correction of acidosis, restoring of calcium and phosphate balance, and administration of 25-hydroxy-vitamin D.
### Surveillance
Frequent evaluation of the following parameters is typical in the management of individuals with tyrosinemia type I (Table 3) [CR Scott, personal recommendations].
### Table 3.
Suggested Guidelines for Monitoring in Individuals with Tyrosinemia Type I Diagnosed by Newborn Screening
View in own window
EvaluationInitiation of Therapy (Baseline)First 6 Mos:After 6 Mos of Rx: Every 6-12 MosAfter 2 Yrs of Rx: Every 6-12 MosAs Clinically Indicated
1x/MoEvery 3 Mos
Tyrosinemia type I markersPlasma concentration of methionine, phenylalanine, tyrosineXxXXor X
Blood / urine succinylacetoneXX
(urine)Xor X
Blood nitisinone concentrationXXXor X
CBCHemoglobin, hematocrit, WBC, platelet countXXXXor X
Liver
evaluationSerum AFP concentrationXXXXX
PT/PTTXX
(until normal)
BilirubinX
ALT/AST/GGTXX
(until normal)X
Alkaline phosphataseXX
(until normal)XX
CT or MRI 1X
Renal studiesBUN / creatinineX
Urine: PO4, Ca, Prot/Cr ratioX
Skeletal evaluationX-ray of wrist (for rickets)X
AFP = alpha-fetoprotein; ALT/AST = alanine transaminase/aspartate transaminase; BUN = blood urea nitrogen; CBC = complete blood count; GGT = gamma-glutamyl transferase; PT/PTT = prothrombin time/partial thromboplastin time
1\.
MRI with contrast to evaluate for liver adenomas or nodules and for kidney size
For monitoring children diagnosed based on clinical presention, see Table 4 (pdf).
For alternative management recommendations, see de Laet et al [2013].
### Agents/Circumstances to Avoid
Avoid inappropriate protein intake.
### Evaluation of Relatives at Risk
It is appropriate to evaluate apparently asymptomatic older and younger sibs of a proband in order to identify as early as possible those who would benefit from prompt initiation of treatment and preventive measures.
Evaluations can include:
* Molecular genetic testing if the pathogenic variants in the family are known. Prenatal testing can be used to clarify the genetic status of at-risk sibs before birth.
* Blood or urine succinylacetone analysis as soon as possible after birth if prenatal testing was not performed. This allows prompt initiation of treatment, as postnatal genetic testing results may not be available in a timely fashion.
* If the pathogenic variants in the family are not known, consideration of analysis for urine succinylacetone in healthy older sibs
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
Little data exist on the use of nitisinone during human pregnancy. Speculation would assume that the pregnant woman remains safe from untoward events; however, the developing fetus may be at risk because of alterations in tyrosine metabolism.
At least two women have given birth to healthy infants while receiving therapeutic doses of nitisinone [Garcia Segarra et al 2010].
* In one instance the affected mother gave birth to an unaffected infant who is reported to be healthy and developing normally at age 2.5 years [Garcia Segarra et al 2010, Vanclooster et al 2012].
* In another instance, an affected woman gave birth to an affected child. The child is reported to have normal growth and development at age seven months [Garcia Segarra et al 2010]. The authors speculate that the affected child was protected from in utero liver damage by maternal treatment with nitisinone during pregnancy.
See MotherToBaby for more information on medication exposure during pregnancy.
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
### Other
Prior to the availability of nitisinone, the only available non-transplant therapy was a diet limiting the availability of phenylalorine and tyrosine. Although the diet was modestly helpful, recurrent episodes of neurologic crises and progression of liver disease occurred. Average survival was less than age ten years.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Tyrosinemia Type I
|
c0268490
| 7,337 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK1515/
| 2021-01-18T20:51:56 |
{"mesh": ["D020176"], "synonyms": ["FAH Deficiency", "Fumarylacetoacetase Deficiency", "Fumarylacetoacetate Hydrolase Deficiency", "Hepatorenal Tyrosinemia"]}
|
Wallenberg syndrome is a condition that affects the nervous system. Signs and symptoms may include swallowing difficulties, dizziness, hoarseness, nausea and vomiting, nystagmus, and problems with balance. Some people have uncontrollable hiccups, loss of pain and temperature sensation on one side of the face, and/or weakness or numbness on one side of the body. Wallenberg syndrome is often caused by a stroke in the brain stem. Treatment addresses each symptom and may include a feeding tube for swallowing problems, speech and/or swallowing therapy, and medication for pain. While some people's symptoms may improve within weeks or months, others may have long-term neurological problems.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Wallenberg syndrome
|
c0043019
| 7,338 |
gard
|
https://rarediseases.info.nih.gov/diseases/9263/wallenberg-syndrome
| 2021-01-18T17:57:08 |
{"mesh": ["D014854"], "synonyms": ["Lateral medullary syndrome", "Posterior inferior cerebellar artery syndrome", "PICA syndrome", "Vertebral artery syndrome", "Wallenberg's syndrome"]}
|
Seijffers et al. (1964) described what they termed systemic venular insufficiency in a 40-year-old Ashkenazi Jew. Marked cyanosis and swelling of the head and neck followed bending over and the hands and feet were similarly affected when in the dependent position. Small veins and venules in conjunctiva showed marked dilation. Erection did not occur but could be induced by manual compression of the root of the penis. The authors suggested a venous defect, either absence of valves or absence of smooth muscle in the walls of small veins. The parents were first cousins and the father may have had the same disorder in milder form. Thus, the possibility of either recessive or dominant inheritance could be entertained.
Inheritance \- Autosomal dominant vs. recessive Vascular \- Systemic venular insufficiency \- Dependent cyanosis and swelling ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
VENULAR INSUFFICIENCY, SYSTEMIC
|
c1860465
| 7,339 |
omim
|
https://www.omim.org/entry/192700
| 2019-09-22T16:32:00 |
{"mesh": ["C566004"], "omim": ["192700"]}
|
## Description
Rupture of an intracranial aneurysm, an outpouching or sac-like widening of a cerebral artery, leads to a subarachnoid hemorrhage, a sudden-onset disease that can lead to severe disability and death. Several risk factors such as smoking, hypertension, and excessive alcohol intake are associated with subarachnoid hemorrhage (summary by Krischek and Inoue, 2006).
For a discussion of genetic heterogeneity of intracranial berry aneurysm, see ANIB1 (105800).
Mapping
The identification of 2 single-nucleotide polymorphisms (SNPs) on chromosome 9p21 in adjacent linkage disequilibrium blocks associated with type 2 diabetes (rs10811661; see 125853) and coronary artery disease (CAD) (rs10757278; see CHDS8, 611139 and Helgadottir et al., 2007) raised the possibility that a region on 9p21 could predispose to both disorders through a shared biologic mechanism. Helgadottir et al. (2008) investigated this possibility by genotyping these SNPs in Icelandic individuals with 1 of 5 arterial diseases or type 2 diabetes, as well as in several additional case-control sets of European descent with the same phenotypes. They found that, in addition to CAD, rs10757278-G was associated with abdominal aortic aneurysm (AAA3; 611891) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with type 2 diabetes. Assuming an allele frequency of 47.5% for rs10757278-G, Helgadottir et al. (2008) found the corresponding population-attributable risk for both intracranial aneurysm and AAA to be approximately 26%.
In a genomewide association study of 920 Finnish patients with intracranial aneurysm and 985 controls, Bilguvar et al. (2008) found a significant association with rs1333040 on chromosome 9p. The association was replicated in a Dutch cohort of 781 cases and 6,424 controls and a Japanese cohort of 495 cases and 676 controls. The combined p value was 1.4 x 10(-10) with an odds ratio of 1.29.
Yasuno et al. (2010) performed genomewide analysis of intracranial aneurysm in an expanded cohort from the study of Bilguvar et al. (2008) with discovery and replication cohorts from Europe and Japan comprising a total of 5,891 cases and 14,181 controls. Significant association was found with rs1333040 on chromosome 9p21.3 near CDKN2A (600160) and CDKN2B (600431) (odds ratio of 1.32, p = 1.5 x 10(-22)).
In a genomewide association study of 1,383 Japanese individuals with intracranial aneurysm and 5,484 controls, Low et al. (2012) found a significant association with rs10757272 within the CDKN2BAS gene (613149) on chromosome 9p21.3 (p = 7.75 x 10(-4)). The association with this SNP was replicated in an independent cohort of 1,048 patients and 7,212 controls (corrected p less than 1.16 x 10(-3)). The combined p value for this SNP was 1.55 x 10(-7), with an OR of 1.21.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
ANEURYSM, INTRACRANIAL BERRY, 6
|
c1862932
| 7,340 |
omim
|
https://www.omim.org/entry/611892
| 2019-09-22T16:02:46 |
{"doid": ["0060228"], "mesh": ["C566284"], "omim": ["105800", "611892"], "orphanet": ["231160"], "synonyms": ["Familial berry aneurysm", "Familial intracranial saccular aneurysm"]}
|
A rare radiation-induced disorder characterized by exposed irradiated bone that fails to heal over a period of three months without evidence of persisting or recurrent tumor. Patients present with pain, dysesthesia, dysgeusia, fetor oris, trismus, ulceration or necrosis of the mucosa with exposure of necrotic bone, and local suppuration. Complications include pathological fractures, formation of intra- or extra-oral fistulae, and infection. MRI shows cortical destruction, abnormal bone marrow signal, and irregular contrast enhancement.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Osteoradionecrosis of the mandible
|
c1290728
| 7,341 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=521127
| 2021-01-23T17:51:45 |
{}
|
## Summary
### Clinical characteristics.
Cantú syndrome is characterized by congenital hypertrichosis; distinctive coarse facial features (including broad nasal bridge, wide mouth with full lips and macroglossia); enlarged heart with enhanced systolic function or pericardial effusion and in many, a large patent ductus arteriosus (PDA) requiring repair; and skeletal abnormalities (thickening of the calvaria, broad ribs, scoliosis, and flaring of the metaphyses). Other cardiovascular abnormalities may include dilated aortic root and ascending aorta with rare aortic aneurysm, tortuous vascularity involving brain and retinal vasculature, and pulmonary arteriovenous communications. Generalized edema (which may be present at birth) spontaneously resolves; peripheral edema of the lower extremities (and sometimes arms and hands) may develop at adolescence. Developmental delays are common, but intellect is typically normal; behavioral problems can include attention-deficit/hyperactivity disorder, autism spectrum disorder, obsessive-compulsive disorder, anxiety, and depression.
### Diagnosis/testing.
The diagnosis of Cantú syndrome is established in a proband with suggestive clinical findings and a heterozygous pathogenic variant in ABCC9 or KCNJ8 identified by molecular genetic testing. Some individuals with a clinical diagnosis of Cantú syndrome have not had a pathogenic variant identified in either gene, suggesting the existence of another as-yet unidentified causative gene.
### Management.
Treatment of manifestations: Surgical or device closure of PDA in infancy or early childhood as needed. Pericardiocentesis and pericardial stripping as needed to treat pericardial effusion. Compression stockings for peripheral edema; shaving and (in teenagers and adults) use of depilatories or laser hair removal for hypertrichosis; bracing and/or surgery as needed for scoliosis; individualized management for migraine headaches and developmental delays if present.
Surveillance: Yearly echocardiogram and electrocardiogram to monitor cardiac size and function, as well as for evidence of pericardial effusion. Clinical evaluation and cardiac biomarkers to monitor late development of high-output cardiac failure. Monitor for evidence of peripheral edema annually starting in adolescence and for scoliosis with physical examination, followed by spine radiographs as needed. Monitor for a history of persistent headaches or other neurologic symptoms, which may require brain imaging for cerebral vasculature abnormality and evaluation by a neurologist.
Evaluation of relatives at risk: If the pathogenic variant in an affected family member is known, relatives at risk who are suspected of having Cantú syndrome can be offered molecular genetic testing to clarify their genetic status. Family members who are affected should be evaluated and monitored for cardiac manifestations, scoliosis, and peripheral edema.
### Genetic counseling.
Cantú syndrome is inherited in an autosomal dominant manner. Each child of an individual with Cantú syndrome has a 50% chance of inheriting the pathogenic variant and being affected. Prenatal and preimplantation genetic testing are possible if the pathogenic variant has been identified in an affected family member.
## Diagnosis
No formal diagnostic criteria for Cantú syndrome have been established.
### Suggestive Findings
Cantú syndrome should be suspected in individuals with a combination of the following:
* Congenital hypertrichosis: excess hair growth on scalp, forehead, face, back, and limbs (see Figure 1 and Figure 2)
* Craniofacial dysmorphic features: coarse facial features, epicanthal folds, broad nasal bridge, anteverted nares, long philtrum, macroglossia, wide mouth, and full lips (see Figure 1)
* Enlarged heart with enhanced systolic function or pericardial effusion (see Figure 3 and Figure 4)
* Large patent ductus arteriosus (PDA) requiring repair
* Characteristic skeletal abnormalities: thickening of the calvaria (see Figure 3), broad ribs, platyspondyly, ovoid vertebral bodies, scoliosis, narrow thorax and shoulders, pectus carinatum, hypoplastic ischium and pubic bones, Erlenmeyer-flask-like long bones with metaphyseal flaring (see Figure 3 and Figure 4), narrow obturator foramen, and coxa vara
#### Figure 1.
Woman age 40 years (A, D), girl age 16 years (B, E), and girl age 11 years (C, F) with Cantù syndrome A, B, C. Facial appearance showing hirsutism of the forehead with low frontal hairline and coarse features
#### Figure 2.
Girl age 11 years (A, B) and girl age 16 years (C) with Cantù syndrome A. Narrow thorax and pectus carinatum deformity
#### Figure 3.
Woman age 40 years with Cantù syndrome A. Chest x-ray showing marked cardiomegaly
#### Figure 4.
Girl age 16 years with Cantù syndrome A. Chest x-ray showing cardiomegaly
### Establishing the Diagnosis
The diagnosis of Cantú syndrome is established in a proband with suggestive clinical findings and a heterozygous pathogenic variant in ABCC9 or KCNJ8 identified by molecular genetic testing (see Table 1).
Molecular genetic testing approaches can include a combination of gene-targeted testing (multigene panel) and comprehensive genomic testing (exome sequencing, exome array, genome sequencing) depending on the phenotype.
Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Individuals with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those in whom the diagnosis of Cantú syndrome has not been considered are more likely to be diagnosed using genomic testing (see Option 2).
#### Option 1
When the phenotypic findings suggest the diagnosis of Cantú syndrome, molecular genetic testing approaches can include use of a multigene panel.
A multigene panel that includes the genes listed in Table 1 and other genes of interest (see Differential Diagnosis) is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
#### Option 2
When the diagnosis of Cantú syndrome is unclear because an individual has atypical phenotypic features, comprehensive genomic testing (which does not require the clinician to determine which gene[s] are likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible.
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
Note: All pathogenic variants reported to date are gain-of-abnormal-function variants in ABCC9 and KCNJ8; thus, testing for deletion (haploinsufficiency) or duplication (overexpression) is not indicated.
### Table 1.
Molecular Genetic Testing Used in Cantú Syndrome
View in own window
Gene 1, 2Proportion of Cantú Syndrome Attributed to Pathogenic Variants in Gene 6Proportion of Probands with a Pathogenic Variant 3 Detectable by Method
Sequence
analysis 4Gene-targeted deletion/duplication analysis 5
ABCC997%100% 6Not applicable 7
KCNJ81%-2%3/3 tested 8Not applicable 7
Unknown 9NA
1\.
Genes are listed in alphabetic order.
2\.
See Table A. Genes and Databases for chromosome locus and protein.
3\.
See Molecular Genetics for information on variants detected in these genes.
4\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
5\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
6\.
Grange et al [2019]
7\.
All pathogenic variants reported to date are gain-of-abnormal-function variants in ABCC9 and KCNJ8; thus, testing for deletion (haploinsufficiency) or duplication (overexpression) is not indicated.
8\.
Brownstein et al [2013], Cooper et al [2014], Chihara et al [2020]
9\.
A small number (<1%) of individuals with a clinical diagnosis of Cantú syndrome in whom no ABCC9 or KCNJ8 variant was found raises the possibility that other as-yet unidentified genes may be involved [DK Grange, personal observation].
## Clinical Characteristics
### Clinical Description
To date, approximately 150 individuals with a clinical diagnosis of Cantú syndrome have been identified; a pathogenic variant in ABCC9 or KCNJ8 has been identified in 107 individuals [Grange et al 2019]. The following description of the phenotypic features associated with this condition is based on this report.
### Table 2.
Cantú Syndrome: Frequency of Select Features
View in own window
Feature% of Persons
w/FeatureComment
Polyhydramnios57%
Prematurity (<37 weeks)58%
Neonatal hypertrichosis99%
Macrosomia38%Birth weight >4,000 g
Generalized edema at birth43%
Macrocephaly48% of adults
studied
Skeletal abnormalities19%Usually asymptomatic so detection dependent on imaging; not all persons had full skeletal survey
Gastroesophageal reflux42%
Cardiovascular findingsPDA58%
Valvular defects18%Bicuspid aortic valve, mitral valve regurgitation, aortic valve stenosis
Cardiac enlargement64%
Dilated aortic root32%
Pericardial effusion25%
Tortuous vascularity100% (10/10) on neurovascular imagingTrue number is unknown in entire population; neuroimaging at Washington University in St Louis showed that all tested persons have this finding in head & neck.
Pulmonary hypertension24%Seen in infancy; typically resolves w/age
Peripheral edema51%Usually develops in teenagers & young adults
Developmental delays63%Present in infants & young children related to hypotonia, but improve over time; most have normal intellect.
Hypotonia65%
Headaches40%Often migraine-type headache w/assoc symptoms
Seizures24%Various types
Behavioral issues 1ADHD19%
ASD16%
OCD13%
Anxiety13%
Depression19%
ADHD = attention-deficit/hyperactivity disorder; ASD = autism spectrum disorder; OCD = obsessive-compulsive disorder; PDA = patent ductus arteriosus
1\.
Self-reported in many individuals
Prenatal. Many pregnancies with a fetus with Cantú syndrome are complicated by polyhydramnios, leading in some instances to repeated amniotic fluid reductions as well as preterm labor and delivery.
Newborns. All newborns with Cantú syndrome have hypertrichosis with thick scalp hair and excessive hair growth on the forehead, face, back, and extremities. Some have thick and/or curly eyelashes. The hypertrichosis usually persists over time.
Many newborns have macrosomia (large birth weight and birth length) and macrocephaly.
Generalized edema at birth (observed on occasion) usually resolves spontaneously.
Growth. Ultimate adult height is usually within the normal range; however, short stature has been seen in a few individuals.
Macrocephaly, often present at birth, typically persists throughout life. Some individuals who do not have macrocephaly at birth have developed progressive macrocephaly in childhood.
Skeletal abnormalities are usually asymptomatic and identified on radiographs. Characteristic skeletal abnormalities have included thickening of the calvaria, broad ribs, platyspondyly, ovoid vertebral bodies, scoliosis, narrow thorax and shoulders, pectus carinatum, hypoplastic ischium and pubic bones, Erlenmeyer-flask-like long bones with metaphyseal flaring, narrow obturator foramen, and coxa vara.
Gastroesophageal reflux is reported by just under half of individuals. A smaller percentage report intestinal dysfunction characterized by chronic constipation or slow intestinal motility.
Cardiac findings include the following:
* Cardiac enlargement, with increased ventricular mass but normal chamber wall thickness and enlarged chambers of the heart, often present at birth. Despite the enlarged cardiac chambers, cardiac function is typically normal and ventricular contractility is increased on imaging studies [Grange et al 2006, Grange et al 2019]. Some patients note exercise intolerance, but others have been able to participate in organized sports without difficulty.
* Patent ductus arteriosus (PDA) in 58% (and described as extremely large in some), often requiring surgical closure in infancy or early childhood
* Bicuspid aortic valve with and without stenosis
* Pericardial effusion in about 25% of affected individuals. Small pericardial effusions may be asymptomatic; large fluid accumulations result in symptoms such as exercise intolerance and require intervention.
* Dilated aortic root and ascending aorta are present in about two thirds of individuals. The natural history is poorly understood. However, development of an aortic aneurysm is rare. Aortic aneurysm requiring surgical intervention was reported in one individual with an ABCC9 pathogenic variant [Hiraki et al 2014].
Tortuous vascularity including tortuous retinal vessels and multiple tortuous pulmonary arteriovenous communications have been reported [Scurr et al 2011, Grange et al 2019]. Abnormal tortuous vasculature in the brain is present in essentially all individuals who have been imaged specifically [Leon Guerrero et al 2016, Grange et al 2019].
Pulmonary hypertension has been reported in infants and young children, although the natural history is not well understood [Cantú et al 1982, Robertson et al 1999, Lazalde et al 2000, Kobayashi et al 2010, Scurr et al 2011]. In one child, pulmonary hypertension secondary to partial pulmonary venous obstruction was associated with severe mitral valve regurgitation that spontaneously resolved by age eight years [Kobayashi et al 2010]. In another individual, progressive (and ultimately fatal) pulmonary hypertension was reported [Park et al 2014]. In the majority of cases, pulmonary hypertension is mild and improves with age [Grange et al 2019].
Generalized edema, which may be present at birth, spontaneously resolves. Subsequently, edema involving the lower extremities and occasionally the arms and hands may develop over time, usually in adolescence or early adulthood. Puffiness of the eyelids is often observed. In one individual, lymphangiography demonstrated dilated lymphatic vessels in the legs with delayed lymphatic drainage [García-Cruz et al 2011]. In contrast, lymphatic studies were normal in another individual [Scurr et al 2011]. Therefore, it is unclear at this time whether the observed swelling is edema or lymphedema.
Intellect. Although the majority of affected individuals have normal intellect, mild learning disabilities and/or developmental delays have been observed, including delay in acquisition of early motor milestones (most likely related to decreased muscle tone) and delay in speech development. Ultimately, most affected individuals attend regular schools, and some are described as having a high IQ [Scurr et al 2011, Grange et al 2019].
Seizures are reported in about one quarter of individuals. Febrile, tonic-clonic, and absence seizure types have been observed as well as temporal lobe epilepsy.
Headaches are reported by many individuals, especially migraine-type headaches with associated aura, photophobia, and phonophobia, and occasionally with transient hemiparesis.
Behavioral problems have been reported in some individuals, including anxiety, mood swings, obsessive-compulsive disorder, and tics [Scurr et al 2011, Grange et al 2019]. Attention-deficit/hyperactivity disorder, autism spectrum disorder, and depression may also be present. Many individuals have self-reported these issues.
Features of a connective tissue abnormality are observed in many individuals with Cantú syndrome, including wrinkled or loose skin especially at birth, deep palmar and plantar creases, and joint hyperextensibility. Some have decreased subcutaneous fat with the appearance of a muscular build in childhood.
Less frequent features
* Umbilical hernia
* Pyloric stenosis
* Poor intestinal motility [Grange et al 2019]
* Ptosis
* Craniosynostosis involving the sagittal and coronal sutures in one individual [Hiraki et al 2014]
* Increased frequency of infections, raising the possibility of immune dysfunction [Scurr et al 2011, Grange et al 2019]
* Growth hormone deficiency in a few individuals [Cooper et al 2014, Grange et al 2019]
* Panhypopituitarism [Grange et al 2019, Theis et al 2019] and pituitary adenoma [Marques et al 2018] in a few individuals
The three individuals reported thus far with a pathogenic variant in KCNJ8 had typical clinical features seen in Cantú syndrome [Brownstein et al 2013, Cooper et al 2014, Chihara et al 2020]. The individual reported by Brownstein et al [2013] had the following additional abnormalities:
* Brain MRI: cerebral atrophy and thin corpus callosum
* Multiple tortuous venous collaterals and lack of flow in the inferior sagittal sinus
* Systemic vasculature: dilated hepatic and celiac arteries, dilated and tortuous intrahepatic arteries and veins
### Genotype-Phenotype Correlations
Current information about genotype-phenotype correlation in Cantú syndrome is limited.
No significant genotype-phenotype correlations for ABCC9 or KCNJ8 have been identified.
### Penetrance
Penetrance for Cantú syndrome in familial cases reported thus far appears to be complete although with variable expression [Grange et al 2019]. In a few families, somatic mosaicism for an ABCC9 variant has been identified in one of the parents, resulting in much milder phenotypic manifestations [Grange et al 2019; DK Grange, unpublished].
### Nomenclature
Cantú syndrome may also be referred to as hypertrichotic osteochondrodysplasia.
### Prevalence
The prevalence of Cantú syndrome is unknown. To date, about 150 individuals have been reported with Cantú syndrome. Two previously reported conditions, acromegaloid facial appearance (AFA) syndrome and hypertrichosis with acromegaloid facial features (HAFF) syndrome, are now realized to be cases of Cantú syndrome with variable and sometimes milder phenotypic features. Cantú syndrome has been reported worldwide and in all ethnic groups.
## Differential Diagnosis
### Table 4.
Genes of Interest in the Differential Diagnosis of Cantú Syndrome
View in own window
Gene(s) / Genetic MechanismDisorderMOIFeatures of This Disorder
Overlapping w/Cantú SyndromeDistinguishing from Cantú Syndrome
Abnormal methylation at 11p15.5
CDKN1C 1Beckwith-Wiedemann syndromeVariable 2Neonatal macrosomia; coarse facial features w/macroglossia; umbilical herniaNeonatal hypoglycemia, & hyperinsulinism; ear pits & creases; omphalocele; hemihypertrophy; abdominal tumors in childhood (Wilms tumor, hepatoblastoma)
ATP6V1B2
KCNH1
KCNN3Zimmermann-Laband syndrome (OMIM PS135500)ADHypertrichosis; coarse facial features; full lips; macrosomia at birth; PDA; aortic root dilatation; scoliosis; hypotoniaGingival hyperplasia or fibromatosis; bulbous nose; distal phalangeal hypoplasia; hypo/aplastic nails; hepatosplenomegaly; seizures; severe ID/DD in some persons
AGPAT2
BSCL2Berardinelli-Seip congenital lipodystrophyARMuscular build w/↓ subcutaneous fat in assoc w/cardiomegalyInsulin resistance; diabetes mellitus; hepatomegaly & hepatic steatosis; hypertrophy of skeletal muscles; hypertrophic cardiomyopathy different from cardiac involvement in Cantú syndrome
ANKRD1
BAG3
LMNA
MYBPC3
MYH6
MYH7
SCN5A
TNNT2
TTN
(~30 genes) 3Dilated cardiomyopathyADCardiomegalyAbsence of noncardiac findings
(Note: Persons w/Cantú syndrome have normal ventricular wall thickness & normal or enhanced myocardial function [despite enlargement of cardiac chambers] & high cardiac output.)
MYBPC3
MYH7
TNNI3
TNNT2
(~30 genes) 4Hypertrophic cardiomyopathyAD
KCNK4FHEIG syndrome (Bauer-Tartaglia syndrome) (OMIM 618381)ADHypertrichosis; coarse facial features; thick scalp hair; large mouth; hypotoniaOcular abnormalities (e.g. nystagmus & optic nerve hypoplasia); severe gingival hyperplasia; brachydactyly; ID/DD; epilepsy; lack of cardiac manifestations
GALNSMPS IVA (Morquio syndrome type A)ARCoarse facial features & hirsutism; some skeletal radiologic features (e.g., thickening of ribs)Flexion contractures; progressively worsening skeletal changes over time; progressive ID & neurologic deterioration in some persons; hepatomegaly & splenomegaly
GNPTABMucolipidosis III α/β (See GNPTAB Disorders.)AR
GNPTGMucolipidosis III gammaAR
IDSMPS II (Hunter syndrome)XL
IDUASevere MPS IAR
MAN2B1Alpha-mannosidosisAR
AD = autosomal dominant; AR = autosomal recessive; DD = developmental delay; FHEIG syndrome = facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth syndrome; ID = intellectual disability; MOI = mode of inheritance; MPS = mucopolysaccharidosis; PDA = patent ductus arteriosus; XL = X-linked
1\.
Beckwith-Wiedemann syndrome (BWS) is caused by an epigenetic or genomic alteration leading to abnormal methylation at 11p15.5 or a heterozygous BWS-causing pathogenic variant in CDKN1C.
2\.
The risk to the sibs of a child with BWS depends on the genetic basis for BWS in the proband.
3\.
Pathogenic variants in ANKRD1, BAG3, LMNA, MYBPC3, MYH6, MYH7, SCN5A, TNNT2, and TTN account for about one third of nonsyndromic dilated cardiomyopathy (DCM); about 30 genes are known to be associated with nonsyndromic DCM (see Dilated Cardiomyopathy Overview).
4\.
Pathogenic variants in MYBPC3, MYH7, TNNI3, and TNNT2 account for more than 90% of nonsyndromic hypertrophic cardiomyopathy (HCM); about 30 genes are known to be associated with nonsyndromic HCM (see Hypertrophic Cardiomyopathy Overview).
### Other Conditions
Congenital hypothyroidism. The macroglossia and hirsutism that can be seen in congenital hypothyroidism may overlap with features of Cantú syndrome.
Acromegaly. The macrocephaly, coarse facial features, and tall stature in some adults with Cantú syndrome have been confused with acromegaly due to excess human growth hormone.
Minoxidil treatment may lead to coarsening of facial features and hirsutism that has been called "pseudoacromegaly" [Ohko et al 2020]. Minoxidil has long been associated with hair growth and is used topically to treat scalp hair loss. When taken orally, it may cause generalized hirsutism, progressive coarsening of the facial features, and pericardial effusions, all of which can resemble the clinical features of Cantú syndrome.
Diazoxide treatment for hyperinsulinism may lead to hypertrichosis especially on the forehead, back, arms and legs, edema, and rarely pericardial effusion or pulmonary hypertension, which can resemble clinical features of Cantú syndrome [Herrera et al 2018].
Note: Both minoxidil and diazoxide can activate the same ATP-sensitive potassium (KATP) channels that are overactive in Cantú syndrome due to pathogenic variants in ABCC9 or KCNJ8.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with Cantú syndrome, the evaluations summarized in Table 5 (if not performed as part of the evaluation that led to the diagnosis) are recommended.
### Table 5.
Recommended Evaluations Following Initial Diagnosis in Individuals with Cantú Syndrome
View in own window
System/ConcernEvaluationComment
CardiacCardiology assessment to incl echocardiogram & electrocardiogram
Brain imagingBrain MRI w/MRA & MRVShould be considered for all persons, but esp if history of headaches, migraine headaches, or hemiparesis
Skeletal
* Radiographic skeletal survey to assess for bone abnormalities
* Eval for scoliosis
DevelopmentDevelopmental eval for infants & young children
Neuropsychological eval for older personsEspecially for those w/concern for ASD, ADHD, OCD, or depression
Genetic
counselingBy genetics professionals 1To inform affected persons & their families re nature, MOI, & implications of Cantú syndrome to facilitate medical & personal decision making
Family support/
resourcesAssess:
* Use of community or online resources such as Parent to Parent;
* Need for social work involvement for parental support.
ADHD = attention-deficit/hyperactivity disorder; ASD = autism spectrum disorder; MOI = mode of inheritance; MRA = magnetic resonance angiogram; MRV = magnetic resonance venography; OCD = obsessive-compulsive disorder
1\.
Medical geneticist, certified genetic counselor, or certified advanced genetic nurse
### Treatment of Manifestations
### Table 6.
Treatment of Manifestations in Individuals with Cantú Syndrome
View in own window
Manifestation/ConcernTreatmentConsiderations/Other
Cardiac issuesPDA, if present, often requires surgical or device closure in infancy or early childhood.
Pericardial effusion, if present, sometimes requires pericardiocentesis.Pericardial stripping may be required to prevent recurrent & hemodynamically significant pericardial effusion.
Peripheral edemaCompression stockings & other standard mgmt
HypertrichosisReferral to dermatologist for treatment optionsPossible treatments: shaving & (in teenagers & adults) use of depilatories or laser hair removal
ScoliosisBracing or surgical correction
Migraines or other
types of headachesReferral to neurologist for consideration of medication
Developmental delaySee Developmental Delay Management Issues.
PDA = patent ductus arteriosus
#### Developmental Delay Management Issues
The following information represents typical management recommendations for individuals with developmental delay in the United States; standard recommendations may vary from country to country.
Ages 0-3 years. Referral to an early intervention program is recommended for access to occupational, physical, speech, and feeding therapy as well as infant mental health services, special educators, and sensory impairment specialists. In the US, early intervention is a federally funded program available in all states that provides in-home services to target individual therapy needs.
Ages 3-5 years. In the US, developmental preschool through the local public school district is recommended. Before placement, an evaluation is made to determine needed services and therapies and an individualized education plan is developed for those who qualify based on established motor, language, social, or cognitive delay. The early intervention program typically assists with this transition.
All ages. Consultation with a developmental pediatrician is recommended to ensure the involvement of appropriate community, state, and educational agencies (US) and to support parents in maximizing quality of life.
#### Motor Delay
Gross motor delay. Physical therapy may be recommended if there are gross motor delays in infancy or early childhood due to hypotonia.
Fine motor delay. Occupational therapy is recommended for difficulty with fine motor skills that affect adaptive function such as feeding, grooming, dressing, and writing.
Oral motor dysfunction should be assessed in infants and clinical feeding evaluations and/or radiographic swallowing studies should be obtained for choking/gagging during feeds, poor weight gain, frequent respiratory illnesses, or feeding refusal that is not otherwise explained. Assuming that the child is safe to eat by mouth, feeding therapy (typically from an occupational or speech therapist) may be needed to help improve coordination or sensory-related feeding issues. Feeds can be thickened or chilled for safety. When feeding dysfunction is severe, an NG-tube or G-tube may be necessary.
#### Social/Behavioral Concerns
Children may qualify for and benefit from interventions used in treatment of autism spectrum disorder, including applied behavior analysis (ABA). ABA therapy is targeted to the individual child's behavioral, social, and adaptive strengths and weaknesses and typically performed one on one with a board-certified behavior analyst.
Consultation with a developmental pediatrician may be helpful in guiding parents through appropriate behavior management strategies or providing prescription medications, such as medication used to treat attention-deficit/hyperactivity disorder, when necessary.
### Surveillance
### Table 7.
Recommended Surveillance for Individuals with Cantú Syndrome
View in own window
System/ConcernEvaluationFrequency
Cardiac issues
* Echocardiogram & EKG to monitor cardiac size & function & for evidence of pericardial effusion starting in infancy
* Clinical eval & cardiac biomarkers such as BNP to monitor late development of high-output cardiac failure
Per cardiologist or annually
Peripheral
edemaMonitor w/history & examAnnually starting in adolescence
Cerebral
vasculature
abnormalityBrain MRI w/MRA & MRVIf persistent headaches or other neurologic symptoms develop
Headaches/
MigrainesEval by neurologistPer neurologist
Scoliosis
* Spine radiographs
* Orthopedic eval if scoliosis is present
If concern based on physical exam
BNP = brain natriuretic peptide; EKG = electrocardiogram; MRA = magnetic resonance angiogram; MRV = magnetic resonance venography
### Agents/Circumstances to Avoid
Avoid the following:
* Minoxidil
* Diazoxide
* Angiotensin-converting enzyme inhibitors
### Evaluation of Relatives at Risk
It is appropriate to clarify the genetic/clinical status of older and younger relatives of an affected individual in order to identify as early as possible those who should be evaluated and monitored for cardiac manifestations of Cantú syndrome, as well as peripheral edema and scoliosis (see Evaluations Following Initial Diagnosis and Surveillance).
Evaluations can include:
* Molecular genetic testing if the causative pathogenic variant in the family is known;
* Complete physical examination to assess for the characteristic clinical features, as well as an echocardiogram, electrocardiogram, and skeletal survey, should be performed if the pathogenic variant in the family is not known. Additional studies such as brain MRI with magnetic resonance angiogram and magnetic resonance venography may be indicated.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
Women affected by Cantú syndrome should be referred to a maternal-fetal medicine specialist for evaluation and management.
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Cantú Syndrome
|
c0795905
| 7,342 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK246980/
| 2021-01-18T21:36:34 |
{"mesh": ["C535572"], "synonyms": []}
|
A rare pituitary tumor characterized by the presence of a pituitary adenoma that has metastasized either within the central nervous system, or to distant sites. The vast majority of pituitary carcinomas are hormonally active, most frequently with ACTH or prolactin production. The most common clinical symptoms are diabetes insipidus, optic nerve dysfunction, anterior pituitary dysfunction, palsy of cranial nerves III, IV, or VI, and headaches, although patients may also be asymptomatic. The tumors behave aggressively, and prognosis is poor.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Pituitary carcinoma
|
c0346300
| 7,343 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=300385
| 2021-01-23T17:07:28 |
{"gard": ["9371"], "mesh": ["D010911"], "umls": ["C0346300"], "icd-10": ["C75.1"]}
|
A number sign (#) is used with this entry because antigens of the Diego blood group system result from variation in the SLC4A1 gene (109270) on chromosome 17q21.
Description
The Diego blood group system consists of 2 pairs of antithetical antigens, Di(a) and Di(b) and Wr(a) and Wr(b), and at least 17 low-frequency antigens that result from amino acid substitutions in SLC4A1, which encodes the erythrocyte band-3 protein. The low-frequency Di(a) and high-frequency Di(b) antigens represent leu854 and pro854, respectively. The low-frequency Wr(a) and high-frequency Wr(b) antigens represent lys658 and glu658, respectively. No healthy person with a Diego-null phenotype has been reported, reflecting the functional importance of SLC4A1 (summary by Daniel, 2002).
Clinical Features
The Di(a) antigen was first described in Venezuela on the basis of an antibody that had been the cause of hemolytic disease of the newborn (Levine et al., 1956). A second example of anti-Di(a) was found in Buffalo in the serum of a Polish mother, whose child also suffered from hemolytic disease of the newborn (Tatarsky et al., 1959). The Diego system shows polymorphism mainly in Mongolian peoples, e.g., Chinese and American Indians. In a family of Polish origin, Kusnierz-Alejska and Bochenek (1992) found anti-Di(a) antibody in the serum of a mother who gave birth to a newborn with severe hemolytic anemia. They identified the Di(a) antigen in 45 of 9,661 donor blood samples from different regions of Poland (0.46%). All 45 were of Polish ancestry.
Mapping
Zelinski et al. (1993) showed that the DI blood group is tightly linked to the erythrocyte surface protein band-3 locus (SLC4A1); maximum lod = 5.42 at theta = 0.00. Looser linkage between DI and D17S41 (maximum lod = 3.14 at theta = 0.09) for combined paternal and maternal meioses was also established. The EPB3 gene is located at 17q21-q22.
Molecular Genetics
Bruce et al. (1994) demonstrated that the Di(a)/Di(b) polymorphism is a single amino acid substitution at position 854 of the band-3 protein, with proline of the wildtype band-3 protein corresponding to the Di(b) antigen and leucine to the Di(a) antigen (109270.0017).
Data on gene frequencies of allelic variants were tabulated by Roychoudhury and Nei (1988).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
BLOOD GROUP, DIEGO SYSTEM
|
None
| 7,344 |
omim
|
https://www.omim.org/entry/110500
| 2019-09-22T16:44:21 |
{"omim": ["110500"], "synonyms": ["Alternative titles", "DIEGO BLOOD GROUP SYSTEM"]}
|
Paraneoplastic neurologic disorders are a group of rare degenerative conditions that are triggered by a person's immune system response to a cancerous tumor. Researchers believe these disorders occur when cancer-fighting antibodies or white blood cells known as T cells mistakenly attack normal cells in the nervous system. Paraneoplastic neurologic disorders typically develop after mid-adulthood and are most common in people with lung, ovarian, lymphatic, or breast cancer. Symptoms generally develop over a period of days to weeks and usually occur prior to tumor detection. These symptoms may include difficulty in walking and/or swallowing, loss of muscle tone, loss of fine motor coordination, slurred speech, memory loss, vision problems, sleep disturbances, dementia, seizures, sensory loss in the limbs, and vertigo. Paraneoplastic neurologic disorders include Lambert-Eaton myasthenic syndrome, stiff-person syndrome, encephalomyelitis (inflammation of the brain and spinal cord), myasthenia gravis, cerebellar degeneration, limbic and/or brainstem encephalitis, neuromyotonia, and opsoclonus (involving eye movement) and sensory neuropathy. Treatment involves treatment of the underlying tumor, immunotherapy, and supportive therapy.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Paraneoplastic Neurologic Disorders
|
c1956415
| 7,345 |
gard
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https://rarediseases.info.nih.gov/diseases/9415/paraneoplastic-neurologic-disorders
| 2021-01-18T17:58:26 |
{"mesh": ["D004418"], "synonyms": ["PND"]}
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Tumors of the hematopoietic and lymphoid tissues
Micrograph of a plasmacytoma, a hematological malignancy
Tumors of the hematopoietic and lymphoid tissues (American English) or tumours of the haematopoietic and lymphoid malignancies (British English) are tumors that affect the blood, bone marrow, lymph, and lymphatic system.[1][2] Because these tissues are all intimately connected through both the circulatory system and the immune system, a disease affecting one will often affect the others as well, making myeloproliferation and lymphoproliferation (and thus the leukemias and the lymphomas) closely related and often overlapping problems.
While uncommon in solid tumors, chromosomal translocations are a common cause of these diseases. This commonly leads to a different approach in diagnosis and treatment of haematological malignancies.
Haematological malignancies are malignant neoplasms ("cancer"), and they are generally treated by specialists in hematology and/or oncology. In some centers "haematology/oncology" is a single subspecialty of internal medicine while in others they are considered separate divisions (there are also surgical and radiation oncologists). Not all haematological disorders are malignant ("cancerous"); these other blood conditions may also be managed by a hematologist.
Hematological malignancies may derive from either of the two major blood cell lineages: myeloid and lymphoid cell lines. The myeloid cell line normally produces granulocytes, erythrocytes, thrombocytes, macrophages and mast cells; the lymphoid cell line produces B, T, NK and plasma cells. Lymphomas, lymphocytic leukemias, and myeloma are from the lymphoid line, while acute and chronic myelogenous leukemia, myelodysplastic syndromes and myeloproliferative diseases are myeloid in origin.
A subgroup of them are more severe and are known as haematological malignancies (British English)/hematological malignancies (American English) or blood cancer. They may also be referred to as liquid tumors.[3][4]
## Contents
* 1 Diagnosis
* 1.1 Classification
* 1.1.1 Classification according to WHO
* 2 Treatment
* 2.1 Follow-up
* 3 Epidemiology
* 4 See also
* 5 References
* 6 External links
## Diagnosis[edit]
For the analysis of a suspected hematological malignancy, a complete blood count and blood film are essential, as malignant cells can show in characteristic ways on light microscopy. When there is lymphadenopathy, a biopsy from a lymph node is generally undertaken surgically. In general, a bone marrow biopsy is part of the "work up" for the analysis of these diseases. All specimens are examined microscopically to determine the nature of the malignancy. A number of these diseases can now be classified by cytogenetics (AML, CML) or immunophenotyping (lymphoma, myeloma, CLL) of the malignant cells.
### Classification[edit]
Historically, hematological malignancies have been most commonly divided by whether the malignancy is mainly located in the blood (leukemia) or in lymph nodes (lymphomas). However, the influential WHO Classification (published in 2001 and updated in 2008 and 2016) places a greater emphasis on cell lineage.[citation needed]
Relative proportions of hematological malignancies in the United States[5]
Type of hematological malignancy Percentage Total
Leukemias — 30.4%
Acute lymphoblastic leukemia (ALL) 4.0%
Acute myelogenous leukemia (AML) 8.7%
Chronic lymphocytic leukemia (CLL)
sorted under lymphomas according to current WHO classification; called small lymphocytic lymphoma (SLL) when leukemic cells are absent. 10.2%
Chronic myelogenous leukemia (CML) 3.7%
Acute monocytic leukemia (AMoL) 0.7%
Other leukemias 3.1%
Lymphomas — 55.6%
Hodgkin's lymphomas (all four subtypes) 7.0%
Non-Hodgkin's lymphomas (all subtypes) 48.6%
Myelomas 14.0%
Total 100%
#### Classification according to WHO[edit]
4th Edition[6]
NOS = "Not otherwise specified"
* Myeloid neoplasms
* Myeloproliferative neoplasms
* Chronic myeloid leukaemia, BCR-ABL1-positive
* Chronic neutrophilic leukaemia
* Polycythaemia vera
* Primary myelofibrosis
* Essential thrombocythaemia
* Chronic eosinophilic leukaemia, NOS
* Myeloproliferative neoplasm, unclassifiable
* Mastocytosis
* Cutaneous mastocytosis
* Indolent systemic mastocytosis
* Systemic mastocytosis with an associated haematological neoplasm
* Aggressive systemic mastocytosis
* Mast cell leukaemia
* Mast cell sarcoma
* Myeloid/lymphoid neoplasms with eosinophilia and gene rearrangement
* Myeloid/lymphoid neoplasms with PDGFRA rearrangement
* Myeloid/lymphoid neoplasms with PDGFRB rearrangement
* Myeloid/lymphoid neoplasms with FGFR1 rearrangement
* Myeloid/lymphoid neoplasms with PCM1―JAK2
* Myelodysplastic/myeloproliferative neoplasms
* Chronic myelomonocytic leukaemia
* Atypical chronic myeloid leukaemia, BCR-ABL1―negative
* Juvenile myelomonocytic leukaemia
* Myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis
* Myelodysplastic/myeloproliferative neoplasm, unclassifiable
* Myelodysplastic syndromes
* Myelodysplastic syndrome with single lineage dysplasia
* Myelodysplastic syndrome with ring sideroblasts and single lineage dysplasia
* Myelodysplastic syndrome with ring sideroblasts and multilineage dysplasia
* Myelodysplastic syndrome with multilineage dysplasia
* Myelodysplastic syndrome with excess blasts
* Myelodysplastic syndrome with isolated del(5q)
* Myelodysplastic syndrome, unclassifiable
* Refractory cytopenia of childhood
* Myeloid neoplasms with germline predisposition
* Acute myeloid leukaemia with germline CEBPA mutation
* Myeloid neoplasms with germline DDX41 mutation
* Myeloid neoplasms with germline RUNX1 mutation
* Myeloid neoplasms with germline ANKRD26 mutation
* Myeloid neoplasms with germline ETV6 mutation
* Myeloid neoplasms with germline GATA2 mutation
* Acute myeloid leukaemia (AML) and related precursor neoplasms
* AML with recurrent genetic abnormalities
* AML with t(8;21)(q22;q22.1); RUNX1-RUNX1T1
* AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11
* Acute promyelocytic leukaemia with PML-RARA
* AML with t(9;11)(p21.3;q23.3); KMT2A-MLLT3
* AML with t(6;9)(p23;q34.1); DEK-NUP214
* AML with inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2, MECOM
* AML (megakaryoblastic) with t(1;22)(p13.3;q13.1); RBM15-MKL1
* AML with BCR-ABL1
* AML with mutated NPM1
* AML with biallelic mutation of CEBPA
* AML with mutated RUNX1
* AML with myelodysplasia-related changes
* Therapy-related myeloid neoplasms
* Acute myeloid leukaemia, NOS
* AML with minimal differentiation
* AML without maturation
* AML with maturation
* Acute myelomonocytic leukaemia
* Acute monoblastic and monocytic leukaemia
* Pure erythroid leukaemia
* Acute megakaryoblastic leukaemia
* Acute basophilic leukaemia
* Acute panmyelosis with myelofibrosis
* Myeloid sarcoma
* Myeloid proliferations associated with Down syndrome
* Transient abnormal myelopoiesis associated with Down syndrome
* Myeloid leukaemia associated with Down syndrome
* Blastic plasmacytoid dendritic cell neoplasm
* Acute leukaemias of ambiguous lineage
* Acute undifferentiated leukaemia
* Mixed-phenotype acute leukaemia with t(9;22)(q34.1;q11.2); BCR-ABL1
* Mixed-phenotype acute leukaemia with t(v;11q23.3); KMT2A-rearranged
* Mixed-phenotype acute leukaemia, B/myeloid, NOS
* Mixed-phenotype acute leukaemia, T/myeloid, NOS
* Mixed-phenotype acute leukaemia, NOS, rare types
* Acute leukaemias of ambiguous lineage, NOS
* Lymphoid neoplasms
* Precursor lymphoid neoplasms
* B-lymphoblastic leukaemia/lymphoma, NOS
* B-lymphoblastic leukaemia/lymphoma with t(9;22)(q34.1;q11.2); BCR-ABL1
* B-lymphoblastic leukaemia/lymphoma with t(v;11q23.3); KMT2A-rearranged
* B-lymphoblastic leukaemia/lymphoma with t(12;21)(p13.2;q22.1); ETV6-RUNX1
* B-lymphoblastic leukaemia/lymphoma with hyperdiploidy
* B-lymphoblastic leukaemia/lymphoma with hypodiploidy (hypodiploid ALL)
* B-lymphoblastic leukaemia/lymphoma with t(5;14)(q31.1;q32.1); IGH/IL3
* B-lymphoblastic leukaemia/lymphoma with t(1;19)(q23;p13.3); TCF3-PBX1
* B-lymphoblastic leukaemia/lymphoma, BCR-ABL 1―like
* B-lymphoblastic leukaemia/lymphoma with iAMP21
* T-lymphoblastic leukaemia/lymphoma
* Early T-cell precursor lymphoblastic leukaemia
* NK-lymphoblastic leukaemia/lymphoma
* Mature B-cell neoplasms
* Chronic lymphocytic leukaemia (CLL)/ small lymphocytic lymphoma
* Monoclonal B-cell lymphocytosis, CLL-type
* Monoclonal B-cell lymphocytosis, non-CLL-type
* B-cell prolymphocytic leukaemia
* Splenic marginal zone lymphoma
* Hairy cell leukaemia
* Splenic B-cell lymphoma/leukaemia, unclassifiable
* Splenic diffuse red pulp small B-cell lymphoma
* Hairy cell leukaemia variant
* Lymphoplasmacytic lymphoma
* Waldentrom macroglobulinemia
* IgM monoclonal gammopathy of undetermined significance
* Heavy chain diseases
* Mu heavy chain disease
* Gamma heavy chain disease
* Alpha heavy chain disease
* Plasma cell neoplasms
* Non-IgM monoclonal gammopathy of undetermined significance
* Plasma cell myeloma
* Solitary plasmacytoma of bone
* Extraosseous plasmacytoma
* Monoclonal immunoglobulin deposition diseases
* Primary amyloidosis
* Light chain and heavy chain deposition diseases
* Extranodal marginal zone lymphoma of mucosa- associated lymphoid tissue (MALT lymphoma)
* Nodal marginal zone lymphoma
* Paediatric nodal marginal zone lymphoma
* Follicular lymphoma
* In situ follicular neoplasia
* Duodenal-type follicular lymphoma
* Testicular follicular lymphoma
* Paediatric-type follicular lymphoma
* Large B-cell lymphoma with IRF4 rearrangement
* Primary cutaneous follicle centre lymphoma
* Mantle cell lymphoma
* In situ mantle cell neoplasia
* Diffuse large B-cell lymphoma (DLBCL), NOS
* Germinal centre B-cell subtype
* Activated B-cell subtype
* T-cell/histiocyte-rich large B-cell lymphoma
* Primary DLBCL of the CNS
* Primary cutaneous DLBCL, leg type
* EBV-positive DLBCL, NOS
* EBV-positive mucocutaneous ulcer
* DLBCL associated with chronic inflammation
* Fibrin-associated diffuse large B-cell lymphoma
* Lymphomatoid granulomatosis, grade 1,2
* Lymphomatoid granulomatosis, grade 3
* Primary mediastinal (thymic) large B-cell lymphoma
* Intravascular large B-cell lymphoma
* ALK-positive large B-cell lymphoma
* Plasmablastic lymphoma
* Primary effusion lymphoma
* Multicentric Castleman disease
* HHV8-positive DLBCL, NOS
* HHV8-positive germinotropic lymphoproliferative disorder
* Burkitt lymphoma
* Burkitt-like lymphoma with 11q aberration
* High-grade B-cell lymphoma
* High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements
* High-grade B-cell lymphoma, NOS
* B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic Hodgkin lymphoma
* Mature T- and NK-cell neoplasms
* T-cell prolymphocytic leukaemia
* T-cell large granular lymphocytic leukaemia
* Chronic lymphoproliferative disorder of NK cells
* Aggressive NK-cell leukaemia
* Systemic EBV-positive T-cell lymphoma of childhood
* Chronic active EBV infection of T- and NK-cell type, systemic form
* Hydroa vacciniforme-like lymphoproliferative disorder
* Severe mosquito bite allergy
* Adult T-cell leukaemia/lymphoma
* Extranodal NK/T-cell lymphoma, nasal type
* Enteropathy-associated T-cell lymphoma
* Monomorphic epitheliotropic intestinal T-cell lymphoma
* Intestinal T-cell lymphoma, NOS
* Indolent T-cell lymphoproliferative disorder of the gastrointestinal tract
* Hepatosplenic T-cell lymphoma
* Subcutaneous panniculitis-like T-cell lymphoma
* Mycosis fungoides
* Sezary syndrome
* Primary cutaneous CD30-positive T-cell lymphoproliferative disorders
* Lymphomatoid papulosis
* Primary cutaneous anaplastic large cell lymphoma
* Primary cutaneous gamma delta T-cell lymphoma
* Primary cutaneous CD8-positive aggressive epidermotropic cytotoxic T-cell lymphoma
* Primary cutaneous acral CD8-positive T-cell lymphoma
* Primary cutaneous CD4-positive small/medium T-cell lymphoproliferative disorder
* Peripheral T-cell lymphoma, NOS
* Angioimmunoblastic T-cell lymphoma
* Follicular T-cell lymphoma
* Nodal peripheral T-cell lymphoma with T follicular helper phenotype
* Anaplastic large cell lymphoma, ALK-positive
* Anaplastic large cell lymphoma, ALK-negative
* Breast implant-associated anaplastic large cell lymphoma
* Hodgkin lymphomas
* Nodular lymphocyte predominant Hodgkin lymphoma
* Classic Hodgkin lymphoma
* Nodular sclerosis classic Hodgkin lymphoma
* Lymphocyte-rich classic Hodgkin lymphoma
* Mixed cellularity classic Hodgkin lymphoma
* Lymphocyte-depleted classic Hodgkin lymphoma
* Immunodeficiency-associated lymphoproliferative disorders
* Post-transplant lymphoproliferative disorders (PTLD)
* Non-destructive PTLD
* Plasmacytic hyperplasia PTLD
* Infectious mononucleosis PTLD
* Florid follicular hyperplasia
* Polymorphic PTLD
* Monomorphic PTLD
* Classic Hodgkin Lymphoma PTLD
* Other iatrogenic immunodeficiency- associated lymphoproliferative disorders
* Histiocytic and dendritic cell neoplasms
* Histiocytic sarcoma
* Langerhans cell histiocytosis, NOS
* Langerhans cell histiocytosis, monostotic
* Langerhans cell histiocytosis, polystotic
* Langerhans cell histiocytosis, disseminated
* Langerhans cell sarcoma
* Indeterminate dendritic cell tumour
* Interdigitating dendritic cell sarcoma
* Follicular dendritic cell sarcoma
* Fibroblastic reticular cell tumour
* Disseminated juvenile xanthogranuloma
* Erdheim–Chester disease
## Treatment[edit]
Treatment can occasionally consist of "watchful waiting" (e.g. in CLL) or symptomatic treatment (e.g. blood transfusions in MDS). The more aggressive forms of disease require treatment with chemotherapy, radiotherapy, immunotherapy and—in some cases—a bone marrow transplant. The use of rituximab has been established for the treatment of B-cell–derived hematologic malignancies, including follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL).[7]
### Follow-up[edit]
If treatment has been successful ("complete" or "partial remission"), a person is generally followed up at regular intervals to detect recurrence and monitor for "secondary malignancy" (an uncommon side-effect of some chemotherapy and radiotherapy regimens—the appearance of another form of cancer). In the follow-up, which should be done at pre-determined regular intervals, general anamnesis is combined with complete blood count and determination of lactate dehydrogenase or thymidine kinase in serum. Haematological malignancies as well as their treatments are associated with complications affecting many organs, with the lungs being frequently affected [8][9]
## Epidemiology[edit]
Taken together, haematological malignancies account for 9.5% of new cancer diagnoses in the United States[10] and 30,000 patients in the UK are diagnosed each year.[11] Within this category, lymphomas are more common than leukemias.[citation needed]
## See also[edit]
* Myelodysplastic–myeloproliferative diseases
## References[edit]
1. ^ Vardiman, JW; Thiele, J; Arber, DA; Brunning, RD; Borowitz, MJ; Porwit, A; Harris, NL; Le Beau, MM; Hellström-Lindberg, E; Tefferi, A; Bloomfield, CD (30 July 2009). "The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes". Blood. 114 (5): 937–51. doi:10.1182/blood-2009-03-209262. PMID 19357394. S2CID 3101472.
2. ^ World Cancer Report 2014. World Health Organization. 2014. pp. Chapter 5.13. ISBN 978-9283204299.
3. ^ Juo, Pei-Show (2001). Concise Dictionary of Biomedicine and Molecular Biology (2nd ed.). Hoboken: CRC Press. p. 653. ISBN 9781420041309.
4. ^ Cancer Rehabilitation Medicine Quick Reference (RMQR). New York: Demos Medical Publishing. 2013. p. 26. ISBN 9781617050008.
5. ^ Horner MJ, Ries LAG, Krapcho M, Neyman N, et al. (eds). "SEER Cancer Statistics Review, 1975–2006". Surveillance Epidemiology and End Results (SEER). Bethesda, MD: National Cancer Institute. Retrieved 3 November 2009. "Table 1.4: Age-Adjusted SEER Incidence and U.S. Death Rates and 5-Year Relative Survival Rates By Primary Cancer Site, Sex and Time Period"CS1 maint: multiple names: authors list (link)
6. ^ al.], edited by Steven H. Swerdlow ... [et (2008). WHO classification of tumours of haematopoietic and lymphoid tissues (4th. ed.). Lyon, France: International Agency for Research on Cancer. p. 10. ISBN 978-9283224310.CS1 maint: extra text: authors list (link)
7. ^ "The Clinical and Economic Value of Rituximab for the Treatment of Hematologic Malignancies". Contemporary Oncology. Retrieved 14 September 2011.
8. ^ Br J Hosp Med (Lond). 2014 Dec;75(12):691-7. Non-infectious respiratory disease in non-HIV immunocompromised patients. Jose RJ1, Faiz SA, Dickey BF, Brown JS. doi: 10.12968/hmed.2014.75.12.691.
9. ^ Br J Hosp Med (Lond). 2014 Dec;75(12):685-90. Infectious respiratory disease in non-HIV immunocompromised patients. Jose RJ1, Dickey BF, Brown JS. PMID: 25488531 DOI: 10.12968/hmed.2014.75.12.685
10. ^ "Facts & Statistics". The Leukemia and Lymphoma Society. Archived from the original on 27 May 2010. Retrieved 3 November 2009.
11. ^ "Facts about blood cancers". Leukaemia & Lymphoma Research. Retrieved 24 September 2013.
## External links[edit]
Classification
D
* ICD-10: C81-C96
* ICD-9-CM: 200-209
* ICD-O: 9590-9999
* MeSH: D019337
* v
* t
* e
Leukaemias, lymphomas and related disease
B cell
(lymphoma,
leukemia)
(most CD19
* CD20)
By
development/
marker
TdT+
* ALL (Precursor B acute lymphoblastic leukemia/lymphoma)
CD5+
* naive B cell (CLL/SLL)
* mantle zone (Mantle cell)
CD22+
* Prolymphocytic
* CD11c+ (Hairy cell leukemia)
CD79a+
* germinal center/follicular B cell (Follicular
* Burkitt's
* GCB DLBCL
* Primary cutaneous follicle center lymphoma)
* marginal zone/marginal zone B-cell (Splenic marginal zone
* MALT
* Nodal marginal zone
* Primary cutaneous marginal zone lymphoma)
RS (CD15+, CD30+)
* Classic Hodgkin lymphoma (Nodular sclerosis)
* CD20+ (Nodular lymphocyte predominant Hodgkin lymphoma)
PCDs/PP
(CD38+/CD138+)
* see immunoproliferative immunoglobulin disorders
By infection
* KSHV (Primary effusion)
* EBV
* Lymphomatoid granulomatosis
* Post-transplant lymphoproliferative disorder
* Classic Hodgkin lymphoma
* Burkitt's lymphoma
* HCV
* Splenic marginal zone lymphoma
* HIV (AIDS-related lymphoma)
* Helicobacter pylori (MALT lymphoma)
Cutaneous
* Diffuse large B-cell lymphoma
* Intravascular large B-cell lymphoma
* Primary cutaneous marginal zone lymphoma
* Primary cutaneous immunocytoma
* Plasmacytoma
* Plasmacytosis
* Primary cutaneous follicle center lymphoma
T/NK
T cell
(lymphoma,
leukemia)
(most CD3
* CD4
* CD8)
By
development/
marker
* TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma)
* prolymphocyte (Prolymphocytic)
* CD30+ (Anaplastic large-cell lymphoma
* Lymphomatoid papulosis type A)
Cutaneous
MF+variants
* indolent: Mycosis fungoides
* Pagetoid reticulosis
* Granulomatous slack skin
aggressive: Sézary disease
* Adult T-cell leukemia/lymphoma
Non-MF
* CD30-: Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma
* Pleomorphic T-cell lymphoma
* Lymphomatoid papulosis type B
* CD30+: CD30+ cutaneous T-cell lymphoma
* Secondary cutaneous CD30+ large-cell lymphoma
* Lymphomatoid papulosis type A
Other
peripheral
* Hepatosplenic
* Angioimmunoblastic
* Enteropathy-associated T-cell lymphoma
* Peripheral T-cell lymphoma not otherwise specified (Lennert lymphoma)
* Subcutaneous T-cell lymphoma
By infection
* HTLV-1 (Adult T-cell leukemia/lymphoma)
NK cell/
(most CD56)
* Aggressive NK-cell leukemia
* Blastic NK cell lymphoma
T or NK
* EBV (Extranodal NK-T-cell lymphoma/Angiocentric lymphoma)
* Large granular lymphocytic leukemia
Lymphoid+
myeloid
* Acute biphenotypic leukaemia
Lymphocytosis
* Lymphoproliferative disorders (X-linked lymphoproliferative disease
* Autoimmune lymphoproliferative syndrome)
* Leukemoid reaction
* Diffuse infiltrative lymphocytosis syndrome
Cutaneous lymphoid hyperplasia
* Cutaneous lymphoid hyperplasia
* with bandlike and perivascular patterns
* with nodular pattern
* Jessner lymphocytic infiltrate of the skin
General
* Hematological malignancy
* leukemia
* Lymphoproliferative disorders
* Lymphoid leukemias
* v
* t
* e
Myeloid-related hematological malignancy
CFU-GM/
and other granulocytes
CFU-GM
Myelocyte
AML:
* Acute myeloblastic leukemia
* M0
* M1
* M2
* APL/M3
MP
* Chronic neutrophilic leukemia
Monocyte
AML
* AMoL/M5
* Myeloid dendritic cell leukemia
CML
* Philadelphia chromosome
* Accelerated phase chronic myelogenous leukemia
Myelomonocyte
AML
* M4
MD-MP
* Juvenile myelomonocytic leukemia
* Chronic myelomonocytic leukemia
Other
* Histiocytosis
CFU-Baso
AML
* Acute basophilic
CFU-Eos
AML
* Acute eosinophilic
MP
* Chronic eosinophilic leukemia/Hypereosinophilic syndrome
MEP
CFU-Meg
MP
* Essential thrombocytosis
* Acute megakaryoblastic leukemia
CFU-E
AML
* Erythroleukemia/M6
MP
* Polycythemia vera
MD
* Refractory anemia
* Refractory anemia with excess of blasts
* Chromosome 5q deletion syndrome
* Sideroblastic anemia
* Paroxysmal nocturnal hemoglobinuria
* Refractory cytopenia with multilineage dysplasia
CFU-Mast
Mastocytoma
* Mast cell leukemia
* Mast cell sarcoma
* Systemic mastocytosis
Mastocytosis:
* Diffuse cutaneous mastocytosis
* Erythrodermic mastocytosis
* Adult type of generalized eruption of cutaneous mastocytosis
* Urticaria pigmentosa
* Mast cell sarcoma
* Solitary mastocytoma
Systemic mastocytosis
* Xanthelasmoidal mastocytosis
Multiple/unknown
AML
* Acute panmyelosis with myelofibrosis
* Myeloid sarcoma
MP
* Myelofibrosis
* Acute biphenotypic leukaemia
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Tumors of the hematopoietic and lymphoid tissues
|
None
| 7,346 |
wikipedia
|
https://en.wikipedia.org/wiki/Tumors_of_the_hematopoietic_and_lymphoid_tissues
| 2021-01-18T19:08:25 |
{"orphanet": ["68347"], "synonyms": [], "wikidata": ["Q2509220"]}
|
A number sign (#) is used with this entry because of evidence that neurogenic arthrogryposis multiplex congenita with myelin defect (AMCNMY) is caused by homozygous or compound heterozygous mutation in the LGI4 gene (608303) on chromosome 19q13.
Description
AMCNMY is an autosomal recessive severe neurologic disorder with onset in utero. Most affected individuals die in utero or are subject to pregnancy termination because of lack of fetal movements and prenatal evidence of contractures of virtually all joints. Those who survive have generalized contractures and hypotonia. The disorder is caused by a neurogenic defect and poor or absent myelin formation around peripheral nerves rather than by a muscular defect (summary by Xue et al., 2017).
Clinical Features
Xue et al. (2017) reported 4 unrelated families in which a total of 9 offspring had AMC. There were 6 affected fetuses who either died in utero or showed fetal akinesia accompanied by abnormal prenatal ultrasound findings resulting in termination of the pregnancy, 2 liveborn infants who died in the neonatal period, and 1 living boy who was 6 years old. The pregnancies were characterized by hypo- or akinesia in utero. Prenatal imaging and postmortem examination showed distal arthrogryposis and fetal akinesia sequence with camptodactyly, adduction of thumbs, clubfeet, flexion of feet, knees, wrists, and elbows, and microretrognathia. Two patients had pulmonary hypoplasia. The only living patient, a 6-year-old boy, was born hypotonic with contractures and required artificial respiration until 4 months of age. He had poor head control, verbal developmental delay, and onset of seizures at age 1 year. Dysmorphic features included prominent ears, narrow forehead, high-arched palate, reduced mouth opening, dental crowding, esotropia, strabismus, and ptosis. Other findings included low muscle bulk, scapular winging with internal shoulder rotation, elbow hyperextension, pronation and ulnar deviation at wrists, hand contractures, overlapping fusiform fingers, and areflexia.
Inheritance
The transmission pattern of AMCNMY in the families reported by Xue et al. (2017) was consistent with autosomal recessive inheritance.
Molecular Genetics
In 9 offspring from 4 unrelated families with AMCNMY, Xue et al. (2017) identified homozygous or compound heterozygous mutations in the LGI4 gene (608303.0001-608303.0006). The mutations, which were found by exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the families. Immunolabeling and electron microscopy of sciatic nerve from 1 of the affected fetuses showed the presence of axons and Schwann cells, but there was a lack of myelinated fibers and absence of myelin basic protein (MBP; 159430). Studies of patient cells from 2 other families showed that the mutations caused a defect in LGI4 secretion, which was hypothesized to result in a defect in the crosstalk between Schwann cells and axons to initiate myelination. The findings indicated that the arthrogryposis in these patients was due to peripheral hypomyelination resulting from defective axoglial function.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Poor head control Face \- Retrognathia \- Micrognathia \- Narrow forehead Ears \- Prominent ears Eyes \- Esotropia \- Strabismus \- Ptosis Mouth \- High-arched palate \- Reduced mouth opening Teeth \- Dental crowding RESPIRATORY Lung \- Pulmonary hypoplasia (in some patients) CHEST Ribs Sternum Clavicles & Scapulae \- Internally rotated shoulders \- Scapular winging SKELETAL \- Arthrogryposis multiplex congenita \- Contractures \- Distal arthrogryposis Pelvis \- Hip contractures Limbs \- Knee contractures \- Elbow contractures \- Elbow hyperextension \- Wrist contractures \- Ankle contractures Hands \- Flexion of hands \- Camptodactyly Feet \- Flexion of feet \- Club feet MUSCLE, SOFT TISSUES \- Hypotonia \- Decreased muscle bulk NEUROLOGIC Central Nervous System \- Delayed verbal development (1 patient) \- Seizures (1 patient) Peripheral Nervous System \- Absence of myelin on peripheral nerves \- Areflexia PRENATAL MANIFESTATIONS Movement \- Fetal akinesia \- Decreased fetal movements MISCELLANEOUS \- Onset in utero \- Most patients die in utero or in the neonatal period MOLECULAR BASIS \- Caused by mutation in the leucine-rich gene, glioma-inactivated, 4 gene (LGI4, 608303.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
ARTHROGRYPOSIS MULTIPLEX CONGENITA, NEUROGENIC, WITH MYELIN DEFECT
|
c4479539
| 7,347 |
omim
|
https://www.omim.org/entry/617468
| 2019-09-22T15:45:47 |
{"omim": ["617468"], "orphanet": ["2680"], "synonyms": []}
|
Infantile apnea is a cessation of respiratory air flow that may affect newborns or older children because of neurological impairment of the respiratory rhythm or obstruction of air flow through the air passages. The symptoms include cyanosis, pallor or bradycardia and snoring in case of obstructive apnea.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Infantile apnea
|
c0745261
| 7,348 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=70590
| 2021-01-23T17:54:21 |
{"gard": ["6779"], "icd-10": ["P28.4"], "synonyms": ["Apnea of infancy"]}
|
Familial atrial fibrillation is an inherited heart condition that disrupts the heart's rhythm. It is characterized by erratic electrical activity in the heart's upper chambers (the atria), causing an irregular response in the heart's lower chambers (the ventricles). This causes a fast and irregular heartbeat (arrhythmia). Signs and symptoms may include dizziness, chest pain, palpitations, shortness of breath, or fainting. Affected people also have an increased risk of stroke and sudden death. While complications may occur at any age, some affected people never have associated health problems. Familial atrial fibrillation may be caused by changes (mutations) in any of various genes, some of which have not been identified. It is most often inherited in an autosomal dominant manner, but autosomal recessive inheritance has been reported.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Familial atrial fibrillation
|
c1843687
| 7,349 |
gard
|
https://rarediseases.info.nih.gov/diseases/9740/familial-atrial-fibrillation
| 2021-01-18T18:00:36 |
{"mesh": ["C538261"], "omim": ["608583"], "umls": ["C1843687"], "orphanet": ["334"], "synonyms": ["Atrial fibrillation autosomal dominant", "Autosomal dominant atrial fibrillation", "Atrial fibrillation, familial", "ATFB"]}
|
Linear scleroderma is one sub-type of localized scleroderma, most commonly occurring in childhood. It is characterized by abnormalities of the skin and subcutaneous tissues that often follow a dermatomal distribution and that are found on one side of the body. Besides the lesion in the face or scalp there are also abnormalities of the muscles, fat tissue and skull. When the face is affected, some strips located on the forehead may be hollow and lead to an appearance termed "en coup de sabre". In most cases, Raynaud's phenomenon is absent. The exact cause is still unknown but may be related to an autoimmune reaction resulting in too much collagen. Management is symptomatic and includes immunosupressant medication. Physical therapy is helpful for the muscle retraction problems.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Linear scleroderma
|
c0263409
| 7,350 |
gard
|
https://rarediseases.info.nih.gov/diseases/9513/linear-scleroderma
| 2021-01-18T17:59:22 |
{"mesh": ["D012594"], "umls": ["C0263409"], "synonyms": ["Scleroderma, linear", "En coup de sabre"]}
|
Traumatic anserine folliculosis
SpecialtyDermatology
Traumatic anserine folliculosis is a curious gooseflesh-like follicular hyperkeratosis that may result from persistent pressure and lateral friction of one skin surface against another.[1]:775
## See also[edit]
* List of cutaneous conditions
## References[edit]
1. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
This condition of the skin appendages article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Traumatic anserine folliculosis
|
None
| 7,351 |
wikipedia
|
https://en.wikipedia.org/wiki/Traumatic_anserine_folliculosis
| 2021-01-18T18:29:26 |
{"wikidata": ["Q7835821"]}
|
Pregnancy fetishism (also known as maiesiophilia or maieusophoria) is a context where pregnancy is seen by individuals or cultures as an erotic phenomenon.[1] It may involve sexual attraction to women who are pregnant or appear pregnant, attraction to lactation, or attraction to particular stages of pregnancy such as impregnation or childbirth.[2]
## Contents
* 1 Characteristics
* 2 Culture
* 3 See also
* 4 References
* 5 External links
## Characteristics[edit]
There are no particular or preferred elements within maiesiophilia that are common to all maiesiophiliacs. Some may pursue fantasies that are concerned with the circumstances in which a subject may give birth, or to the conditions to which the pregnant subject may find themselves acting upon, such as approaches to mobility, sleeping, and dressing. Particular areas and processes of the body that change during pregnancy may also become the focus of psychological investment, but nudity or sexual activity is not always essential, and in some cases actual pregnancy is not necessary to invoke arousal. In these cases, the appearance of an enlarged abdomen caused by obesity or overeating may be sufficient, or simply the suggestion of a protruding navel.
## Culture[edit]
Pregnancy as represented in 1991 on the More Demi Moore cover of Vanity Fair.
The naked appearance of actress Demi Moore in the advanced stage of pregnancy on the cover of Vanity Fair magazine in 1991 marked the beginning of a period which has since seen pregnancy presented by celebrities as a glamorous state of living, while also creating a market for photographers to produce images of pregnant mothers, and for fashion stylists to introduce "pregnancy styling" to their business.[3]
Pregnancy has proven to be a very popular topic in the world of internet pornography, where searches for 'pregnancy porn' spiked on Pornhub in 2017, with searches increasing 20% since 2014.[4]
Impregnation fantasies are characterized by the arousal or gratification from the possibility, consequences, or risk of impregnation through unprotected vaginal sex. Impregnation fantasies are often indulged by reading erotic literature and role playing with a partner.
## See also[edit]
* Alvinolagnia
* Erotic lactation
* Fat fetishism
* Male pregnancy
## References[edit]
1. ^ Inge Hegeler, Sten Hegeler (1963). An ABZ of Love. University of California. p 94.
2. ^ Longhurst, Robyn (2006). "A Pornography of Birth: Crossing Moral Boundaries" (PDF). ACME: An International E-Journal for Critical Geographies. 5 (2): 221. Archived from the original (PDF) on 2 July 2007. Retrieved 6 December 2007.
3. ^ Associated Press (26 April 2006). "Celebrities make pregnancy seem glamorous". MSNBC.com. Retrieved 18 April 2008.
4. ^ Whitaker, Lenyon. "Pornhub data reveals 'pregnancy porn' searches are on the rise". Metro (May 15, 2017). Retrieved 2018-12-23.
* Katharine Gates (1999). Deviant Desires: Incredibly Strange Sex. Juno Books. ISBN 1-890451-03-7. (p. 96)
## External links[edit]
* Pregnancy Sex Positions: ideas for comfortable sex positions during pregnancy.
* v
* t
* e
Sexual fetishism
Actions, states
* Aquaphilia
* Autassassinophilia
* Coprophilia
* Cuckold / Cuckquean
* Emetophilia
* Erotic hypnosis
* Erotic lactation
* Erotic spanking
* Exhibitionism
* Forced seduction
* Gaining and feeding
* Medical fetishism
* Omorashi
* Paraphilic infantilism (adult baby)
* Pregnancy
* Smoking
* Tickling
* Total enclosure
* Transvestic
* Tightlacing
* Tamakeri
* Urolagnia
* Vorarephilia
* Wet and messy fetishism
Body parts
* Armpit
* Breast
* Belly
* Buttocks
* Eyeball
* Fat
* Feet
* Hands
* Height
* Hair
* Legs
* Navels
* Noses
Clothing
* Boots
* Ballet boots
* Boot worship
* Thigh-high boots
* Clothing
* Corset
* Diapers
* Gloves
* Pantyhose
* Latex
* Rubber and PVC
* Shoes
* Spandex
* Underwear
* Uniforms
Objects
* Balloons
* Dolls
* Latex and PVC
* Robots
* Spandex
Controversial / illegal
* Lust murder
* Necrophilia
* Rape fantasy
* Zoophilia
Culture / media
* Artists
* Fetish art
* Fetish clubs
* Fashion
* Magazines
* Models
Race
* Asian sexual fetishism
* Ethnic pornography
* Sexual racism
Related topics
* BDSM
* FetLife
* International Fetish Day
* Kink
* Leather subculture
* Leather Pride flag
* Sexual roleplay
* Book
* Category
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Pregnancy fetishism
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None
| 7,352 |
wikipedia
|
https://en.wikipedia.org/wiki/Pregnancy_fetishism
| 2021-01-18T18:40:01 |
{"wikidata": ["Q796218"]}
|
## Summary
### Clinical characteristics.
Peutz-Jeghers syndrome (PJS) is an autosomal dominant condition characterized by the association of gastrointestinal polyposis, mucocutaneous pigmentation, and cancer predisposition. Peutz-Jeghers-type hamartomatous polyps are most common in the small intestine (in order of prevalence: in the jejunum, ileum, and duodenum) but can also occur in the stomach, large bowel, and extraintestinal sites including the renal pelvis, bronchus, gall bladder, nasal passages, urinary bladder, and ureters. Gastrointestinal polyps can result in chronic bleeding and anemia and also cause recurrent obstruction and intussusception requiring repeated laparotomy and bowel resection. Mucocutaneous hyperpigmentation presents in childhood as dark blue to dark brown macules around the mouth, eyes, and nostrils, in the perianal area, and on the buccal mucosa. Hyperpigmented macules on the fingers are common. The macules may fade in puberty and adulthood. Individuals with Peutz-Jeghers syndrome are at increased risk for a wide variety of epithelial malignancies (colorectal, gastric, pancreatic, breast, and ovarian cancers). Females are at risk for sex cord tumors with annular tubules (SCTAT), a benign neoplasm of the ovaries, and adenoma malignum of the cervix, a rare aggressive cancer. Males occasionally develop large calcifying Sertoli cell tumors (LCST) of the testes, which secrete estrogen and can lead to gynecomastia, advanced skeletal age, and ultimately short stature, if untreated.
### Diagnosis/testing.
The diagnosis of Peutz-Jeghers syndrome is based on clinical findings. Identification of a heterozygous pathogenic variant in STK11 by molecular genetic testing confirms the diagnosis and allows for family studies.
### Management.
Treatment of manifestations: Routine endoscopic surveillance with polypectomy decreases the frequency of emergency laparotomy and bowel loss resulting from intussusception. Diagnosis and management of small-bowel polyps is challenging. New advances in small-bowel imaging include video capsule endoscopy, CT enterography, and MR enterography. Balloon-assisted enteroscopy allows for removal of deep small-bowel polyps. Occasionally intraoperative enteroscopy and enterotomy is needed for removal of large distal small-bowel polyps. Intussusception and malignancies should be treated in the standard manner.
Prevention of primary manifestations: Although not specifically studied in individuals with PJS, the following could be considered based on family history or other clinical factors: prophylactic mastectomy to manage high risk for breast cancer and prophylactic hysterectomy and bilateral salpingo-oophorectomy after age 35 years or after child bearing has been completed to prevent gynecologic malignancy.
Surveillance: Protocols have been suggested for monitoring stomach, small and large bowel, breasts, testicles, ovaries, uterus, and pancreas by various procedures as early as birth and as frequently as once a year.
Evaluation of relatives at risk: If the pathogenic variant in the family is known, offer molecular genetic testing to at-risk relatives so that morbidity and mortality can be reduced by early diagnosis and prevention of disease through appropriate surveillance and consideration of prophylactic measures in affected family members. If the family variant is not known, offer clinical diagnostic evaluations to all at-risk family members, who will benefit from early treatment and appropriate surveillance.
### Genetic counseling.
Peutz-Jeghers syndrome is inherited in an autosomal dominant manner. However, approximately 45% of affected individuals have no family history of PJS; the exact proportion of cases caused by a de novo pathogenic variant is unknown as the frequency of subtle signs of the disorder in parents has not been thoroughly evaluated and molecular genetic data are insufficient. The risk to the offspring of an individual with a pathogenic STK11 variant is 50%. Once the STK11 pathogenic variant has been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis are possible.
## Diagnosis
### Suggestive Findings
Peutz-Jeghers syndrome (PJS) should be suspected in individuals with the following:
* Two or more PJS-type intestinal polyps
* Mucocutaneous macules
* Gynecomastia in males as a result of estrogen-producing Sertoli cell testicular tumors
* History of intussusception, especially in a child or young adult
PJS-type intestinal polyps. The sine qua non of PJS diagnosis is the hamartomatous gastrointestinal polyp, which is histopathologically characterized by distinctive interdigitating smooth muscle bundles in a characteristic arborizing (branching tree) appearance throughout the lamina propria, particularly of small bowel polyps, and lobular organization, particularly of colonic crypts. Pseudo invasion of misplaced crypts is an innate property of the PJS hamartoma, which may reflect the role of STK11 in cell polarity [Tse et al 2013].
Note: Individuals with PJS also develop many other polyps; polyps showing adenomatous changes frequently arise in the colon and may cause confusion with familial adenomatous polyposis. The histology of gastric PJS polyps can be similar to gastric hyperplastic polyps, thus highlighting the importance of a gastrointestinal pathologist in reviewing polyp histology.
### Establishing the Diagnosis
The diagnosis of PJS is established in a proband with one of the following, based on a European consensus statement [Beggs et al 2010]:
* Two or more histologically confirmed PJS-type hamartomatous polyps
* Any number of PJS-type polyps detected in one individual who has a family history of PJS in at least one close relative
* Characteristic mucocutaneous pigmentation in an individual who has a family history of PJS in at least one close relative
* Any number of PJS-type polyps in an individual who also has characteristic mucocutaneous pigmentation
Identification of a heterozygous pathogenic variant in STK11 by molecular genetic testing (see Table 1) also establishes the diagnosis based on diagnostic criteria from the Mayo Clinic [Riegert-Johnson et al 2008].
Molecular testing approaches can include single-gene testing, use of a multigene panel, and more comprehensive genomic testing:
* Single-gene testing. Sequence analysis of STK11 is performed first and followed by gene-targeted deletion/duplication analysis. Sequence analysis and gene-targeted deletion/duplication analysis of STK11 may also be performed concurrently to reduce turnaround time.
* A multigene panel that includes STK11 and other genes of interest (see Differential Diagnosis) may also be considered. Note: (1) The genes included and the sensitivity of multigene panels vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
* More comprehensive genomic testing (when available) including exome sequencing and genome sequencing may be considered if serial single-gene testing (and/or use of a multigene panel that includes STK11) fails to confirm a diagnosis in an individual with features of PJS. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene or genes that results in a similar clinical presentation).
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
### Table 1.
Molecular Genetic Testing Used in Peutz-Jeghers Syndrome
View in own window
Gene 1Proportion of Peutz-Jeghers Syndrome Attributed to Pathogenic Variants in GeneProportion of Probands with a Pathogenic Variant 2 Detectable by Method
Sequence analysis 3Gene-targeted deletion/duplication analysis 4
STK1194%-96% 5~81% 6~15% 7
Unknown 8NA
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants detected in this gene.
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
4\.
Gene-targeted deletion/duplication analysis detects intragenic deletions or duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
5\.
In a large Dutch study, 73 (96%) of 76 individuals with PJS had an STK11 pathogenic variant [van Lier et al 2010]. In another study 65 (94%) of 69 individuals with PJS had an STK11 pathogenic variant, including 20 (87%) of 23 familial cases and 45 (97.8%) of 46 sporadic cases [Resta et al 2013].
6\.
van Lier et al [2010], Resta et al [2013]
7\.
Includes larger deletions, such as whole-gene deletions of STK11 and smaller intragenic deletions [Le Meur et al 2004, De Rosa et al 2010, Borun et al 2015].
8\.
Of 25 individuals who had PJS but did not have a detectable STK11 pathogenic variant, one had a heterozygous pathogenic variant of the DNA repair enzyme MUTYH that was not observed in 1015 controls [Alhopuro et al 2008]. Of note, pathogenic variants in MUTYH ordinarily cause an autosomal recessive form of adenomatous polyposis coli.
## Clinical Characteristics
### Clinical Description
Peutz-Jeghers syndrome (PJS) is characterized by the association of gastrointestinal polyposis and mucocutaneous pigmentation. The risk for gastrointestinal and extraintestinal malignancies is significantly increased. Distinct benign and malignant gonadal and gynecologic tumors can also be seen. Variable expressivity is common; for example, some affected individuals in families with PJS may have only polyps or perioral pigmentation.
Gastrointestinal polyposis. Peutz-Jeghers-type hamartomatous polyps can occur anywhere in the GI tract, but occur most commonly in the small intestine. The density of polyps is greatest in the jejunum, followed by the ileum, then the duodenum. Polyps can occur elsewhere in the GI tract, including the stomach and large bowel. Polyps have also been reported in the renal pelvis, urinary bladder, ureters, lungs, nares, and gallbladder.
Adenomas also appear with increased prevalence throughout the gastrointestinal tract.
The malignant potential of Peutz-Jeghers-type hamartomatous polyps is unknown; however, the polyps can cause significant complications including bowel obstruction, rectal prolapse, and/or severe gastrointestinal bleeding with secondary anemia requiring multiple emergency laparotomies and bowel resections. The age of onset of symptoms from polyps is variable, with some children developing symptoms within the first few years of life. In one series, 68% of affected individuals had undergone emergency laparotomy by age 18 years. By age ten years, 30% of individuals with PJS had undergone a laparotomy [Hinds et al 2004]. One small single-center retrospective study of 15 individuals concluded that endoscopic management of small-bowel polyps in PJS using double-balloon endoscopy decreased the occurrence of urgent laparotomy by decreasing the mean number of resected polyps larger than 20 mm with each procedure [Sakamoto et al 2011].
Significant interfamilial variability in the age at which polyps first appear is observed, suggesting that the natural history of polyps in a family may be a predictor of severity for offspring. In studies from MD Anderson Cancer Center, the median age at which GI symptoms first appeared was ten years, while the median age at first polypectomy was 13 years [Amos et al 2004]. These data have prompted an earlier start date for surveillance procedures to detect and remove gastrointestinal polyps to decrease malignancy and complications of bowel obstruction [van Lier et al 2010, Latchford et al 2011].
Mucocutaneous pigmentation. Melanocytic macules (MM) are rarely present at birth; they become pronounced in most children before the fifth year, but then may fade in puberty and adulthood. Children often present with dark blue to dark brown mucocutaneous macules around the mouth, eyes, and nostrils, in the perianal area, and on the buccal mucosa. Hyperpigmented macules on the fingers are also common. In one series, 94% of individuals with PJS had perianal MM, 73% had MM that affected the digits, 65% had MM on the buccal mucosa, and 21% had MM at other sites [Utsunomiya et al 1975].
Histologically, increased melanocytes are observed at the epidermal-dermal junction, with increased melanin in the basal cells. No malignancy risk is associated with MM.
Gonadal tumors. Females with PJS are at risk for ovarian sex cord tumors with annular tubules (SCTATs) and mucinous tumors of the ovaries and fallopian tubes. Symptoms include irregular or heavy menstrual periods and, occasionally, precocious puberty due to hyperestrogenism. SCTATs in PJS are bilateral multifocal small tumors with focal calcification and a typically benign course [Young 2005]. In contrast, sporadic SCTATs are large, unilateral, and associated with a 20% risk of malignancy.
In an Italian series of 61 females with PJS, three had ovarian cancer, one was a malignant SCTAT [Resta et al 2013]. In a Dutch series of 69 females with PJS, 2 females had malignant Sertoli cell ovarian tumors and one had ovarian small cell cancer [van Lier et al 2010].
Males occasionally develop large cell calcifying Sertoli cell tumors (LCST) of the testes derived from sperm cord cells. These tumors may secrete estrogen and can lead to gynecomastia, advanced skeletal age, and ultimately short stature, if untreated. Multifocal calcifications are typically seen on testicular ultrasound. Malignant transformation is unusual. Aromatase inhibitors help reverse the hormonal effects of Sertoli cell tumors including reduction of gynecomastia and slowing of linear bone growth and bone age [Crocker et al 2014]. In a series including 64 males with PJS, one testicular seminoma was reported [van Lier et al 2010].
Malignancy. Individuals with PJS are at increased risk for intestinal and extraintestinal malignancies.
### Table 2.
Cumulative Risk of Cancers in Peutz-Jeghers Syndrome
View in own window
Cancer SiteGeneral Population RiskPeutz-Jeghers Syndrome
RiskMean Age at Diagnosis
Colorectal5%39%42-46 years
Stomach<1%29%30-40 years
Small Bowel<1%13%37-42 years
Breast12.4%32%-54%37-59 years
Ovarian (mostly SCTAT)1.6%21%28 years
Cervix (adenoma malignum)<1%10%34-40 years
Uterus2.7%9%43 years
Pancreas1.5%11%-36%41-52 years
Testicular (Sertoli cell tumor)<1%9%6-9 years
Lung6.9%7%-17%47 years
Adapted from Syngal et al [2015]
SCTAT = sex-cord tumor with annular tubules
Colorectal and gastric cancers can arise from adenomas that are commonly found in individuals with PJS. A marked increase in cancer incidence after age 50 years is notable.
Breast cancer and ovarian cancers can occur at early ages in Peutz-Jeghers syndrome. The breast cancer risk in women with PJS may approach that of women who have a pathogenic variant in BRCA1 or BRCA2. Some families with PJS report relatives with early-onset breast cancer, suggesting that some family members with a pathogenic variant may on occasion develop breast or other cancers without having symptoms from the hamartomatous polyps.
Cervical cancer. Adenoma malignum is a rare well-differentiated adenocarcinoma of the uterine cervix. Presenting symptoms include bleeding or a mucoid, watery vaginal discharge. Histologic diagnosis can be difficult on small pathologic samples. The five-year survival after surgery is 60% [Tsuda et al 2005].
### Genotype-Phenotype Correlations
Data on genotype-phenotype correlation related to STK11 pathogenic variants are conflicting. Further analysis of pooled registry data is needed to better characterize genotype-phenotype correlations and confirm malignancy risks.
In a study of 297 individuals with PJS, the type or site of the STK11 pathogenic variant did not influence cancer risk [Lim et al 2004]. Initial reports that pathogenic variants in exon 3 [Lim et al 2004] or exon 6 [Mehenni et al 2007] were associated with an increased cancer risk have not been replicated by subsequent studies. A review of 419 affected individuals found that the variant type and site within the functional domains of the expressed protein did not affect cancer risk [Hearle et al 2006a].
In contrast, Amos et al [2004] found that individuals who had pathogenic STK11 variants that predicted premature truncation and those who tested negative for pathogenic variants had similar ages of onset for first-reported polyps or polypectomy, and those with missense variants had later onset for these symptoms. Salloch et al [2010] similarly found that persons with pathogenic STK11 variants that predicted premature truncation had more gastrointestinal surgeries, a higher polyp count, an earlier age of first polypectomy, and a greater risk of melanoma than persons with other pathogenic variants.
The risk for small-bowel intussusception was not influenced by STK11 variant status [Hearle et al 2006b].
Pathogenic variants affecting protein kinase domain XI correlated with a 90% (9/10) incidence of GI polyp dysplasia compared to an 11.8% (2/17) incidence of polyp dysplasia in individuals with pathogenic variants affecting other regions of the protein [Wang et al 2014].
### Penetrance
To date all reported individuals with pathogenic variants in STK11 have shown clinical manifestations.
### Nomenclature
The following terms have also been used for PJS:
* Polyp and spots syndrome
* Inherited hamartomatous polyps in association with mucocutaneous melanocyte macules
* Hutchinson Weber-Peutz syndrome
* Perioral lentiginosis (sometimes used inappropriately as a synonym for PJS)
### Prevalence
Birth prevalence has not been reliably established; estimates range widely from 1:25,000 to 1:280,000 [Tchekmedyian et al 2013].
PJS can occur in any racial or ethnic group.
## Differential Diagnosis
Table 3 summarizes the differential diagnosis of Peutz-Jeghers syndrome (PJS).
Juvenile polyposis syndrome (JPS) is characterized by a predisposition to multiple hamartomatous polyps in the gastrointestinal (GI) tract, specifically in the stomach, small intestine, colon, and rectum. The term "juvenile" refers to the type of polyp, not the age of onset of polyps. Juvenile polyps are hamartomas that show a normal epithelium with a dense stroma, an inflammatory infiltrate, and a smooth surface with dilated, mucus-filled cystic glands in the lamina propria. Most individuals with JPS have some polyps by age 20 years. The number of polyps is highly variable. Most are benign. The risk of developing GI cancers in families with JPS ranges from 9% to 50%. Although most of this increased risk is attributed to colon cancer, cancers of the stomach, upper GI tract, and pancreas have been reported. JPS is distinguished from PJS by the lack of melanotic macules and the histology of polyps. Approximately 20% of individuals with JPS have pathogenic variants in SMAD4; about 20% have pathogenic variants in BMPR1A. JPS is inherited in an autosomal dominant manner.
Hereditary mixed polyposis syndrome (HMPS) (OMIM 601228). A family history of JPS is found in 20%-50% of individuals with hereditary mixed polyposis syndrome. HMPS is an autosomal dominant condition with variable penetrance consisting of multiple types of colorectal polyps including juvenile and adenomatous polyps. Affected individuals are at increased risk for colorectal cancer. HMPS can be caused either by mutation of BMPR1A or by a duplication of 15q15.3q22.1 that leads to increased expression of GREM1 [Jaeger et al 2012]. Some families with mixed hereditary polyposis syndrome have SMAD4 pathogenic variants.
PTEN hamartoma tumor syndrome (PHTS), an autosomal dominant cancer syndrome caused by mutation of PTEN, includes Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, PTEN-related Proteus syndrome, and a Proteus-like syndrome. The extraintestinal manifestations are more pronounced than intestinal polyposis. The features of Cowden syndrome that distinguish it from PJS include facial trichilemmomas, mucosal papillomas, acral keratoses, macrocephaly, and tumors of the thyroid, breast, and endometrium. The distinguishing features of Bannayan-Riley-Ruvalcaba syndrome include macrocephaly, intestinal polyposis, and lipomas. Proteus-like syndrome is undefined but refers to individuals with significant clinical features of Proteus syndrome who do not meet the diagnostic criteria for Proteus syndrome.
Unexplained hamartomatous mixed polyposis. In a study of 49 unrelated persons with unexplained hamartomatous mixed polyposis, Sweet et al [2005] determined that 22% had various germline pathogenic variants.
* Of 14 individuals with juvenile-type polyposis: two had pathogenic variants in ENG (encoding endoglin), a gene associated with hereditary hemorrhagic telangiectasia; one had a hemizygous deletion encompassing PTEN and BMPR1A; and one had a SMAD4 pathogenic variant.
* Of 23 individuals with hyperplastic/mixed polyposis, two had PTEN pathogenic variants.
* Of nine individuals with an unknown hamartomatous polyposis, pathogenic variants were seen in STK11 (4), BMPR1A (2), and SMAD4 (1).
Carney complex is an autosomal dominant disorder characterized by skin pigmentary abnormalities; myxomas, endocrine tumors or overactivity, and schwannomas. Pale brown to black lentigines are the most common presenting feature of Carney complex and typically increase in number at puberty. Cardiac myxomas occur at a young age, may occur in any or all cardiac chambers, and manifest as intracardiac obstruction of blood flow, embolic phenomena, and/or heart failure. Other sites for myxomas include the skin, breast, oropharynx, and female genital tract. Primary pigmented nodular adrenocortical disease, which causes Cushing syndrome, is the most frequently observed endocrine tumor, occurring in approximately 25% of affected individuals. Large-cell calcifying Sertoli cell tumors are observed in one third of affected males within the first decade and in almost all adult males. Up to 75% of individuals have multiple thyroid nodules, most of which are thyroid follicular adenomas. Clinically evident acromegaly from a growth hormone (GH)-producing adenoma is evident in approximately 10% of adults. Psammomatous melanotic schwannoma, a rare tumor of the nerve sheath, occurs in an estimated 10% of affected individuals. Despite some clinical overlap between Carney complex and Peutz-Jeghers syndrome, no individuals with Carney complex have been found to have pathogenic variants in STK11. About 60% of individuals have pathogenic variants in PRKAR1A.
### Table 3.
Hereditary Cancer Syndromes Showing Signs and Symptoms that Overlap with PJS
View in own window
SyndromeGene(s)PigmentationGI TumorsSertoli Cell TumorsCancersOther
PJSSTK11Facial++ Mucosal+++Adenoma+
Hamartoma++++/–Colon, gastric, cervical, ovarian, breast, pancreatic, lungHyper-estrogenism
JPSSMAD4
BMPR1A–Adenoma+
Hamartoma+++–ColonHeart defects?
CSPTENAxillary+ Inguinal+ Facial+Adenoma+
Hamartoma+++–Breast, thyroid, endometriumTrichilemmoma, skin hamartoma, hyperplastic polyps, macrocephaly, breast fibrosis
CCPRKAR1AFacial+ Mucosal+–++ThyroidMyxomas of skin & heart
FAPAPC–Adenoma+++–Colon, brainDesmoid tumors, osteomas, CHRPE
HNPCCMLH1
MSH2
MSH3
MSH6
PMS1
PMS2Adenoma+–Endometrial, gastric, renal pelvis & ureter, ovarianSebaceous adenoma
\+
= presence of sign/symptom (# of +s indicates relative frequency of sign/symptom for the condition); ± = an occasional or rare sign/symptom; ? = anecdotal association; CC = Carney complex; CHRPE = congenital hypertrophy of the retinal pigment epithelium; CS = Cowden syndrome; FAP = familial adenomatous polyposis; HNPCC = hereditary non-polyposis colorectal cancer; JPS = juvenile polyposis syndrome
The differential diagnosis of oral pigmented lesions includes the following:
* The Laugier-Hunziker syndrome is characterized by the presence of perioral, digit and nailbed lentiginosis (small, well-demarcated; dark-brown to blue-black in color). It occurs in 1:8,300 to 1:29,000 births. This condition usually develops in adults and the hyperpigmentation is progressive. Laugier-Hunziker syndrome has not been associated with any known exposure and has not been reported to occur in families [Wang et al 2012].
* A fixed drug reaction
* A normal variant, especially in African Americans [Bishop et al 2004]
The differential diagnosis of some of the rare tumors observed in PJS includes:
* Sex cord tumors with annular tubules (SCTAT); 50% are associated with Peutz-Jeghers syndrome; the remainder may occur as an isolated finding.
* Calcifying Sertoli tumors of the testes and adenoma malignum of the cervix in women; these may also occur as an isolated finding or in other disorders.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and need for clinical follow up in an individual diagnosed with Peutz-Jeghers syndrome (PJS), the following initial evaluations are recommended:
* Upper endoscopy plus small bowel examination (MR enterography or wireless capsule endoscopy) beginning at age eight years or when symptoms occur
* Colonoscopy beginning at age eight years
* In women, gynecologic and breast examinations and (after age 18 years) MRI
* In men, testicular examination and testicular ultrasound examination, if clinically indicated
* Consultation with a clinical geneticist and/or genetic counselor
### Treatment of Manifestations
Polyps. Once the burden of gastrointestinal polyps has been established by endoscopy and imaging studies, prophylactic polypectomy of polyps >1cm is performed. This strategy has two goals:
* To decrease the sequelae of large polyps including bleeding, anemia, obstruction, and intussusception
* To reduce the risk for cancer by the malignant transformation of PJS-type polyps
The luminal polyp-related complications arise in childhood whereas cancer in PJS is typically seen in adulthood. Some evidence indicates that routine endoscopy and intraoperative enteroscopy with polypectomy decreases the frequency of emerging laparotomy and bowel loss [Pennazio & Rossini 2000, Edwards et al 2003, Oncel et al 2004]. From St. Mark’s PJS registry of 51 affected individuals who underwent surveillance endoscopies, none had emergency surgical interventions and no GI luminal cancers were diagnosed [Latchford et al 2011]. In surveillance endoscopies in affected individuals by age 18 years, 17/28 had large gastroduodenal or colonic polyps (>1 cm). These studies demonstrate that endoscopic surveillance and polypectomy in PJS is safe.
Distal small-bowel polyps that are beyond the reach of conventional endoscopy have been difficult to manage. Until recently, barium contrast upper-gastrointestinal series with a small-bowel follow through has been recommended. However, recent advances allow better diagnosis and eradication of small-bowel polyps, oftentimes without laparotomy and with a decrease in the radiation burden related to frequent surveillance:
* Video capsule endoscopy (VCE) allows for better visualization of the small-bowel polyps than barium x-rays and is recommended as a first-line surveillance procedure. In children, the capsule can be deployed in the duodenum after upper endoscopy [Parsi & Burke 2004, Burke et al 2005, Mata et al 2005, Schulmann et al 2005]. See Note.
* Magnetic resonance enterography (MRE) is a reliable procedure for the detection of larger small-bowel polyps with similar sensitivity to VCE and avoids the radiation exposure of CT enterography [Caspari et al 2004, Gupta et al 2010]. CT and MR enteroclysis are alternative procedures but are less well tolerated. See Note.
* Balloon-assisted enteroscopy can remove distal small-bowel polyps with or without laparotomy [Ohmiya et al 2005, Ross et al 2006, Gao et al 2010]. Safety in those with PJS has been demonstrated in a few studies. Balloon-assisted enteroscopy and polypectomy should decrease the need for intraoperative enteroscopy or enterotomy, and should be reserved for affected individuals with many large and distal small-bowel polyps.
Note: (1) VCE was preferred by individuals and detected more large polyps than MRE [Urquhart et al 2014]. (2) In three individuals in a study by Gupta et al [2010], MRE detected polyps >15 mm that were not detected by VCE.
Intussusception should be treated in a standard manner.
Malignancies should be treated in a standard manner. Conservative management of gonadal tumors in males and females is appropriate.
### Prevention of Primary Manifestations
Although not specifically studied in PJS, prophylactic mastectomy may be considered to manage the increased risk for breast cancer based on the family history or other clinical factors. Prophylactic hysterectomy and bilateral salpingo-oophorectomy to prevent gynecologic malignancy in women may be considered. In some disorders with a high risk for malignancy (e.g., HNPCC), evidence supports this strategy [Schmeler et al 2006].
### Surveillance
The surveillance program for the multiple organs at risk for cancer is outlined in Table 4. Note: The effect of such surveillance on morbidity and mortality has not been evaluated in controlled trials.
From birth, an annual history and physical examination with attention to testicular examination and routine blood work is recommended. A boy age 13 years with PJS was recently described as developing an unusually early presentation of small-bowel adenocarcinoma, thus supporting screening in childhood as illustrated in Table 4 [Wangler et al 2013].
### Table 4.
Screening and Surveillance Guidelines for Peutz-Jeghers Syndrome
View in own window
SiteProcedureAge at Initial Screening (yrs)Interval
StomachUpper endoscopy8, 18 13 yrs 1
Small intestineCapsule endoscopy or MRE 28, 18 33 yrs
Large intestineColonoscopy8, 18 13 yrs 1
BreastBreast self-examination181x/mo
Clinical breast exam6 mos
Breast MRI or digital mammography 4, 5, 6251 yr
Ovary, cervix, uterusTransvaginal ultrasound & serum CA 125;
pelvic exam w/pap smear 618-201 yr
PancreasMRI-MRCP or endoscopic ultrasound301-2 yrs
TestesTesticular exam; ultrasound if symptomatic or abnormality on examBirth to teen yrs1 yr
Adapted from Syngal et al [2015]
MRCP = magnetic resonance cholangiopancreatography; MRE = magnetic resonance enterography
1\.
If significant polyps are present at baseline, repeat upper endoscopy/colonoscopy every three years. If no significant polyps are present at baseline, repeat at age 18 years and then every three years.
2\.
CT enterography may be used as an alternative. The use of MR enterography allows for simultaneous surveillance for pancreatic cancer.
3\.
If few or no polyps at baseline, repeat at age 18 years.
4\.
Digital mammography if MRI not available
5\.
Discuss prophylactic mastectomy.
6\.
Discuss prophylactic hysterectomy and oophorectomy.
### Agents/Circumstances to Avoid
No agents that increase the risk for polyp development or for cancers have been described.
### Evaluation of Relatives at Risk
It is appropriate to evaluate apparently asymptomatic older and younger at-risk relatives of an affected individual in order to identify as early as possible those who would benefit from initiation of treatment and preventive measures.
If the pathogenic variant in the family is known, it is appropriate to offer molecular genetic testing for the known pathogenic or likely pathogenic variant to at-risk relatives. Morbidity and mortality can be reduced in those individuals identified to have the family-specific variant by means of:
* Early diagnosis and treatment;
* Surveillance as outlined in Surveillance.
If the pathogenic variant in the family is not known, it is appropriate to offer:
* Clinical diagnostic evaluations to identify those family members who will benefit from early treatment;
* Surveillance as outlined in Surveillance to all first-degree relatives whether or not they meet diagnostic criteria.
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Therapies Under Investigation
Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.
### Other
Several animal models of PJS have been generated using STK11 knockout mice [Karuman et al 2001, Bardeesy et al 2002, Miyoshi et al 2002, Nakau et al 2002, Wei et al 2005]. Gastrointestinal hamartomatous polyposis in STK11+/– mice mimics human PJS polyps with the unique smooth muscle arborization. In these animal models, upregulation of cyclooxygenase-2 (COX-2) in polyp tissue was noted [Rossi et al 2002]. Overexpression of COX-2 in human PJS hamartomas and PJS-associated cancers has also been detected [McGarrity et al 2003, Wei et al 2003]. COX-2 inhibition in mice using celecoxib suppresses polyp growth [Udd et al 2004]. Polyp burden in STK11 (Lkb1) heterozygous (+/–) knockout mice was reduced by 86% among mice who had developed polyps and were then treated with 1500-ppm celecoxib.
Selective COX-2 inhibitors have been approved for the prevention of colorectal polyps in familial adenomatous polyposis [Lynch 2010]; to date, however, no clinical trials in the US are studying efficacy of COX-2 inhibitors in reducing polyp formation in individuals with PJS. Increased cardiovascular and cerebrovascular adverse events with selective COX-2 inhibitors limit their use.
Observation of hyperactivation of mTOR in hereditary harmartoma syndrome and a variety of cancers suggests that mTOR inhibitors may be useful in the management of PJS [van Veelen et al 2011]. Wei et al [2008] and Wei et al [2009] reported significant reduction in tumor burden in STK11+/– mice treated with rapamycin compared with that in mice without rapamycin treatment. Treatment begun before the onset of polyposis resulted in more dramatic reduction than treatment begun after onset. In another study in STK11+/– mice oral rapamycin intake was associated with a significant reduction in microvessel growth in polyps as well as in tumor burden [Robinson et al 2009].
In addition, in two small trials in persons with tuberous sclerosis complex, treatment with rapamycin induced regression of the astrocytomas [Franz et al 2006] and reduced facial angiofibroma [Hofbauer et al 2008]. Whether rapamycin would decrease polyp growth in PJS has not been documented in human studies. The mTOR inhibitor, everolimus, caused partial regression of a pancreatic cancer in an individual with PJS. Induction of apoptosis in colon polyps was also noted [Klümpen et al 2011].
These findings suggest that mTOR inhibitors are an option to investigate for management of polyposis in PJS.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Peutz-Jeghers Syndrome
|
c0031269
| 7,353 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK1266/
| 2021-01-18T21:03:52 |
{"mesh": ["D010580"], "synonyms": ["PJS"]}
|
For a general phenotypic description and a discussion of genetic heterogeneity of Miyoshi muscular dystrophy, see MMD1 (254130).
Clinical Features
Linssen et al. (1998) reported 2 unrelated Dutch families with Miyoshi muscular dystrophy. The phenotype was similar to that described in MMD1, except that the muscle weakness and atrophy were asymmetric from the onset and remained so in 2 affected individuals.
Mapping
In 3 unrelated Dutch families with Miyoshi myopathy, Linssen et al. (1998) excluded linkage to the MMD1 locus on chromosome 2p. Genomewide linkage analysis showed putative linkage to a 23-cM region on chromosome 10p in 2 families. The families were small, and the maximum lod score was 2.578 with 9 markers in this region, including D10S2325. Linssen et al. (1998) noted that this was the maximum lod score that could be obtained in these 2 families. A fourth family was not linked to either 2p or 10p, indicating further genetic heterogeneity.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
MIYOSHI MUSCULAR DYSTROPHY 2
|
c1850808
| 7,354 |
omim
|
https://www.omim.org/entry/613318
| 2019-09-22T15:59:01 |
{"doid": ["0070200"], "omim": ["613318"], "orphanet": ["45448"], "synonyms": ["Alternative titles", "MIYOSHI MYOPATHY 2"]}
|
High anorectal malformation is a rare, genetic, non-syndromic subtype of anorectal malformation, resulting from a developmental defect during embryogenesis, characterized by a wide spectrum of anorectal anomalies, with or without a rectourogenital fistula, located above the pubococcygeal line (i.e. anorectal agenesis, rectal agenesis, atresia, or stenosis). Patients may present with meconuria, pyuria, strangury, and fecal and urinary incontinence.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
High isolated anorectal malformation
|
c0345210
| 7,355 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=171201
| 2021-01-23T17:40:36 |
{"umls": ["C0345210"], "icd-10": ["Q42.0", "Q42.1"]}
|
A number sign (#) is used with this entry because the Potocki-Lupski syndrome (PTLS) is a contiguous gene syndrome caused by duplication of chromosome 17p11.2.
See also Smith-Magenis syndrome (SMS; 182290), which is associated with the reciprocal deletion of chromosome 17p11.2 and shows overlapping clinical features.
Description
Potocki-Lupski syndrome is a developmental disorder characterized by hypotonia, failure to thrive, mental retardation, pervasive developmental disorders, and congenital anomalies. All reported cases have occurred sporadically without bias in the parental origin of rearrangements. Most duplications are 3.7 Mb in size and only identifiable by array comparative genomic hybridization (CGH) analysis. Approximately 60% of PTLS patients harbor a microduplication of chromosome 17p11.2 reciprocal to the common recurrent 3.7-Mb microdeletion in SMS (summary by Shchelochkov et al., 2010).
Clinical Features
Brown et al. (1996) described 2 unrelated males with developmental delay and mild dysmorphic facial features associated with duplication of 17p11.2. The extent of the duplicated region was determined using single-copy DNA probes and was confirmed by fluorescence in situ hybridization. Brown et al. (1996) raised the question of whether this was a reciprocal of the Smith-Magenis syndrome deletion.
Potocki et al. (2000) reported 7 unrelated patients evaluated for developmental delay who had de novo duplications of the same region deleted in SMS. Clinical features included mild mental retardation, behavioral abnormalities such as attention-deficit, hyperactivity, and autism, short stature, and dental abnormalities such as malocclusion and crowded teeth. Two patients had dysmorphic facies with triangular facies, smooth philtrum, high-arched palate, frontal bossing, and mandibular and maxillary hypoplasia. A third patient had a submucous cleft palate and bifid uvula. In general, however, the phenotype was less severe than that seen in SMS deletion syndrome.
Potocki et al. (2007) performed systematic multidisciplinary clinical evaluations in a subset of 10 subjects, including 1 subject who harbored the smallest duplication identified to that time. Apart from developmental delay, language impairment, and cognitive impairment, the most frequent clinical features of PTLS were hypotonia, poor feeding and failure to thrive in infancy, oral-pharyngeal dysphagia, autistic features, obstructive and central sleep apnea, structural cardiovascular abnormalities, electroencephalogram (EEG) abnormalities, and hypermetropia. Features reported in more than 50% of patients with the reciprocal SMS deletion were not observed or were seen only infrequently in the duplication 17p11.2 syndrome, including short stature, hearing impairment, otolaryngologic abnormalities, ophthalmic abnormalities such as myopia and iris hamartomata, genitourinary and/or renal anomalies, clinically significant scoliosis, and hypercholesterolemia. Potocki et al. (2007) suggested that the vast majority of PTLS patients showed features of autistic spectrum disorder.
Greco et al. (2008) reported 3 girls with PTLS and de novo duplication of chromosome 17p11.2. Clinical features included neonatal hypotonia, failure to thrive, and severe language delay. There were variable dysmorphic features, including triangular face, microcephaly, trigonocephaly, hypertelorism, and flat philtrum. Common features included wide nasal bridge, epicanthal folds, strabismus, large mouth, wide third phalanges on the hands, and increased gap between the first and second toes. Cognitive testing showed severe, moderate, and mild mental retardation, respectively. In contrast to the findings of Potocki et al. (2007), none of the 3 girls had features of autism by several specific diagnostic scales.
Cytogenetics
Using pulsed field gel electrophoresis (PFGE), Potocki et al. (2000) identified a unique junction fragment, of the same apparent size, in each patient with multiple congenital anomalies and mental retardation examined by them. Further molecular analyses suggested that the de novo 17p11.2 duplication was preferentially paternal in origin, arose from unequal crossing-over due to homologous recombination between flanking repeat gene clusters, and probably represents the reciprocal recombination product of the SMS deletion.
Potocki et al. (2007) reported the molecular assays of 35 subjects with dup(17)(p11.2p11.2). Of these subjects, 22 harbored a 'common' duplication (approximately 3.7 Mb), and 13 harbored nonrecurrent duplications ranging in size from 1.3 to 15.2 Mb, as determined by multiple independent molecular assays.
Zhang et al. (2010) identified an uncommon recurrent 5-Mb duplication at chromosome 17p11.2 in 2 (2.7%) of 74 patients with PTLS, including 35 of whom had not been characterized at the molecular level. This duplication was the reciprocal of an uncommon 5-Mb deletion found in SMS patients (Shaw et al., 2004). The duplicated region encompassed the entire common 3.7-Mb duplication, and the PTLS patients did not show additional clinical features. Further analysis showed that the duplications shared the same recombination hotspot with the reciprocal SMS-associated deletion, and occurred in proximity to a recently delineated allelic homologous recombination (AHR) hotspot-associated sequence motif. Among the remaining uncharacterized PTLS patients studied by Zhang et al. (2010), 25 had the common 3.7-Mb duplication, and 8 had nonrecurrent duplications with continuous copy number gain ranging in size from 0.41 to 13.3 Mb. Four (50%) of the 8 nonrecurrent duplications had complex 17p rearrangements associated with replication-based mechanisms. Together with previously reported PTLS duplications representing a total of 74 cases, Zhang et al. (2010) concluded that 50 (67.6%) have common recurrent duplications, 2 (2.7%) have uncommon recurrent duplications, and 22 (29.7%) have nonrecurrent duplications. Thus, approximately 70% of PTLS duplications are recurrent and occur by the NAHR mechanism. The smallest region of overlap was reduced to 125 kb on chromosome 17p11.2, which included the RAI1 gene (607642), suggesting that this gene is mainly responsible for the phenotype.
Kaminsky et al. (2011) presented the largest copy number variant case-control study to that time, comprising 15,749 International Standards for Cytogenomic Arrays cases and 10,118 published controls, focusing on recurrent deletions and duplications involving 14 copy number variant regions. Compared with controls, 14 deletions and 7 duplications were significantly overrepresented in cases, providing a clinical diagnosis as pathogenic. The 17p11.2 duplication was identified in 15 cases and no controls for a p value of 0.0008 and a frequency of 1 in 1,050 cases.
Diagnosis
Potocki et al. (2000) initially hypothesized that patients with 17p11.2 duplication did not come to medical attention because of their milder phenotype. However, the findings of Potocki et al. (2007) revealed that these patients may have substantial medical illness as well as neurobehavioral abnormalities that, except for the developmental delay, may go unrecognized until later infancy or childhood. Potocki et al. (2007) suggested that most patients likely elude an etiologic diagnosis because of the limitations of conventional cytogenetic analyses.
Pathogenesis
Nonallelic homologous recombination between region-specific low-copy repeats (LCRs) (also known as 'segmental duplications') is a major cause of DNA rearrangements associated with many genomic disorders (Stankiewicz and Lupski, 2002). The proximal short arm of chromosome 17 is particularly rich in LCRs and is a regional locus for 4 genomic disorders: Charcot-Marie-Tooth type 1A (CMT1A; 118220); hereditary neuropathy with liability to pressure palsies (HNPP; 162500); Smith-Magenis syndrome (182290); and the 17p11.2 duplication syndrome (Potocki et al., 2007).
Shaw et al. (2002) analyzed the haplotypes of 14 families of patients with SMS and 6 families of patients with duplication of the same region using microsatellite markers directly flanking the SMS common deletion breakpoints. The data indicated that the deletion and its reciprocal duplication of chromosome 17p11.2 result from unequal meiotic crossovers mediated through nonallelic homologous recombination (NAHR) that occurs via both interchromosomal and intrachromosomal exchange events between the proximal and distal SMS repeats. There appeared to be no parental-origin bias associated with common SMS deletions and the reciprocal duplications.
Bi et al. (2003) reported a recombination hotspot associated with both the common SMS deletion and the reciprocal duplication, dup(17)(p11.2p11.2), demonstrating the reciprocity of the crossover events as had been demonstrated for HNPP and CMT1A.
Liu et al. (2011) assembled 2 patient cohorts with reciprocal genomic disorders, deletion-associated Smith-Magenis syndrome and duplication-associated Potocki-Lupski syndrome. By assessing the full spectrum of rearrangement types from the 2 cohorts, Liu et al. (2011) found that complex rearrangements (those with more than 1 breakpoint) are more prevalent in copy-number gains (17.7%) than in copy-number losses (2.3%), an observation that supports a role for replicative mechanisms in complex rearrangement formation. Interestingly, for nonallelic homologous recombination-mediated recurrent rearrangements, Liu et al. (2011) showed that crossover frequency is positively associated with the flanking low-copy repeat (LCR) length and inversely influenced by the inter-LCR distance. To explain this, they proposed that the probability of ectopic chromosome synapsis increases with increased LCR length, and that ectopic synapsis is a necessary precursor to ectopic crossing-over.
Nomenclature
Potocki-Lupski syndrome was the first predicted reciprocal microduplication syndrome described, being the homologous recombination reciprocal of the Smith-Magenis syndrome microdeletion del(17)(p11.2p11.2). Because the cytogenetic nomenclature can be cumbersome when used to refer to affected individuals, Potocki et al. (2007) proposed that the 17p11.2 microduplication syndrome be referred to by the eponym 'Potocki-Lupski syndrome' (PTLS).
Animal Model
Mice with a heterozygous duplication, Dp(11)17, of the region on mouse chromosome 11 that is syntenic to human chromosome 17 are underweight and show behavioral anomalies such as impaired contextual fear conditioning (Walz et al. (2003, 2004)). Walz et al. (2006) generated compound heterozygous mice with a Dp(11)17 allele and a null Rai1 (607642) allele, thus resulting in normal disomic gene dosage of Rai1. Normal Rai1 dosage rescued many of the phenotypes observed in heterozygous Dp(11)17 mice, including normalization of body weight and partial normalization of behavior. The phenotype was rescued despite altered trisomic copy number of the other 18 or so genes in the region. Walz et al. (2006) concluded that duplication of Rai1 is responsible for decreased body weight in Dp(11)17 mice and that Rai1 is a dosage-sensitive gene involved in body weight control and complex behavioral responses.
Molina et al. (2008) found that the PTLS mouse model, Dp(11)17/+, recapitulated some of the physical and neurobehavioral phenotypes present in patients. Dp(11)17/+ male mice displayed normal home-cage behavior, with the exception of decreased vocalization during handling and decreased nesting behavior compared to wildtype mice. Dp(11)17/+ mice also showed increased anxiety, increased dominant behavior in specific tests, a subtle impairment in the preference for a social target versus an inanimate target, and an impaired response to social novelty. These behaviors were interpreted as representing autistic features in humans. Dp(11)17/+ mice had lower body weight and lower brain weight at 3 months of age compared to wildtype, although the percentage of brain weight to total weight was higher in the transgenic mice. Gene expression array analysis and PCR studies showed overexpression of several genes, including Rai1, in the hippocampus of transgenic mice. The data also showed that candidate genes influencing behavior included not only most of the duplicated genes, but also normal-copy genes that flanked the engineered interval.
INHERITANCE \- Isolated cases GROWTH Height \- Short stature (less common) Other \- Failure to thrive HEAD & NECK Head \- Broad forehead \- Microcephaly (less common) \- Trigonocephaly Face \- Triangular face \- Smooth philtrum \- Micrognathia Eyes \- Downslanting palpebral fissures \- Hypertelorism \- Hypermetropia Nose \- Long nasal tip Mouth \- High-arched palate \- Oral-pharyngeal dysphagia \- Large mouth Teeth \- Malocclusion \- Crowded teeth CARDIOVASCULAR Heart \- Structural cardiovascular abnormalities \- Atrial septal defect \- Patent foramen ovale RESPIRATORY \- Sleep apnea ABDOMEN Gastrointestinal \- Poor feeding \- Gastroesophageal reflux SKELETAL Spine \- Scoliosis (less common) NEUROLOGIC Central Nervous System \- Developmental delay \- Mental retardation, mild \- Hypotonia \- Speech delay \- EEG abnormalities \- No overt seizures \- Delayed myelination \- Hypoplastic corpus callosum Behavioral Psychiatric Manifestations \- Autistic features \- Attention-deficit disorder \- Hyperactivity ENDOCRINE FEATURES \- Hypothyroidism (less common) LABORATORY ABNORMALITIES \- Decreased cholesterol (less common) MISCELLANEOUS \- Variable phenotype \- Contiguous gene duplication syndrome MOLECULAR BASIS \- Caused by interstitial duplication (3.7Mb) of 17p11.2 ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
POTOCKI-LUPSKI SYNDROME
|
c2931246
| 7,356 |
omim
|
https://www.omim.org/entry/610883
| 2019-09-22T16:03:56 |
{"doid": ["0060853"], "mesh": ["C538355"], "omim": ["610883"], "orphanet": ["1713"], "synonyms": ["Alternative titles", "CHROMOSOME 17p11.2 DUPLICATION SYNDROME"], "genereviews": ["NBK447920"]}
|
Joubert syndrome is disorder of brain development that may affect many parts of the body. It is characterized by the absence or underdevelopment of the cerebellar vermis (a part of the brain that controls balance and coordination) and a malformed brain stem (connection between the brain and spinal cord). Together, these cause the characteristic appearance of a molar tooth sign on MRI. Signs and symptoms can vary but commonly include weak muscle tone (hypotonia); abnormal breathing patterns; abnormal eye movements; ataxia; distinctive facial features; and intellectual disability. Various other abnormalities may also be present. Joubert syndrome may be caused by mutations in any of many genes. Inheritance is usually autosomal recessive, but rarely it may be X-linked recessive. Treatment is supportive and depends on the symptoms in each person.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Joubert syndrome
|
c0431399
| 7,357 |
gard
|
https://rarediseases.info.nih.gov/diseases/6802/joubert-syndrome
| 2021-01-18T17:59:41 |
{"mesh": ["C536293"], "omim": ["213300"], "umls": ["C0431399"], "orphanet": ["475"], "synonyms": ["Cerebelloparenchymal disorder 4", "Cerebellar vermis agenesis", "Joubert-Boltshauser syndrome", "JBTS1", "CPD4", "Cerebellooculorenal syndrome 1", "CORS1", "Joubert syndrome 1"]}
|
A number sign (#) is used with this entry because atrial septal defect-2 (ASD2) is caused by heterozygous mutation in the GATA4 gene (600576) on chromosome 8p23.
For discussion of genetic heterogeneity in atrial septal defect, see ASD1 (108800).
Clinical Features
Garg et al. (2003) identified a large kindred spanning 5 generations in which 16 individuals had congenital heart defects. Detailed clinical evaluations reviewed for all available family members demonstrated an autosomal dominant pattern of inheritance. All affected family members had atrial septal defects. Eight individuals had additional congenital heart defects, including ventricular septal defects (VSD), atrioventricular septal defects (AVSD), pulmonary valve thickening, or insufficiency of the cardiac valves. Ten of the 16 affected members required surgical repair of the heart defect. Unlike the familial cases of cardiac septal defects associated with mutations in NKX2.5 (600584) or TBX5 (601620), neither the cardiac conduction system nor other organs were affected in this kindred, suggesting that the congenital heart defects were isolated and not associated with syndromic disease.
Hirayama-Yamada et al. (2005) reported a 4-generation family with ASD in which affected members were found to have the same mutation in the GATA4 gene (600576.0002) as the second family described by Garg et al. (2003). A deceased member of the family in whom the mutation was identified was said to have had dextrocardia rather than ASD.
Mapping
In a large kindred spanning 5 generations in which 16 individuals had congenital heart defects, Garg et al. (2003) excluded mutations in the NKX2.5 and TBX5 genes. Linkage analysis identified an area in chromosome 8p23-p22 that showed a lod score of 5.7 at theta = 0.0 between D8S264 and D8S1287, spanning approximately 30 cM (about 12.7 megabases). The GATA4 gene (600576) was found to be in the interval.
Molecular Genetics
In a 5-generation pedigree segregating autosomal dominant congenital heart defects, with all affected individuals manifesting ASD, Garg et al. (2003) identified a gly296-to-ser mutation in the GATA4 gene (G296S; 600576.0001). All affected individuals who were clinically evaluated had the G296S mutation, suggesting complete penetrance of the disease phenotype. Garg et al. (2003) identified a second family with autosomal dominant transmission of atrial septal defects in which mutation of GATA4 (600576.0002) was found in all available affected family members spanning 4 generations.
In affected members of 2 families with isolated ASD, Hirayama-Yamada et al. (2005) found 2 mutations in the GATA4 gene: in 1 family they identified a 1075delG mutation (600576.0002), and in the other they identified an S52F mutation (600576.0003).
Tomita-Mitchell et al. (2007) identified 4 missense sequence variants in the GATA4 gene (see, e.g., 600576.0004; 600576.0005) in 5 of 628 patients with cardiac septal or conotruncal defects. One patient had tetralogy of Fallot (187500). The findings indicated that GATA4 mutations are uncommon in patients with septal defects.
In an affected father, 2 sons, and grandson from a 3-generation Chinese family segregating autosomal dominant atrial septal defect and pulmonary stenosis, Chen et al. (2010) identified heterozygosity for a missense mutation in GATA4 (600576.0016) that was not found in unaffected family members or in 800 healthy controls. Analysis of GATA4 in 30 additional patients with nonsyndromic congenital heart defects, including 10 with ASD, 10 with VSD, 8 with VSD combined with ASD, and 2 with AVSD, did not reveal any mutations.
In 4 affected sisters and 4 affected offspring from a Chinese family with secundum ASD, Chen et al. (2010) identified heterozygosity for a missense mutation in GATA4 (600576.0017). The sisters' unaffected father carried the mutation, which was not found in other unaffected family members, 100 healthy controls, or 70 sporadic patients with congenital heart disease, including 20 with ASD. Three of the 8 affected family members also had pulmonary stenosis.
INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Atrial septal defect \- Pulmonary valve thickening or stenosis \- Ventricular septal defect (in some patients) \- Atrioventricular septal defect (in some patients) \- Cardiac valve insufficiency (in some patients) MOLECULAR BASIS \- Caused by mutation in the GATA-binding protein-4 gene (GATA4, 600576.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
ATRIAL SEPTAL DEFECT 2
|
c0018817
| 7,358 |
omim
|
https://www.omim.org/entry/607941
| 2019-09-22T16:08:30 |
{"doid": ["0110107"], "mesh": ["D006344"], "omim": ["607941"], "orphanet": ["1478"]}
|
Heart rate that is below the normal range
Bradycardia
Other namesBradyarrhythmia, brachycardia
Sinus bradycardia seen in lead II with a heart rate of about 50BPM
Pronunciation
* /ˌbrædɪˈkɑːrdiə/
SpecialtyCardiology
Frequency15% (males), 7% (females)
Bradycardia is a condition typically defined wherein an individual has a resting heart rate of under 60 beats per minute (BPM) in adults, although some studies use a heart rate of less than 50 BPM.[1] Bradycardia typically does not cause symptoms until the rate drops below 50 BPM. When symptomatic, it may cause fatigue, weakness, dizziness, sweating, and at very low rates, fainting.[2]
During sleep, a slow heartbeat with rates around 40–50 BPM is common, and is considered normal. Highly trained athletes may also have athletic heart syndrome, a very slow resting heart rate that occurs as a sport adaptation and helps prevent tachycardia during training.[3]
The term "relative bradycardia" is used to refer to a heart rate that, although not actually below 60 BPM, is still considered too slow for the individual's current medical condition.
The word "bradycardia" is from the Greek βραδύς bradys "slow", and καρδία kardia "heart".[4]
## Contents
* 1 Classification
* 1.1 Sinus
* 1.2 Atrioventricular junction
* 1.3 Ventricular
* 1.4 Infantile
* 2 Causes
* 3 Diagnosis
* 4 Management
* 4.1 Stable
* 4.2 Unstable
* 5 Epidemiology
* 6 Society and culture
* 6.1 Records
* 7 See also
* 8 References
* 9 External links
## Classification[edit]
Illustration comparing the EKGs of a healthy person (top) and a person with bradycardia (bottom): The points on the heart where the EKG signals are measured are also shown.
### Sinus[edit]
Atrial bradycardias are divided into three types. The first, respiratory sinus arrhythmia, is usually found in young and healthy adults. Heart rate increases during inhalation and decreases during exhalation. This is thought to be caused by changes in the vagal tone during respiration.[5] If the decrease during exhalation drops the heart rate below 60 BPM on each breath, this type of bradycardia is usually deemed benign and a sign of good autonomic tone.
The second, sinus bradycardia, is a sinus rhythm of less than 60 BPM. It is a common condition found in both healthy individuals and those considered well-conditioned athletes. Studies have found that 50–85% of conditioned athletes have benign sinus bradycardia, as compared to 23% of the general population studied.[6] The heart muscle of athletes has become conditioned to have a higher stroke volume, so requires fewer contractions to circulate the same volume of blood.[5]
The third, sick sinus syndrome, covers conditions that include severe sinus bradycardia, sinoatrial block, sinus arrest, and bradycardia-tachycardia syndrome (atrial fibrillation, atrial flutter, and paroxysmal supraventricular tachycardia).[5]
### Atrioventricular junction[edit]
An AV-junctional rhythm, or atrioventricular nodal bradycardia, is usually caused by the absence of the electrical impulse from the sinus node. This usually appears on an electrocardiogram (EKG) with a normal QRS complex accompanied with an inverted P wave either before, during, or after the QRS complex.[5]
An AV-junctional escape beat is a delayed heartbeat originating from an ectopic focus somewhere in the AV junction. It occurs when the rate of depolarization of the SA node falls below the rate of the AV node.[5] This dysrhythmia also may occur when the electrical impulses from the SA node fail to reach the AV node because of SA or AV block.[7] This is a protective mechanism for the heart, to compensate for an SA node that is no longer handling the pacemaking activity, and is one of a series of backup sites that can take over pacemaker function when the SA node fails to do so. This would present with a longer PR interval. An AV-junctional escape complex is a normal response that may result from excessive vagal tone on the SA node. Pathological causes include sinus bradycardia, sinus arrest, sinus exit block, or AV block.[5]
### Ventricular[edit]
Idioventricular rhythm, also known as atrioventricular bradycardia or ventricular escape rhythm, is a heart rate of less than 50 BPM. This is a safety mechanism when a lack of electrical impulse or stimuli from the atrium occurs.[5] Impulses originating within or below the bundle of His in the AV node will produce a wide QRS complex with heart rates between 20 and 40 BPM. Those above the bundle of His, also known as junctional, will typically range between 40 and 60 BPM with a narrow QRS complex.[8][9] In a third-degree heart block, about 61% take place at the bundle branch-Purkinje system, 21% at the AV node, and 15% at the bundle of His.[9] AV block may be ruled out with an EKG indicating "a 1:1 relationship between P waves and QRS complexes."[8] Ventricular bradycardias occurs with sinus bradycardia, sinus arrest, and AV block. Treatment often consists of the administration of atropine and cardiac pacing.[5]
### Infantile[edit]
For infants, bradycardia is defined as a heart rate less than 100 BPM (normal is around 120–160 BPM) . Premature babies are more likely than full-term babies to have apnea and bradycardia spells; their cause is not clearly understood. The spells may be related to centers inside the brain that regulate breathing which may not be fully developed. Touching the baby gently or rocking the incubator slightly will almost always get the baby to start breathing again, which increases the heart rate. Medications (theophylline or caffeine) can be used to treat these spells in babies if necessary. Neonatal intensive-care unit (NICU) standard practice is to electronically monitor the heart and lungs for this reason.
## Causes[edit]
This arrhythmia can be underlain by several causes, which are best divided into cardiac and non-cardiac causes. Non-cardiac causes are usually secondary, and can involve recreational drug use or abuse; metabolic or endocrine issues, especially hypothyroidism; an electrolyte imbalance; neurologic factors; autonomic reflexes; situational factors such as prolonged bed rest; and autoimmunity.[10]
Cardiac causes include acute or chronic ischemic heart disease, vascular heart disease, valvular heart disease, or degenerative primary electrical disease. Ultimately, the causes act by three mechanisms: depressed automaticity of the heart, conduction block, or escape pacemakers and rhythms.
In general, two types of problems result in bradycardias: disorders of the SA node, and disorders of the AV node.
With SA node dysfunction (sometimes called sick sinus syndrome), there may be disordered automaticity or impaired conduction of the impulse from the SA node into the surrounding atrial tissue (an "exit block"). Second-degree sinoatrial blocks can be detected only by use of a 12-lead EKG.[11] It is difficult and sometimes impossible to assign a mechanism to any particular bradycardia, but the underlying mechanism is not clinically relevant to treatment, which is the same in both cases of sick sinus syndrome: a permanent pacemaker.
AV conduction disturbances (AV block; primary AV block, secondary type I AV block, secondary type II AV block, tertiary AV block) may result from impaired conduction in the AV node, or anywhere below it, such as in the bundle of His. The clinical relevance pertaining to AV blocks is greater than that of SA blocks.[11]
Beta blocker medicines also can slow the heart rate and decrease how forcefully the heart contracts. Beta blockers may slow the heart rate to a dangerous level if prescribed with calcium channel blocker-type medications.
Bradycardia is also part of the mammalian diving reflex.[12]
## Diagnosis[edit]
A diagnosis of bradycardia in adults is based on a heart rate less than 60 BPM, although some studies use a heart rate of less than 50 BPM.[13] This is determined usually either by palpation or EKG. If symptoms occur, a determination of electrolytes may be helpful in determining the underlying cause.
## Management[edit]
The treatment of bradycardia is dependent on whether or not the person is stable or unstable.[13] If oxygen saturations are low, supplemental oxygen should be provided.
### Stable[edit]
Emergency treatment is not needed if the person is asymptomatic or minimally symptomatic.[13]
### Unstable[edit]
If a person is unstable, the initial recommended treatment is intravenous atropine.[13] Doses less than 0.5 mg should not be used, as this may further decrease the rate.[13] If this is not effective, intravenous inotrope infusion (dopamine, epinephrine) or transcutaneous pacing should be used.[13] Transvenous pacing may be required if the cause of the bradycardia is not rapidly reversible.[13]
In children, giving oxygen, supporting their breathing, and chest compressions are recommended.[14][15]
## Epidemiology[edit]
This section needs expansion with: discussion regarding the threshold of 60 bpm. You can help by adding to it. (December 2018)
The US Centers for Disease Control and Prevention reported in 2011 that 15.2% of adult males and 6.9% of adult females had clinically-defined bradycardia (a resting pulse rate below 60 BPM).[16]
## Society and culture[edit]
### Records[edit]
* Daniel Green holds the world record for the slowest heartbeat in a healthy human, with a heart rate measured in 2014 of 26 BPM.[17]
* Martin Brady holds the Guinness world record for the slowest heart rate with a certified rate over a minute duration of 27 BPM.[18]
* Professional cyclist Miguel Indurain had, during his career, a resting heart rate of 28 BPM.[19]
## See also[edit]
* Bezold–Jarisch reflex
## References[edit]
1. ^ "Types of Arrhythmia". 1 July 2011. Archived from the original on 7 June 2015. Retrieved 19 March 2015.
2. ^ Sinus Bradycardia – eMedicine
3. ^ Baggish, Aaron L.; Wood, Malissa J. (14 June 2011). "Athlete's heart and cardiovascular care of the athlete: scientific and clinical update". Circulation. 123 (23): 2723–2735. doi:10.1161/CIRCULATIONAHA.110.981571. ISSN 1524-4539. PMID 21670241.
4. ^ Prutchi, David (2005). Design and Development of Medical Electronic Instrumentation. John Wiley & Sons. p. 371. ISBN 9780471681830.
5. ^ a b c d e f g h Allan B. Wolfson, ed. (2005). Harwood-Nuss' Clinical Practice of Emergency Medicine (4th ed.). p. 260. ISBN 978-0-7817-5125-4.
6. ^ Ward, Bryan G.; Rippe, J.M. (1992). "11". Athletic Heart Syndrome. Clinical Sports Medicine. p. 259.
7. ^ "AV Junctional Rhythm Disturbances (for Professionals)". American Heart Association. 4 December 2008. Retrieved 15 December 2009.
8. ^ a b "Arrhythmias and Conduction Disorders". The merck Manuals: Online Medical Library. Merck Sharp and Dohme Corp. January 2008. Retrieved 16 December 2009.
9. ^ a b Adams MG, Pelter MM (September 2003). "Ventricular escape rhythms". American Journal of Critical Care. 12 (5): 477–8. doi:10.4037/ajcc2003.12.5.477. PMID 14503433.
10. ^ Ye, Fan; Hatahet, Mohamad; Youniss, Mohamed A.; Toklu, Hale Z.; Mazza, Joseph J.; Yale, Steven (June 2018). "The Clinical Significance of Relative Bradycardia". WMJ. 117 (2): 73–78. ISSN 1098-1861. PMID 30048576.
11. ^ a b Ufberg, JW; Clark, JS (February 2006). "Bradydysrhythmias and atrioventricular conduction blocks". Emerg. Med. Clin. North Am. 24 (1): 1–9, v. doi:10.1016/j.emc.2005.08.006. PMID 16308110.
12. ^ Michael Panneton, W. (2013). "The Mammalian Diving Response: An Enigmatic Reflex to Preserve Life?". Physiology. 28 (5): 284–297. doi:10.1152/physiol.00020.2013. ISSN 1548-9213. PMC 3768097. PMID 23997188.
13. ^ a b c d e f g Neumar RW, Otto CW, Link MS, et al. (November 2010). "Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care". Circulation. 122 (18 Suppl 3): S729–67. doi:10.1161/CIRCULATIONAHA.110.970988. PMID 20956224.
14. ^ de Caen, AR; Berg, MD; Chameides, L; Gooden, CK; Hickey, RW; Scott, HF; Sutton, RM; Tijssen, JA; Topjian, A; van der Jagt, ÉW; Schexnayder, SM; Samson, RA (3 November 2015). "Part 12: Pediatric Advanced Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care". Circulation. 132 (18 Suppl 2): S526–42. doi:10.1161/cir.0000000000000266. PMC 6191296. PMID 26473000.
15. ^ Atkins, DL; Berger, S; Duff, JP; Gonzales, JC; Hunt, EA; Joyner, BL; Meaney, PA; Niles, DE; Samson, RA; Schexnayder, SM (3 November 2015). "Part 11: Pediatric Basic Life Support and Cardiopulmonary Resuscitation Quality: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care". Circulation. 132 (18 Suppl 2): S519–25. doi:10.1161/cir.0000000000000265. PMID 26472999.
16. ^ Yechiam Ostchega; et al. (24 August 2011). "Resting Pulse Rate Reference Data for Children, Adolescents, and Adults: United States, 1999–2008" (PDF). National Health Statistics Reports. Centers for Disease Control. Retrieved 15 December 2018.
17. ^ "Slowest heart rate: Daniel Green breaks Guinness World Records record". World Record Academy. 29 November 2014. Retrieved 5 August 2015.
18. ^ "Lowest heart rate". Guinness World Records. Retrieved 5 August 2015.
19. ^ Lovgren, Stefan (20 August 2004). "Olympic Gold Begins With Good Genes, Experts Say". National Geographic News. Retrieved 8 September 2014.
## External links[edit]
Classification
D
* ICD-10: R00.1
* ICD-9-CM: 427.81, 659.7, 785.9, 779.81
* MeSH: D001919
External resources
* Patient UK: Bradycardia
* v
* t
* e
Cardiovascular disease (heart)
Ischaemic
Coronary disease
* Coronary artery disease (CAD)
* Coronary artery aneurysm
* Spontaneous coronary artery dissection (SCAD)
* Coronary thrombosis
* Coronary vasospasm
* Myocardial bridge
Active ischemia
* Angina pectoris
* Prinzmetal's angina
* Stable angina
* Acute coronary syndrome
* Myocardial infarction
* Unstable angina
Sequelae
* hours
* Hibernating myocardium
* Myocardial stunning
* days
* Myocardial rupture
* weeks
* Aneurysm of heart / Ventricular aneurysm
* Dressler syndrome
Layers
Pericardium
* Pericarditis
* Acute
* Chronic / Constrictive
* Pericardial effusion
* Cardiac tamponade
* Hemopericardium
Myocardium
* Myocarditis
* Chagas disease
* Cardiomyopathy
* Dilated
* Alcoholic
* Hypertrophic
* Tachycardia-induced
* Restrictive
* Loeffler endocarditis
* Cardiac amyloidosis
* Endocardial fibroelastosis
* Arrhythmogenic right ventricular dysplasia
Endocardium /
valves
Endocarditis
* infective endocarditis
* Subacute bacterial endocarditis
* non-infective endocarditis
* Libman–Sacks endocarditis
* Nonbacterial thrombotic endocarditis
Valves
* mitral
* regurgitation
* prolapse
* stenosis
* aortic
* stenosis
* insufficiency
* tricuspid
* stenosis
* insufficiency
* pulmonary
* stenosis
* insufficiency
Conduction /
arrhythmia
Bradycardia
* Sinus bradycardia
* Sick sinus syndrome
* Heart block: Sinoatrial
* AV
* 1°
* 2°
* 3°
* Intraventricular
* Bundle branch block
* Right
* Left
* Left anterior fascicle
* Left posterior fascicle
* Bifascicular
* Trifascicular
* Adams–Stokes syndrome
Tachycardia
(paroxysmal and sinus)
Supraventricular
* Atrial
* Multifocal
* Junctional
* AV nodal reentrant
* Junctional ectopic
Ventricular
* Accelerated idioventricular rhythm
* Catecholaminergic polymorphic
* Torsades de pointes
Premature contraction
* Atrial
* Junctional
* Ventricular
Pre-excitation syndrome
* Lown–Ganong–Levine
* Wolff–Parkinson–White
Flutter / fibrillation
* Atrial flutter
* Ventricular flutter
* Atrial fibrillation
* Familial
* Ventricular fibrillation
Pacemaker
* Ectopic pacemaker / Ectopic beat
* Multifocal atrial tachycardia
* Pacemaker syndrome
* Parasystole
* Wandering atrial pacemaker
Long QT syndrome
* Andersen–Tawil
* Jervell and Lange-Nielsen
* Romano–Ward
Cardiac arrest
* Sudden cardiac death
* Asystole
* Pulseless electrical activity
* Sinoatrial arrest
Other / ungrouped
* hexaxial reference system
* Right axis deviation
* Left axis deviation
* QT
* Short QT syndrome
* T
* T wave alternans
* ST
* Osborn wave
* ST elevation
* ST depression
* Strain pattern
Cardiomegaly
* Ventricular hypertrophy
* Left
* Right / Cor pulmonale
* Atrial enlargement
* Left
* Right
* Athletic heart syndrome
Other
* Cardiac fibrosis
* Heart failure
* Diastolic heart failure
* Cardiac asthma
* Rheumatic fever
* v
* t
* e
Symptoms and signs relating to the circulatory system
Chest pain
* Referred pain
* Angina
* Levine's sign
Auscultation
* Heart sounds
* Split S2
* S3
* S4
* Gallop rhythm
* Heart murmur
* Systolic
* Functional murmur
* Still's murmur
* Diastolic
* Pulmonary insufficiency
* Graham Steell murmur
* Continuous
* Carey Coombs murmur
* Mitral insufficiency
* Presystolic murmur
* Pericardial friction rub
* Heart click
* Bruit
* carotid
Pulse
* Tachycardia
* Bradycardia
* Pulsus paradoxus
* doubled
* Pulsus bisferiens
* Pulsus bigeminus
* Pulsus alternans
Other
* Palpitations
* Apex beat
* Cœur en sabot
* Jugular venous pressure
* Cannon A waves
* Hyperaemia
*
Shock
* Cardiogenic
* Obstructive
* Hypovolemic
* Distributive
* See further Template:Shock
Cardiovascular disease
Aortic insufficiency
* Collapsing pulse
* De Musset's sign
* Duroziez's sign
* Müller's sign
* Austin Flint murmur
* Mayne's sign
Other endocardium
* endocarditis: Roth's spot
* Janeway lesion/Osler's node
* Bracht–Wachter bodies
Pericardium
* Cardiac tamponade/Pericardial effusion: Beck's triad
* Ewart's sign
Other
* rheumatic fever:
* Anitschkow cell
* Aschoff body
* EKG
* J wave
* Gallavardin phenomenon
Vascular disease
Arterial
* aortic aneurysm
* Cardarelli's sign
* Oliver's sign
* pulmonary embolism
* Right heart strain
* radial artery sufficiency
* Allen's test
* pseudohypertension
* thrombus
* Lines of Zahn
* Adson's sign
* arteriovenous fistula
* Nicoladoni sign
Venous
* Friedreich's sign
* Caput medusae
* Kussmaul's sign
* Trendelenburg test
* superior vena cava syndrome
* Pemberton's sign
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Bradycardia
|
c0428977
| 7,359 |
wikipedia
|
https://en.wikipedia.org/wiki/Bradycardia
| 2021-01-18T19:10:58 |
{"mesh": ["D001919"], "umls": ["C0428977"], "icd-9": ["427.81", "659.7", "779.81", "785.9"], "wikidata": ["Q217111"]}
|
A number sign (#) is used with this entry because of evidence that renal hypomagnesemia-2 (HOMG2) is caused by heterozygous mutation in the FXYD2 gene (601814) on chromosome 11q23.
For a discussion of genetic heterogeneity of renal hypomagnesemia, see 602014.
Clinical Features
Geven et al. (1987) reported 2 unrelated families in which hypomagnesemia due to renal magnesium loss was inherited as an autosomal dominant trait. Magnesium infusions performed in 2 patients showed not only a reduced renal magnesium threshold but also a lowered renal tubular maximum for magnesium. All hypomagnesemic members of the family also had a lowered urinary excretion of calcium, presumably as a consequence of increased reabsorption in the loop of Henle. Male-to-male transmission was observed in both families.
De Baaij et al. (2015) studied 2 families segregating autosomal dominant isolated hypomagnesemia. In the first family, hypokalemia and hypomagnesemia were discovered in a 34-year-old Dutch man who presented with pulmonary embolism. He reported a long history of muscle cramps and fatigue, as well as increased fluid intake. His deceased parents had shown no relevant symptoms apart from increased fluid intake in his father. His 9-year-old daughter and 7-year-old son were examined because of muscle cramps, and were found to have hypomagnesemia with hypermagnesuria and hypocalciuria. Both children had a normal growth pattern, normal blood pressure, no dysmorphic features, and unremarkable renal ultrasound and hand x-ray. In the second family, the proband was a 67-year-old Belgian man in whom hypomagnesemia and hypokalemia were found during an episode of tetanic cramps at age 44 years. Examination revealed hypertension, chondrocalcinosis, and renal failure, with hypomagnesemia, hypermagnesuria, and hypocalciuria. His mother was also affected, with chronic fatigue and joint problems for which she took Mg(2+) supplements. The proband's 41-year-old daughter was diagnosed in young adulthood with hypomagnesemia and hypokalemia, and her 16-year-old daughter, who had 2 episodes of seizures, was also found to be affected. Both the daughter and granddaughter had normal renal function apart from hypermagnesuria and hypocalciuria. Symptoms in affected family members included chronic fatigue, generalized weakness, dysesthesias of the face and hands, and frequent cramps of the lower extremities.
Mapping
In the 2 Dutch families described by Geven et al. (1987), Meij et al. (1999) performed a genomewide linkage study. They excluded a possible candidate region on chromosome 9q that encompassed the gene for intestinal hypomagnesemia with secondary hypocalcemia (602014), which maps to 9q12. They then demonstrated linkage to a marker on 11q23 (maximum lod = 6.41 at theta = 0). Detailed haplotype analyses identified a common haplotype segregating in the 2 families, suggesting both their relationship through a common ancestor and the existence of a single, hypomagnesemia-causing mutation in the families.
Heterogeneity
Kantorovich et al. (2002) reported an American family with renal hypomagnesemia without linkage to the 11q23 locus. In testing 22 individuals in the pedigree, multipoint lod scores for 5 different loci from the 11q23 region were equal to -2.97. Compared with unaffected family members and normal controls, affected family members harbored significant reductions in the serum and lymphocyte Mg concentrations and in the serum immunoreactive parathyroid hormone (PTH; 168450) level with a 4-fold increase in the mean fractional urinary Mg excretion rate during a normomagnesemic clamp. The authors concluded that their data demonstrate locus heterogeneity for the phenotype of isolated renal Mg wasting with hypomagnesemia and suggest that hypomagnesemia, at least in this pedigree, may be associated with low bone mass.
Meij et al. (2003) analyzed the FXYD2, CLDN16 (603959), and SLC12A3 (600968) genes in a father and daughter with renal hypomagnesemia and hypocalciuria, but found no mutations. The authors concluded that at least 1 additional gene must be involved in renal magnesium handling.
Molecular Genetics
Meij et al. (2000) screened the FXYD2 gene in affected members of a large Dutch kindred with autosomal dominant hypomagnesemia originally described by Geven et al. (1987) and identified a putative dominant-negative heterozygous mutation (G41R; 601814.0001) that cosegregated with the disorder in 3 different branches of the family and was absent from 132 control chromosomes. The mutation occurred within the putative transmembrane domain of the protein. The authors investigated 2 individuals with an 11q23.3-qter deletion including FXYD2. Both had normal serum magnesium ion levels, showing that rather than haploinsufficiency, the presence of mutant gamma subunit causes hypomagnesemia, consistent with a dominant-negative mechanism. Studies in insect cells showed that whereas the wildtype gamma subunit localized predominantly to the plasma membrane, the mutant protein accumulated in the cytoplasm. A routing defect in transfected COS-1 cells was also observed. This was said to have been the first example of mutations in a gene encoding an Na+,K(+)-ATPase gamma subunit to be implicated in human disease.
In affected members of a Dutch family and a Belgian family segregating autosomal dominant isolated hypomagnesemia, who were negative for mutation in the SLC12A3, HNF1B (189907), and CLCNKB (602023) genes, de Baaij et al. (2015) identified heterozygosity for the G41R mutation in the FXYD2 gene. Patients from both families as well as the Dutch kindred originally reported by Geven et al. (1987) shared the same haplotype, suggesting that all 3 families are related through a common ancestor.
INHERITANCE \- Autosomal dominant GENITOURINARY Kidneys \- Renal magnesium wasting \- Decreased renal calcium excretion \- Renal failure (rare) MUSCLE, SOFT TISSUES \- Muscle cramping, especially of legs \- Generalized weakness \- Chondrocalcinosis NEUROLOGIC Central Nervous System \- Dysesthesias of face and hands \- Seizures LABORATORY ABNORMALITIES \- Hypomagnesemia \- Normal parathyroid hormone \- Hypokalemia \- Hypermagnesuria \- Hypocalciuria MOLECULAR BASIS \- Caused by mutation in the FXYD domain-containing ion transport regulator 2 gene (FXYD2, 601814.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
HYPOMAGNESEMIA 2, RENAL
|
c1835171
| 7,360 |
omim
|
https://www.omim.org/entry/154020
| 2019-09-22T16:38:43 |
{"doid": ["0060885"], "mesh": ["C537152"], "omim": ["154020"], "orphanet": ["34528"], "synonyms": ["Alternative titles", "MAGNESIUM WASTING, RENAL", "MAGNESIUM LOSS, ISOLATED RENAL"]}
|
Jaffe–Campanacci syndrome
Other namesMultiple non-ossifying fibromatosis[1]
Jaffe-Campanacci-Syndrome, boy 7 Y, tibial bowing and cortical/subcortial mixed sclerosis
Jaffe–Campanacci syndrome is one of the disorders associated with café au lait macules (CALMs). Presentations may include intellectual disability, disseminated non-ossifying fibromas of the long bones and jaw, hypogonadism or cryptorchidism, or giant cell granulomas of the jaw.[2]
It was characterized in 1958 and 1983.[3][4][5]
## See also[edit]
* List of cutaneous conditions
## References[edit]
1. ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Multiple non ossifying fibromatosis". www.orpha.net. Retrieved 20 April 2019.
2. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. p. 831. ISBN 978-1-4160-2999-1.
3. ^ synd/2486 at Who Named It?
4. ^ H. L. Jaffe.Non-ossifying fibromata. In: H. L. Jaffe, editor: Tumors and Tumorous Conditions of the Bones and Joints. Philadelphia, Lea & Febiger, 1958, pp 117-141.
5. ^ Campanacci M, Laus M, Boriani S (November 1983). "Multiple non-ossifying fibromata with extraskeletal anomalies: a new syndrome?". J Bone Joint Surg Br. 65 (5): 627–32. doi:10.1302/0301-620X.65B5.6643569. PMID 6643569.[permanent dead link]
## External links[edit]
Classification
D
* ICD-10: M89.2
* DiseasesDB: 32263
External resources
* Orphanet: 2029
This cutaneous condition article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Jaffe–Campanacci syndrome
|
c0796000
| 7,361 |
wikipedia
|
https://en.wikipedia.org/wiki/Jaffe%E2%80%93Campanacci_syndrome
| 2021-01-18T18:49:50 |
{"gard": ["309"], "umls": ["C0796000"], "orphanet": ["2029"], "wikidata": ["Q6121943"]}
|
A rare developmental defect during embryogenesis with digit duplication, polydactyly, syndactyly, and/or hyperphalangy characterized by multiple congenital anomaly syndrome.
## Epidemiology
The precise estimates of birth prevalence are difficult to determine, as ascertainment is erratic (estimated range 1-9/1,000,000).
## Clinical description
The primary findings include widely spaced eyes, macrocephaly with frontal bossing, and pre- or post-axial polydactyly and cutaneous syndactyly. The polydactyly is most commonly preaxial in the feet and postaxial in the hands, with variable cutaneous syndactyly, but the limb findings vary significantly. Other low frequency findings include central nervous system (CNS) anomalies, hernias, and cognitive impairment.
## Etiology
GCPS is caused by loss of function on chromosome 7p14.1 in the transcription factor gene GLI3.
## Diagnostic methods
Clinical diagnosis is challenging because the findings of GCPS are relatively non-specific, and no specific and sensitive clinical criteria have been delineated. A presumptive diagnosis of GCPS can be made if the patient has the classic triad of preaxial polydactyly with cutaneous syndactyly of at least one limb, hypertelorism, and macrocephaly. Individuals with a phenotype consistent with GCPS (but which may not manifest all three attributes listed above) and a GLI3 pathogenic variant may be diagnosed definitively with GCPS. In addition, individuals with a GCPS-consistent phenotype who are related to a definitively diagnosed family member in a pattern consistent with autosomal dominant inheritance may also be diagnosed definitively.
## Differential diagnosis
Differential diagnoses include preaxial polydactyly type 4, the GCPS contiguous gene syndrome, acrocallosal syndrome, Gorlin syndrome, Carpenter syndrome, and Teebi syndrome. The disorder is allelic to Pallister-Hall syndrome and one form of the acrocallosal syndrome.
## Antenatal diagnosis
Antenatal molecular diagnosis is technically feasible.
## Genetic counseling
The disorder is inherited in an autosomal dominant manner. Genetic counseling should be proposed to individuals having the disease-causing mutation informing them that there is 50% risk of passing the pathogenic variant to offspring.
## Management and treatment
Treatment of the disorder is symptomatic, with plastic or orthopedic surgery indicated for significant limb malformations.
## Prognosis
The prognosis for is generally excellent. There may be a slight increase in the incidence of developmental delay or cognitive impairment. Patients with large deletions that include GLI3 may have a poorer prognosis.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Greig cephalopolysyndactyly syndrome
|
c0265306
| 7,362 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=380
| 2021-01-23T18:58:24 |
{"gard": ["6550"], "mesh": ["C537300"], "omim": ["175700"], "umls": ["C0265306"], "icd-10": ["Q87.0"], "synonyms": ["GCPS"]}
|
Ptosis - upper ocular movement limitation - absence of lacrimal punctum is a recently described association of absence of the lower lid lacrimal punctum, bilateral ptosis, elevation deficiency of both eyes and mild facial dysmorphism.
## Epidemiology
It has been described in three siblings.
## Clinical description
The facial dysmorphism includes a narrow and squared forehead, low set and dysplastic ears, a relatively long philtrum, telecanthus, bilateral thick eyebrows and absence of bilateral lower medial eyelashes. The affected patients have no intellectual deficit.
## Genetic counseling
The condition seems to be transmitted as an autosomal recessive trait.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Ptosis-upper ocular movement limitation-absence of lacrimal punctum syndrome
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None
| 7,363 |
orphanet
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https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=228396
| 2021-01-23T16:54:03 |
{"icd-10": ["Q87.0"]}
|
This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed.
Find sources: "Fibrocartilage callus" – news · newspapers · books · scholar · JSTOR (June 2019)
Comminuted midshaft humerus fracture with callus formation.
A fibrocartilage callus is a temporary formation of fibroblasts and chondroblasts which forms at the area of a bone fracture as the bone attempts to heal itself. The cells eventually dissipate and become dormant, lying in the resulting extracellular matrix that is the new bone. The callus is the first sign of union visible on x-rays, usually 3 weeks after the fracture. Callus formation is slower in adults than in children, and in cortical bones than in cancellous bones.[1]
## See also[edit]
* Bone healing
## References[edit]
1. ^ Mirhadi, Sara; Ashwood, Neil; Karagkevrekis, Babis (2013). "Factors influencing fracture healing". Trauma. 15 (2): 140–155. CiteSeerX 10.1.1.834.3328. doi:10.1177/1460408613486571. S2CID 73325632.
* Morgan, Elise F., et al. “Overview of Skeletal Repair (Fracture Healing and Its Assessment).” Methods in Molecular Biology Skeletal Development and Repair, 2014, pp. 13–31. doi:10.1007/978-1-62703-989-5_2
## External links[edit]
* Bony+callus at the US National Library of Medicine Medical Subject Headings (MeSH)
* v
* t
* e
Bone and cartilage
Cartilage
* perichondrium
* fibrocartilage callus
* metaphysis
* Cells
* chondroblast
* chondrocyte
* Types
* hyaline
* elastic
* fibrous
Bone
Ossification
* primary bone
* intramembranous
* endochondral
Cells
* osteoblast
* osteocyte
* osteoclast
Matrix
* bone mineral
* ossein
* osteoid
Types
* cancellous
* cortical
Regions
* subchondral bone
* epiphysis
* epiphyseal plate/metaphysis
* diaphysis
* condyle
* epicondyle
Structure
* osteon
* Haversian canals
* Volkmann's canals
* connective tissue
* endosteum
* periosteum
* Sharpey's fibres
* enthesis
* lacunae
* canaliculi
* trabeculae
* medullary cavity
* bone marrow
Shapes
* long
* short
* flat
* irregular
* sesamoid
This human musculoskeletal system article is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Fibrocartilage callus
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None
| 7,364 |
wikipedia
|
https://en.wikipedia.org/wiki/Fibrocartilage_callus
| 2021-01-18T18:36:26 |
{"mesh": ["D002146"], "wikidata": ["Q1388855"]}
|
Primary familial and congenital polycythemia (PFCP) is an inherited blood disease that causes uncontrolled production of red blood cells (erythrocytes). This leads to an increased volume of red blood cells compared to the total blood volume (erythrocytosis). It may also lead to increased total blood volume or increased blood thickness (hyperviscosity), both of which can cause symptoms. The disease is present at birth, but symptoms (if they develop) may arise any time during childhood or adulthood. Possible symptoms may include headaches, dizziness, fatigue, nosebleeds, difficulty breathing after physical activity, muscle pain, a reddish complexion, and altered mental status. Some people develop blood clots that can block various blood vessels, preventing adequate blood flow (thromboembolic events). Most people have mild symptoms, but some people experience life-threatening complications such as heart attack or stroke. The risk of thrombosis and severe complications increases with age.
PFCP is diagnosed by blood tests detecting isolated erythrocytosis and low EPO levels, in the absence of spleen abnormalities and other underlying diseases that can cause erythrocytosis (such as certain blood diseases and blood cancers).
PFCP is inherited in an autosomal dominant manner, but some people with PFCP have no relatives with the disease. In about 12-15% of people with PFCP, it is caused by mutations in the EPOR gene. However in most people, the genetic cause is not yet known.
Most people with PFCP do not need ongoing treatment. Some people with high blood volume need to have blood drawn periodically (phlebotomy) to treat symptoms or to maintain close-to-normal hematocrit levels. Some people with PFCP need medicines to lower blood pressure (antihypertensive therapy).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Primary familial and congenital polycythemia
|
c0152264
| 7,365 |
gard
|
https://rarediseases.info.nih.gov/diseases/9843/primary-familial-and-congenital-polycythemia
| 2021-01-18T17:58:11 |
{"omim": ["133100"], "orphanet": ["90042"], "synonyms": ["Familial erythrocytosis", "Primary congenital erythrocytosis", "Familial erythrocytosis type 1", "ECYT1", "Polycythemia, primary familial and congenital", "PFCP", "Erythrocytosis autosomal dominant benign", "Congenital polycythemia due to erythropoietin receptor mutation", "Congenital erythrocytosis due to erythropoietin receptor mutation", "Autosomal dominant familial erythrocytosis-1", "Familial erythrocytosis 1", "Primary familial polycythemia"]}
|
A number sign (#) is used with this entry because Usher syndrome type IB (USH1B) is caused by homozygous or compound heterozygous mutation in the MYO7A gene (276903) on chromosome 11q13.
Description
Usher syndrome type I is an autosomal recessive condition characterized by profound congenital hearing impairment with unintelligible speech, early retinitis pigmentosa (usually evident within the first decade), and constant vestibular dysfunction. Type I is distinguished from type II (276901) on the basis of severity of hearing loss and the extent of vestibular involvement. Type I patients are profoundly deaf, whereas type II patients are 'hard of hearing.' Vestibular function is defective in type I patients, whereas type II patients have normal vestibular function (Moller et al., 1989). Patients with type III (USH3; 276902) have progressive hearing loss. Patients with type IV (USH4; 618144) have late onset of both retinitis pigmentosa and progressive, moderate to severe sensorineural hearing loss without vestibular involvement (Khateb et al., 2018).
### Genetic Heterogeneity of Usher Syndrome Type I
USH type I is genetically heterogeneous. USH1C (276904), the 'Acadian variety,' is caused by mutation in harmonin (605242), on 11p15. USH1D (601067) is caused by mutation in the cadherin-23 (CDH23; 605516) on 10q21. USH1F (602083) is caused by mutation in the protocadherin-15 (PCDH15; 605514) on 10q22. USH1G (606943) is caused by mutation in the SANS gene (607696), on 17q25. USH1E (602097) maps to 21q21, and USH1H (612632) maps to 15q22-q23. USH1J (614869) is caused by mutation in the CIB2 gene (605564) on 15q24. USH1K (614990) maps to chromosome 10p11.21-q21.1.
A form of USH type I in which affected members carried heterozygous mutations in both CDH23 and PCDH15 has been reported (USH1D/F; see 601067), thus supporting a digenic model for some individuals with this phenotype.
Gerber et al. (2006) presented evidence that the form of USH1 previously called USH1A, or the 'French variety,' and mapped to chromosome 14 does not in fact exist; mutations in the MYO7A gene were found in most of these families, and in others the phenotype was found to map to other loci.
Ahmed et al. (2003) reviewed the molecular genetics of Usher syndrome and indicated that at least 12 loci had been identified as underlying the 3 different clinical subtypes.
Clinical Features
Usher syndrome, or more appropriately the Usher syndromes, are named for Charles Usher (1914), a British ophthalmologist who emphasized their hereditary nature. The earliest descriptions were given by Von Graefe (1858), Liebreich (1861), who observed the syndrome among Jews in Berlin, and Hammerschlag (1907). Lindenov (1945) wrote on deaf-mutism associated with retinitis pigmentosa and 'feeblemindedness.' Lang (1959) observed 5 affected children out of 10 from a first-cousin marriage. Hallgren (1959) found 177 affected persons in 102 families. In addition to the features noted in the title of his paper, cataract developed by age 40 in most. Mental deficiency and psychosis occurred in about one-quarter of cases. A large majority had a disturbance of gait attributed to a lesion of the labyrinth.
In Finland, Nuutila (1970) found 133 persons with retinitis pigmentosa and congenital sensory deafness, 4 with RP and progressive sensory deafness. Numerous studies suggest genetic heterogeneity of this phenotype. On the basis of 133 patients in Finland, Forsius et al. (1971) concluded that there are 2 distinct forms of the Usher syndrome: one characterized by congenital deafness and severe retinitis pigmentosa, and a second less frequent form in which the inner ear and retina are less severely affected.
Holland et al. (1972) found gyrate atrophy in a few heterozygotes. Davenport et al. (1978) found that about 90% of reported cases had profound congenital deafness with onset of RP before puberty, whereas the rest had moderate to severe hearing loss from birth and RP beginning after puberty. Ataxia, probably labyrinthine in origin, occurred in a great majority of the first type and in a few of the second. The possibility of an X-linked form was suggested by 2 pairs of affected brothers whose mothers were sisters.
Gorlin et al. (1979) summarized the classification of Davenport and Omenn (1977) as follows: type I--profound congenital deafness with onset of RP by age 10; type II--moderate to severe congenital deafness with onset of RP in late teens (276901); type III--RP first noted at puberty with progressive hearing loss; type IV--possible X-linked form. The fourth type was based on the observation of 4 affected brothers reported by Davenport et al. (1978). In fact, autosomal recessive inheritance was considered most likely; the heterozygous parents showed unilateral high-frequency hearing loss with normal retinal and vestibular function.
Jay (1982) found 16 Usher syndrome families out of 571 RP families in the experience of the Moorfields Eye Hospital in London. Other numbers were: autosomal dominant, 130 families; X-linked, 27; autosomal recessive, 5; male multiplex, 24; mixed multiplex, 76; simplex, 292 and adopted, 1. In 4 of 10 sibs, Karjalainen et al. (1983) described an unusual form of Usher syndrome. In 2, hearing loss developed in school age; in the other 2, it developed in the thirties. In 1, retinitis pigmentosa was diagnosed before hearing impairment was evident. In a study of 70 patients, Fishman et al. (1983) also suggested the existence of 2 distinct types of Usher syndrome. In their experience, the deafness is congenital and nonprogressive, whereas the retinitis pigmentosa is progressive. In their type I, onset of night blindness was earlier, visual field loss occurred earlier and in greater severity, hearing impairment was more severe, speech was more likely to be unintelligible, vestibular reflexes and clinically evident ataxia were more frequently found--all as contrasted with type II. Of the 70 patients, 46 were type II.
Boughman et al. (1983) reviewed information on 600 cases of deaf-blindness in the registry of the Helen Keller National Center for Deaf Blind Youths and Adults. Of these, 54% satisfied criteria for the diagnosis of Usher syndrome, although only 23.8% had been so diagnosed. From the Louisiana School for the Deaf, they ascertained 30 males and 18 females in 26 nuclear families, reflecting the recognized high frequency in the Louisiana Acadian population.
Grondahl and Mjoen (1986) found 18 cases of Usher syndrome among 89 probands selected for tapetoretinal degeneration. Among the relatives, another 10 cases of Usher syndrome were found. These fell into the 3 types as follows: type I, 14 cases; type II, 10 cases; type III (according to Davenport and Omenn (1977)), 4 cases. In 12 families the pattern of inheritance was autosomal recessive; the remaining 6 probands were solitary cases without parental consanguinity. There was a high intrafamilial correlation with respect to hearing function. Vestibular response was abolished in 3 patients with type I and was normal in 3 patients with type II and in 1 patient with type III.
In Norway, Grondahl (1987) found 28 patients from 18 families with Usher syndrome. Both retinitis pigmentosa and Usher syndrome were more prevalent in Lapps than in other Norwegians.
Davenport et al. (1988) recognized 2 main types and a third rare type. Type I not only has congenital profound deafness and early onset of RP, but also congenitally absent vestibular function. Their type II has hearing loss which is congenital and of high frequency type, with little deterioration and with later onset of RP and normal vestibular function. In type III both hearing and vision start out normal or near-normal and progressively deteriorate over several decades. Type I children, because of the vestibular defect, have delayed motor milestones and clumsiness. Type II children are usually 'mainstreamed' with no problems until teen age.
Smith et al. (1994) described criteria for the clinical diagnosis of Usher syndrome, adopted by the Usher Syndrome Consortium. They pointed out that there was evidence for at least 3 distinct USH1 loci (USH1A, USH1B, USH1C) and 2 distinct USH2 loci. They pointed to the need to exclude congenital infections, such as rubella, syphilis, and cytomegalovirus, and problems associated with gestation, delivery, or the perinatal period that also can cause profound hearing loss and retinal damage.
Photoreceptors, auditory hair cells, and vestibular hair cells develop from ciliated progenitors. Several lines of evidence suggest that a generalized abnormality of axoneme structure is present in patients with Usher syndrome. Hunter et al. (1986) found a high proportion of abnormal axonemes in retinal photoreceptor cells of a patient with Usher syndrome. Shinkawa and Nadol (1986) found a decrease in outer ciliary cells in the lower part of the cochlea in this syndrome. Structural and functional evidence for abnormal nasal cilia has been found in this disorder as in other patients with retinitis pigmentosa (Arden and Fox, 1979). Finally, sperm motility, velocity, and structure have been found abnormal in Usher syndrome, a feature probably related to the markedly decreased fertility of these patients (Hunter et al., 1986; Nuutila, 1970). Brueckner et al. (1989) found that the iv (inversus viscerum; see 603339) mutation in the mouse maps to a corresponding region; this mouse mutation may be homologous to Kartagener syndrome (244400). Lake and Sharma (1973) reported the association of Kartagener syndrome with retinitis pigmentosa and congenital deafness. Bonneau et al. (1993) reported the association of type I Usher syndrome with bronchiectasis, chronic sinusitis, and reduced nasal mucociliary clearance in 2 brothers and suggested that USH1 could be a primary ciliary disorder.
Schaefer et al. (1998) performed quantitative analysis of magnetic resonance imaging studies of 19 patients with Usher syndrome (8 with type I, 11 with type II). They found a significant decrease in intracranial volume and in size of the brain and cerebellum with a trend toward an increase in the size of the subarachnoid spaces. These data suggested that the disease process in Usher syndrome involves the entire brain and is not limited to the posterior fossa or auditory and visual systems.
Malm et al. (2011) evaluated visual function, comprising both the severity of the rod cone degeneration and the function in the macular region, in 12 patients genotyped as Usher syndrome 1B, 1D, 1F, 2A, 2C, or 3A, including 3 families with affected sibs, and confirmed phenotypic heterogeneity between sibs with the same genotype and between patients with different genotypes. In all patients examined with ERG, the 30 Hz flicker response revealed remaining cone function. In 3 of the patients with Usher type I, multifocal electroretinography (mfERG) demonstrated a specific pattern with a sharp distinction between the area of reduced function and the central area with remaining macular function and normal peak time. Optical coherence tomography (OCT) demonstrated loss of foveal depression with distortion of the foveal architecture in the macula of all patients. The foveal thickness ranged from 159 to 384 micrometers and was not correlated with retinal function.
Inheritance
Usher syndrome is inherited in an autosomal recessive manner. In an extensive genetic study of 9 Usher syndrome genes in 172 patients with Usher syndrome due to various genetic defects, Le Quesne Stabej et al. (2012) found no evidence for digenic inheritance. Mutations in the MYO7A gene were the most common, accounting for 53.2% of families.
Population Genetics
The frequency of Usher syndrome was estimated to be 3.0/100,000 in Scandinavia (Hallgren, 1959) and 4.4/100,000 in the United States (Boughman et al., 1983). Grondahl (1987) calculated the prevalence of Usher syndrome in Norway to be 3.6 in 100,000. In Colombia, Tamayo et al. (1991) found that about 70% of the Usher syndrome cases were type I, about 26% type II, and 4% type III.
Weil et al. (1995) stated that USH1B accounts for about 75% of type I Usher syndrome patients.
In 6 (42.86%) of 14 indigenous South African probands with USH, Roberts et al. (2015) identified a homozygous mutation (c.6377delC) in the MYO7A gene. All 6 shared a common haplotype.
Mapping
Kimberling et al. (1992) mapped a form of Usher syndrome to 11q, probably distal to marker D11S527. Their study was based on 27 families from the United States, Sweden, Ireland, and South Africa. There were no families from either the Louisiana Acadian population or the Poitou-Charentes region of France.
Smith et al. (1992) investigated 11 British USH1 families and confirmed linkage to D11S527 at 11q. The locus for Best disease (153700) also maps to 11q3. In an extensive Samaritan kindred in Israel, Bonne-Tamir et al. (1994) demonstrated linkage of the Usher syndrome phenotype to markers on 11q. Complete linkage disequilibrium between D11S533 and the Usher gene suggested that these loci are either identical or adjacent.
Wagenaar et al. (1995) studied 17 obligate carriers from 9 families with autosomal recessive Usher syndrome type I. Linkage studies showed linkage to 11q13.5 in 6 families, while 3 families failed to show linkage to candidate regions. Eight obligate carriers had an abnormal pure-tone audiogram. Four carriers had significant sensorineural hearing loss which increased at higher frequencies. The other 13 carriers had sensorineural hearing loss of about 10 dB at 0.25 and 0.5 kHz, but less at higher frequencies. Electrooculography demonstrated a significantly lower mean light peak/dark trough ratio in carriers than in controls. The methods were, however, not sufficiently specific to identify carriers with confidence.
Molecular Genetics
Weil et al. (1995) demonstrated that mutation in the gene encoding myosin VIIA is responsible for Usher syndrome type IB. Two different premature stop codons, a 6-bp deletion, and 2 missense mutations were detected in 5 unrelated families (see, e.g., 276903.0001-276903.0005). In 1 of these families, the mutations were identified in both alleles. These mutations, which are located at the amino-terminal end of the motor domain of the protein, are likely to result in the absence of a functional protein.
Zina et al. (2001) reevaluated a large consanguineous family from Tunisia, originally reported by Guilford et al. (1994) to have autosomal recessive sensorineural deafness (600060) and in which Weil et al. (1997) identified homozygosity for a missense mutation in the MYO7A gene (276903.0010). Since the original reports, 5 patients had developed mild retinal degeneration in addition to the progressive deafness. Fundus examination of 1 patient showed spicule pigmentary changes consistent with retinal dystrophy. Another previously unaffected family member, homozygous for the mutation, had retinitis pigmentosa. Seven patients had abnormal vestibular function as assessed by caloric tests. Zina et al. (2001) concluded that some patients in this Tunisian family had features consistent with Usher syndrome type IB, and suggested that other factors must modulate the expression of the phenotype.
Adato et al. (1999) described a complex rearrangement of the MYO7A gene that might have a synergistic effect on the symptoms of another type of Usher syndrome, namely USH3 (276902), the rarest form of USH. Adato et al. (1997) reported a nonconsanguineous family of Jewish Yemenite origin with 2 affected and 6 healthy sibs, in which the 2 affected brothers had different USH phenotypes: one had a typical USH1 phenotype, whereas the other had a typical USH3 phenotype. Both affected brothers had onset of bilateral progressive pigmentary retinopathy during early adolescence. Adato et al. (1999) performed haplotype segregation and linkage analysis in this family that resulted in exclusion of all USH1 and USH2 loci and suggested linkage only to the USH3 locus on chromosome 3q21; both affected brothers were homozygous for alleles of 4 markers on 3q. Since one of the affected brothers had a USH1 phenotype, family members were screened for mutations in the MYO7A gene, and 2 novel, closely situated nucleotide changes were detected in exon 25 of the MYO7A gene on 1 maternal chromosome: a T-to-C transition and a guanine deletion 5 nucleotides upstream of this transition (276903.0014). The mutated MYO7A gene was carried by the brother with the more severe USH1 phenotype, but not by his affected brother with the USH3 phenotype. The mother and 2 unaffected sibs, who were all double heterozygotes for the mutated MYO7A and for a single USH3 haplotype, showed no evidence of any Usher symptoms or nonsyndromic deafness. This suggested a digenic inheritance pattern, with a possible synergistic interaction between MYO7A and the USH3 gene product, where presence of a single defective MYO7A allele seemed to increase the severity of deafness as a part of the clinical symptoms associated with USH3. Adato et al. (2002) restudied the Jewish Yemenite family originally reported by Adato et al. (1997) and identified homozygosity for a 23-bp deletion in the CLRN1 gene (606397.0007) in the affected brothers. The authors stated that this represented a departure from the monogenic model for Usher syndrome.
In a 4-year follow-up of their diagnostic service in France for patients with Usher syndrome type I, which included preliminary haplotyping before gene sequencing, Roux et al. (2011) stated that they had identified the pathogenic genotype in over 90% of patients. Of the mutations identified, 32% were novel.
History
### Usher Syndrome Type IA
In an intriguing 'chronicle of a slow death,' Gerber et al. (2006) concluded that the presumed USH1A locus on 14q32 does not exist. The USH1A locus was described by Kaplan et al. (1992) and Larget-Piet et al. (1994) on the basis of linkage studies in 9 families originating from the Poitou-Charentes region, around the town of Bressuire in France. This form of Usher syndrome was also referred to as the French variety. No disease-associated alteration was found in any candidate gene candidate gene at the USH1A locus. Results of studies of a new multiplex family with Usher syndrome type 1 originating from the Bressuire region surprisingly showed exclusion of linkage to chromosome 14 but were compatible with linkage to the USH1B locus on 11q. Furthermore, Gerber et al. (2006) had an opportunity to study a healthy individual in 1 of the 8 original USH1A families who was unavailable for study in 1992; this individual turned out to be haploidentical to his affected sibs, which strongly challenged the existence of the USHA1 locus. These 2 unexpected data prompted a screening for mutations in the major USH1 gene myosin VIIA (MYO7A; 276903) in the Bressuire families. The results of this study 'signed the death warrant of the USH1A locus,' since mutations were identified in 6 of the 9 original families. Of these and the 1 additional family, 7 harbored mutations in the MYO7A gene, 1 was compatible with linkage to USH1D and USH1E loci, and 1 excluded all USH1 loci including the 14q32.1 region. No DNA was available for further linkage studies in the last family.
In the reevaluation, Kaplan and her colleagues (Gerber et al., 2006) suggested that they should not have made the hypothesis of a founder effect in the original study without evidence for linkage disequilibrium. Indeed most of the patients of Bressuire harbored different MYO7A mutations. A parallel was drawn to the case in the isolated Newfoundland population where a high incidence of Bardet-Biedl syndrome (209900) exists. The genetic study of 17 BBS kindreds hailing from this region showed that at least 4 loci might account for the disease (Woods et al., 1999).
Gerber et al. (1996) suggested the existence of a novel form of Usher syndrome type I from the fact that the 3 previously reported loci on chromosomes 14q32, 11q13, and 11p15 were excluded by linkage studies in 2 large multiplex families of Moroccan and Pakistani ancestry.
INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Profound sensorineural hearing loss \- Absent vestibular function (caloric test) Eyes \- Retinitis pigmentosa \- Extinction of electroretinogram (before age 10) \- Visual loss NEUROLOGIC Central Nervous System \- Delayed motor development MISCELLANEOUS \- Known as the 'French variety' of Usher syndrome since the majority of families are from Poitou-Charentes, France \- Genetic heterogeneity \- Usher syndrome type I (congenital profound deafness, absent vestibular function, and prepubertal onset of retinitis pigmentosa) - 7 loci \- User syndrome type II (congenital moderate-severe deafness, normal vestibular dysfunction, and onset of retinitis pigmentosa in late second to early third decade) - 3 loci \- Usher syndrome type III (postlingual progressive deafness, variable vestibular dysfunction, and progressive retinitis pigmentosa with variable age of onset) - 1 locus MOLECULAR BASIS \- Caused by mutation in the myosin VIIA gene (MYO7A, 276903.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
USHER SYNDROME, TYPE I
|
c0271097
| 7,366 |
omim
|
https://www.omim.org/entry/276900
| 2019-09-22T16:21:26 |
{"doid": ["0110826"], "mesh": ["D052245"], "omim": ["276900"], "orphanet": ["886", "231169"], "synonyms": ["Alternative titles", "US1", "RETINITIS PIGMENTOSA AND CONGENITAL DEAFNESS"], "genereviews": ["NBK1265"]}
|
## Description
Asthma-related traits include clinical symptoms of asthma, such as coughing, wheezing, and dyspnea; bronchial hyperresponsiveness (BHR) as assessed by methacholine challenge test; serum IgE levels; atopy; and atopic dermatitis (Laitinen et al., 2001; Illig and Wjst, 2002).
For a general phenotypic description and a discussion of genetic heterogeneity of asthma, see 600807, and of allergic rhinitis, see 607154.
Mapping
By genomewide analysis of 295 French families from the EGEA study with asthma and/or allergic rhinitis, Dizier et al. (2007) found linkage to a locus on chromosome 1p31 (maximum multipoint lod score of 3.05 at marker D1S2890; p = 0.0002 and 0.0016 after Bonferroni correction). The predivided sample test (PST) showed significant heterogeneity of linkage to chromosome 1p31 between the asthma plus allergic rhinitis phenotype and the asthma only or allergic rhinitis only phenotype (PST = 12.5 at marker D1S2890; p = 0.00007 and 0.002 after Bonferroni correction). The findings indicated that comorbidity of asthma and allergic rhinitis represents a phenotypic entity. The authors noted that linkage analysis of atopic asthma did not show any evidence of linkage to chromosome 1p31.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
ASTHMA-RELATED TRAITS, SUSCEPTIBILITY TO, 4
|
c1970474
| 7,367 |
omim
|
https://www.omim.org/entry/610906
| 2019-09-22T16:03:55 |
{"omim": ["610906"], "synonyms": ["Alternative titles", "ASRT4", "ASTHMA AND ALLERGIC RHINITIS, SUSCEPTIBILITY TO"]}
|
A rare, genetic, congenital limb malformation syndrome characterized by a unique combination of bilateral, symmetrical camptodactyly and clinodactyly of 5th fingers, mesoaxial camptodactyly of toes, and ulnar deviation of 3rd fingers. Additional variable manifestations include bifid toes and severe syndactyly, or synpolydactyly, involving all digits of hands and feet.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Syndactyly-camptodactyly and clinodactyly of fifth fingers-bifid toes syndrome
|
c3554611
| 7,368 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=357332
| 2021-01-23T16:54:41 |
{"omim": ["615170"], "icd-10": ["Q87.2"], "synonyms": ["Synactyly-camptodactyly and clinodactyly of fifth fingers-bifid halluces syndrome", "Wahab syndrome"]}
|
Nasopharyngeal angiofibroma
Other namesJuvenile nasopharyngeal angiofibroma[1][2]
Micrograph of a nasopharyngeal angiofibroma H&E stain.
SpecialtyENT surgery
Nasopharyngeal angiofibroma, also known as juvenile nasal angiofibroma, is a histologically benign but locally aggressive vascular tumor of the nasopharynx that arises from the superior margin of the sphenopalatine foramen and grows in the back of the nasal cavity. It most commonly affects adolescent males (because it is a hormone-sensitive tumor). Though it is a benign tumor, it is locally invasive and can invade the nose, cheek, orbit (frog face deformity), or brain.[3] Patients with nasopharyngeal angiofibroma usually present with one-sided nasal obstruction with profuse epistaxis.
## Contents
* 1 Signs and symptoms
* 2 Diagnosis
* 2.1 Differential diagnosis
* 3 Staging
* 4 Treatment
* 5 Prognosis
* 6 References
* 7 External links
## Signs and symptoms[edit]
* Frequent chronic epistaxis or blood-tinged nasal discharge
* Nasal obstruction and rhinorrhea
* Facial dysmorphism (when locally invasive)
* Conductive hearing loss from eustachian-tube obstruction
* Diplopia, which occurs secondary to erosion into superior orbital fissure and due to third and sixth nerve palsy.
* Proptosis when having intraorbital extension.
* Rarely anosmia, recurrent otitis media, and eye pain.
## Diagnosis[edit]
If nasopharyngeal angiofibroma is suspected based on physical examination (a smooth vascular submucosal mass in the posterior nasal cavity of an adolescent male), imaging studies such as CT or MRI should be performed. Biopsy should be avoided as to avoid extensive bleeding since the tumor is composed of blood vessels without a muscular coat.[citation needed]
Antral sign or Holman-Miller sign (forward bowing of posterior wall of maxilla) is pathognomic of angiofibroma.[citation needed]
DSA (digital subtraction angiography) of carotid artery to see the extension of tumors and feeding vessels[citation needed]
### Differential diagnosis[edit]
* Antro-choanal polyp (benign non neoplastic growth)[4]
* Rhinosporidiosis (as bleeding point is here too)
* Malignancy—nasopharyngeal carcinoma, lymphoma, plasmacytoma, rhabdomyosarcoma
* Chordoma
* Nasopharyngeal cyst
* Pyogenic granuloma
## Staging[edit]
Thera are many different staging- systems published.[5] One of the most used is that of Radkowsky:[6]
Stage Tumor Extension
IA Limited to the nose or the nasopharynx
IB Extension into one or more paranasal sinus
IIA Minimal extension through sphenopalatine foramen into and including a minimal part of the medial-most part of pterygomaxillary fossa
IIB Full involvement of the pterygomaxillary fossa, displacing posterior wall of maxillary antrum forward. Lateral or anterior displacement of the branches of maxillary artery. Superior extension may occur, eroding the orbital bones
IIC Extension through the pterygomaxillary fossa into the cheek and temporal fossa or posterior to the pterygoid plates
IIIA Erosion of the skull base with minimal intracranial extension
IIIB Erosion of skull base with extensive intracranial involvement with or without cavernous sinus involvement
## Treatment[edit]
Treatment for Nasopharyngeal angiofibroma (JNA) is primarily surgical. The tumor is primarily excised by external or endoscopic approach. Medical treatment and radiation therapy are only of historical interest.[citation needed]
External approaches:[citation needed]
* transpalatine approach
* transpalatine + sublabial (Sardana's) Approach
* infratemporal Approach
* nasal endoscopic Approach
* transmaxillary Approach
* maxillary swing Approach or Facial translocation
Endoscopic approach is an excellent tool in primary and recurrent JNA, it allows visualisation and precise removal of the lesion. Preoperative embolisation of tumour may be of some use in reducing intraoperative bleeding.[citation needed]
Direct visualization is not common-[citation needed]
1. If the tumor is limited to nasopharynx and nose, for endoscopic approach or Wilson's transpalatal approach is used. It can be extended into Sardana's approach if the tumor extends laterally.
2. For tumors of infratemporal fossa, Maxillary Swing approach is used.
3. Transmaxillary Le Fort 1 approach is used for tumors extending into maxillary and ethmoid sinuses and pterygopalatine fossa.
4. If the tumor extend up to the cheek, for Weber–Ferguson approach should be used.
## Prognosis[edit]
Prognosis for nasopharyngeal angiofibroma is favorable. Because these tumors are benign, metastasis to distal sites does not occur. However, these tumors are highly vascularized and grow rapidly. Removal is important in preventing nasal obstruction and recurrent epistaxis. Mortality is not associated with nasopharyngeal angiofibroma.[7]
## References[edit]
1. ^ 00021 at CHORUS
2. ^ "juvenile nasopharyngeal angiofibroma" at Dorland's Medical Dictionary
3. ^ Raphael Rubin; David S. Strayer; Emanuel Rubin (2008). Rubin's Pathology: clinicopathologic foundations of medicine. Lippincott Williams & Wilkins. pp. 1071–. ISBN 978-0-7817-9516-6. Retrieved 29 June 2010.
4. ^ Tos, Mirko; Larsen, Per L.; Larsen, Knud; Cayé-Thomasen, Per (2000), Stamm, Aldo Cassol; Draf, Wolfgang (eds.), "Nasal Polyps", Micro-endoscopic Surgery of the Paranasal Sinuses and the Skull Base, Springer Berlin Heidelberg, pp. 103–125, doi:10.1007/978-3-642-57153-4_8, ISBN 9783642571534
5. ^ Alshaikh, Nada Ali; Eleftheriadou, Anna (2015). "Juvenile nasopharyngeal angiofibroma staging: An overview". Ear, Nose, & Throat Journal. 94 (6): E12–22. doi:10.1177/014556131509400615. ISSN 1942-7522. PMID 26053985.
6. ^ Radkowski, D.; McGill, T.; Healy, G. B.; Ohlms, L.; Jones, D. T. (1996). "Angiofibroma. Changes in staging and treatment". Archives of Otolaryngology--Head & Neck Surgery. 122 (2): 122–129. doi:10.1001/archotol.1996.01890140012004. ISSN 0886-4470. PMID 8630204.
7. ^ Textbook of Family Medicine, 8th Edition. Chapter 19 p.329. Rakel, MD. ISBN 978-1-4377-1160-8
## External links[edit]
Classification
D
* DiseasesDB: 32229
External resources
* MedlinePlus: 001572
* eMedicine: ent/470
* v
* t
* e
Cancer involving the respiratory tract
Upper RT
Nasal cavity
Esthesioneuroblastoma
Nasopharynx
Nasopharyngeal carcinoma
Nasopharyngeal angiofibroma
Larynx
Laryngeal cancer
Laryngeal papillomatosis
Lower RT
Trachea
* Tracheal tumor
Lung
Non-small-cell lung carcinoma
* Squamous-cell carcinoma
* Adenocarcinoma (Mucinous cystadenocarcinoma)
* Large-cell lung carcinoma
* Rhabdoid carcinoma
* Sarcomatoid carcinoma
* Carcinoid
* Salivary gland–like carcinoma
* Adenosquamous carcinoma
* Papillary adenocarcinoma
* Giant-cell carcinoma
Small-cell carcinoma
* Combined small-cell carcinoma
Non-carcinoma
* Sarcoma
* Lymphoma
* Immature teratoma
* Melanoma
By location
* Pancoast tumor
* Solitary pulmonary nodule
* Central lung
* Peripheral lung
* Bronchial leiomyoma
Pleura
* Mesothelioma
* Malignant solitary fibrous tumor
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Nasopharyngeal angiofibroma
|
c1367536
| 7,369 |
wikipedia
|
https://en.wikipedia.org/wiki/Nasopharyngeal_angiofibroma
| 2021-01-18T18:28:39 |
{"umls": ["C1367536"], "orphanet": ["289596"], "wikidata": ["Q546357"]}
|
Condensing osteitis
Other namesfocal sclerosing osteomyelitis
SpecialtyDentistry
Condensing osteitis is a periapical inflammatory disease that results from a reaction to a dental related infection. This causes more bone production rather than bone destruction in the area (most common site is near the root apices of premolars and molars). The lesion appears as a radiopacity in the periapical area hence the sclerotic reaction. The sclerotic reaction results from good patient immunity and a low degree of virulence of the offending bacteria. The associated tooth may be carious or contains a large restoration, and is usually associated with a non-vital tooth. It was described by Dr. Carl Garré in 1893.
## Contents
* 1 Cause
* 2 Diagnosis
* 2.1 Differential diagnosis
* 3 Treatment
* 4 Prognosis
* 5 References
* 6 External links
## Cause[edit]
Infection of periapical tissues of a high immunity host by organisms of low virulence which leads to a localized bony reaction to a low grade inflammatory stimulus.
## Diagnosis[edit]
* 1- TENDERNESS ON VERTICAL PERCUSSION.
This section is empty. You can help by adding to it. (December 2017)
### Differential diagnosis[edit]
* 1- Idiopathic osteosclerosis.
* 2- cementoblastoma.
* NOTE: An abnormal result with pulp testing strongly suggests condensing osteitis and tends to rule out osteosclerosis and cementoblastoma.
## Treatment[edit]
The process is usually asymptomatic and benign, in most cases the tooth will require root canal treatment. endodontic treatment.
The offending tooth should be tested for vitality of the pulp, if inflamed or necrotic, then endodontic treatment is required as soon as possible, while hopeless teeth should be extracted.
## Prognosis[edit]
The prognosis is excellent, once root canal treatment is completed. If the offending tooth is extracted, the area of condensing osteitis may remain in the jaws indefinitely, which is termed osteosclerosis or bone scar.
## References[edit]
## External links[edit]
Classification
D
* DiseasesDB: 33858
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Condensing osteitis
|
c0152263
| 7,370 |
wikipedia
|
https://en.wikipedia.org/wiki/Condensing_osteitis
| 2021-01-18T19:04:54 |
{"icd-9": ["733.5"], "icd-10": ["M85.3"], "wikidata": ["Q5159188"]}
|
Hyperoxaluria
Other namesBird's disease
Oxalate
SpecialtyEndocrinology
Hyperoxaluria is an excessive urinary excretion of oxalate. Individuals with hyperoxaluria often have calcium oxalate kidney stones. It is sometimes called Bird's disease, after Golding Bird, who first described the condition.
## Contents
* 1 Causes
* 2 Diagnosis
* 2.1 Types
* 3 Treatment
* 4 Controversy
* 5 References
* 6 External links
## Causes[edit]
Hyperoxaluria can be primary (as a result of a genetic defect) or secondary to another disease process.
Type I primary hyperoxaluria (PH1) is associated mutations in the gene encoding AGXT, a key enzyme involved in oxalate metabolism. PH1 is an example of a protein mistargeting disease, wherein AGXT shows a trafficking defect. Instead of being trafficked to peroxisomes, it is targeted to mitochondria, where it is metabolically deficient despite being catalytically active. Type II is associated with GRHPR.[1]
Secondary hyperoxaluria can occur as a complication of jejunoileal bypass, or in a patient who has lost much of the ileum with an intact colon. In these cases, hyperoxaluria is caused by excessive gastrointestinal oxalate absorption.[2]
Excessive intake of oxalate-containing food, such as rhubarb, may also be a cause in rare cases.[3]
## Diagnosis[edit]
### Types[edit]
* Primary hyperoxaluria
* Enteric hyperoxaluria
* Idiopathic hyperoxaluria
* Oxalate poisoning
## Treatment[edit]
The main therapeutic approach to primary hyperoxaluria is still restricted to symptomatic treatment, i.e. kidney transplantation once the disease has already reached mature or terminal stages. However, through genomics and proteomics approaches, efforts are currently being made to elucidate the kinetics of AGXT folding which has a direct bearing on its targeting to appropriate subcellular localization. Secondary hyperoxaluria is much more common than primary hyperoxaluria, and should be treated by limiting dietary oxalate and providing calcium supplementation. A child with primary hyperoxaluria was treated with a liver and kidney transplant.[4] A favorable outcome is more likely if a kidney transplant is complemented by a liver transplant, given the disease originates in the liver.
## Controversy[edit]
Perhaps the key difficulty in understanding pathogenesis of primary hyperoxaluria, or more specifically, why AGXT ends up in mitochondria instead of peroxisomes, stems from AGXT's somewhat peculiar evolution. Namely, prior to its current peroxysomal 'destiny', AGXT indeed used to be bound to mitochondria. AGXT's peroxisomal targeting sequence is uniquely specific for mammalian species, suggesting the presence of additional peroxisomal targeting information elsewhere in the AGT molecule. As AGXT was redirected to peroxisomes over the course of evolution, it is plausible that its current aberrant localization to mitochondria owes to some hidden molecular signature in AGXT's spatial configuration unmasked by PH1 mutations affecting the AGXT gene.
## References[edit]
1. ^ "Primary hyperoxaluria - Genetics Home Reference".
2. ^ Surgery PreTest Self-Assessment and Review, Twelfth Edition
3. ^ Marc Albersmeyer; Robert Hilge; Angelika Schröttle; Max Weiss; Thomas Sitter; Volker Vielhauer (30 October 2012). "Acute kidney injury after ingestion of rhubarb: secondary oxalate nephropathy in a patient with type 1 diabetes". BMC Nephrology. 13: 141. doi:10.1186/1471-2369-13-141. ISSN 1471-2369. PMC 3504561. PMID 23110375. Wikidata Q34461274.
4. ^ "India News & Business - MSN India: News, Business, Finance, Sports, Politics & more. - News". Archived from the original on 2007-09-29. Retrieved 2007-05-09.
## External links[edit]
Classification
D
* ICD-10: E74.8
* ICD-9-CM: 271.8
* MeSH: D006959
* DiseasesDB: 31642
External resources
* eMedicine: med/3027
* Patient UK: Hyperoxaluria
* GeneReviews/NIH/NCBI/UW entry on Primary Hyperoxaluria Type 1
* v
* t
* e
Inborn error of carbohydrate metabolism: monosaccharide metabolism disorders
Including glycogen storage diseases (GSD)
Sucrose, transport
(extracellular)
Disaccharide catabolism
* Congenital alactasia
* Sucrose intolerance
Monosaccharide transport
* Glucose-galactose malabsorption
* Inborn errors of renal tubular transport (Renal glycosuria)
* Fructose malabsorption
Hexose → glucose
Monosaccharide catabolism
Fructose:
* Essential fructosuria
* Fructose intolerance
Galactose / galactosemia:
* GALK deficiency
* GALT deficiency/GALE deficiency
Glucose ⇄ glycogen
Glycogenesis
* GSD type 0 (glycogen synthase deficiency)
* GSD type IV (Andersen's disease, branching enzyme deficiency)
* Adult polyglucosan body disease (APBD)
Glycogenolysis
Extralysosomal:
* GSD type III (Cori's disease, debranching enzyme deficiency)
* GSD type VI (Hers' disease, liver glycogen phosphorylase deficiency)
* GSD type V (McArdle's disease, myophosphorylase deficiency)
* GSD type IX (phosphorylase kinase deficiency)
Lysosomal (LSD):
* GSD type II (Pompe's disease, glucosidase deficiency)
Glucose ⇄ CAC
Glycolysis
* MODY 2/HHF3
* GSD type VII (Tarui's disease, phosphofructokinase deficiency)
* Triosephosphate isomerase deficiency
* Pyruvate kinase deficiency
Gluconeogenesis
* PCD
* Fructose bisphosphatase deficiency
* GSD type I (von Gierke's disease, glucose 6-phosphatase deficiency)
Pentose phosphate pathway
* Glucose-6-phosphate dehydrogenase deficiency
* Transaldolase deficiency
* 6-phosphogluconate dehydrogenase deficiency
Other
* Hyperoxaluria
* Primary hyperoxaluria
* Pentosuria
* Aldolase A deficiency
* v
* t
* e
Components and results of urine tests
Components
* Albumin
* Myoglobin
* hCG
* Leukocyte esterase
* Urine pregnancy test
* Ketone bodies
* Glucose
* Urobilinogen
* Bilirubin
* Creatinine
* RBC
* WBC
* Urinary casts
Chemical properties
* Urine specific gravity
* Isosthenuria
* Urine osmolality
* Hypersthenuria
* Urine pH
* Urine anion gap
Abnormal findings
Red blood cells
* Hematuria (Microscopic hematuria)
White blood cells
* Eosinophiluria
Proteinuria
* Albuminuria/Microalbuminuria
* Albumin/creatinine ratio
* Urine protein/creatinine ratio
* Myoglobinuria
* Hemoglobinuria
* Bence Jones protein
Small molecules
* Glycosuria
* Ketonuria
* Bilirubinuria
* Hyperuricosuria
* Aminoaciduria
Other
* Bacteriuria
* Chyluria
* Crystalluria
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Hyperoxaluria
|
c0020500
| 7,371 |
wikipedia
|
https://en.wikipedia.org/wiki/Hyperoxaluria
| 2021-01-18T18:51:23 |
{"mesh": ["D006959"], "icd-9": ["271.8"], "icd-10": ["E74.8"], "wikidata": ["Q1641060"]}
|
Allan–Herndon–Dudley syndrome
This condition is inherited in an X-linked recessive manner
SpecialtyMedical genetics, neurology, pediatrics
Allan–Herndon–Dudley syndrome is a rare X-linked inherited disorder of brain development that causes both moderate to severe intellectual disability and problems with speech and movement.[1]
Allan–Herndon–Dudley syndrome, which is named eponymously for William Allan, Florence C. Dudley, and C. Nash Herndon,[2][3] results from a mutation of the thyroid hormone transporter MCT8 (also referred to as SLC16A2). Consequently, thyroid hormones are unable to enter the nervous system, which depends on thyroid signaling for proper function and development.[citation needed]
## Contents
* 1 Signs and symptoms
* 2 Genetics
* 3 Pathogenesis
* 4 Diagnosis
* 5 Treatment
* 6 References
* 7 External links
## Signs and symptoms[edit]
It is estimated that 80–99% of people with Allan-Herndon-Dudley syndrome will have biparietal narrowing (narrowing of skull), ataxia, abnormalities of the neck, and both absent speech development and aphasia. Weak muscle tone (hypotonia) and underdevelopment of many muscles (muscle hypoplasia) are common in children with Allan-Herndon-Dudley syndrome. Development of joint deformities called contractures, which restrict the movement of certain joints, are common as people age. Mobility is further limited by abnormal muscle stiffness (spasticity), muscle weakness, and involuntary movements of the arms and legs. Many people with Allan–Herndon–Dudley syndrome are unable to walk independently and become wheelchair-bound by adulthood.[4]
## Genetics[edit]
This condition is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.[citation needed]
In X-linked recessive inheritance, a female with one altered copy of the gene in each cell is called a carrier. She can pass on the mutated gene, but usually does not experience signs and symptoms of the disorder. Carriers of SLC16A2 mutations have normal intelligence and do not experience problems with movement. Some carriers have been diagnosed with thyroid disease, a condition which is relatively common in the general population. It is unclear whether thyroid disease is related to SLC16A2 mutations in these cases.[citation needed]
## Pathogenesis[edit]
Mutations in the SLC16A2 gene cause Allan–Herndon–Dudley syndrome. The SLC16A2 gene, also known as MCT8, provides instructions for making a protein that plays a critical role in the development of the nervous system. This protein transports a particular hormone into nerve cells in the developing brain. This hormone, called triiodothyronine or T3, is produced by the thyroid. T3 appears to be critical for the normal formation and growth of nerve cells, as well as the development of junctions between nerve cells (synapses) where cell-to-cell communication occurs. T3 and other forms of thyroid hormone also help regulate the development of other organs and control the rate of chemical reactions in the body.[citation needed]
Gene mutations alter the structure and function of the SLC16A2 protein. As a result, this protein is unable to transport T3 into nerve cells effectively. A lack of this critical hormone in certain parts of the brain disrupts normal brain development, resulting in intellectual disability and problems with movement. Excess amounts of T3 circulate in the bloodstream. It is unclear if this is a consequence of compensatory hyperdeiodination or if it results from impaired uptake by certain cell types. Increased T3 levels in the blood may be toxic to some organs and contribute to the signs and symptoms of Allan–Herndon–Dudley syndrome.[citation needed]
## Diagnosis[edit]
This section is empty. You can help by adding to it. (November 2016)
## Treatment[edit]
In May 2013, the US FDA granted Orphan drug status to Diiodothyropropionic acid (DITPA) in the treatment of MCT8 deficiency. This was following the use of DITPA towards a child in Australia, under compassionate grounds.[5]
Theoretical considerations suggested TRIAC (triiodothyroacetate or tiratricol, a natural non-classical thyroid hormone) to be beneficial. In 2014, a case was demonstrated in which therapy with TRIAC in early childhood led to significant improvement of cognition and mobility.[6] A first clinical trial[7] demonstrated TRIAC to be safe and effective.[8]
## References[edit]
1. ^ "Allan-Herndon-Dudley syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2018-04-17.
2. ^ synd/1438 at Who Named It?
3. ^ Allan, William; Herndon, C. N.; Dudley, Florence C. (1944). "Some examples of the inheritance of mental deficiency: apparently sex-linked idiocy and microcephaly". American Journal of Mental Deficiency. 48: 325–34.
4. ^ "Allan-Herndon-Dudley syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2018-04-17.
5. ^ Verge, Charles F.; Konrad, Daniel; Cohen, Michal; Di Cosmo, Caterina; Dumitrescu, Alexandra M.; Marcinkowski, Teresa; Hameed, Shihab; Hamilton, Jill; Weiss, Roy E.; Refetoff, Samuel (2012). "Diiodothyropropionic Acid (DITPA) in the Treatment of MCT8 Deficiency". The Journal of Clinical Endocrinology & Metabolism. 97 (12): 4515–23. doi:10.1210/jc.2012-2556. PMC 3513545. PMID 22993035.
6. ^ Iglesias, Ainhoa; Palomares, María; Morte, Beatriz; Obregón, María Jesús; Bernal, Juan (September 10, 2014). TRIAC treatment of an infant with Allan-Herndon-Dudley Syndrome (AHDS): Effects on iodothyronines in serum and cerebrospinal fluid. 38th Annual Meeting of the European Thyroid Association. Santiago de Compostela. hdl:10261/125597.
7. ^ Clinical trial number NCT02060474 for "Triac Trial in MCT8 Patients" at ClinicalTrials.gov
8. ^ Groeneweg, S; Peeters, RP; Moran, C; Stoupa, A; Auriol, F; Tonduti, D; Dica, A; Paone, L; Rozenkova, K; Malikova, J; van der Walt, A; de Coo, IFM; McGowan, A; Lyons, G; Aarsen, FK; Barca, D; van Beynum, IM; van der Knoop, MM; Jansen, J; Manshande, M; Lunsing, RJ; Nowak, S; den Uil, CA; Zillikens, MC; Visser, FE; Vrijmoeth, P; de Wit, MCY; Wolf, NI; Zandstra, A; Ambegaonkar, G; Singh, Y; de Rijke, YB; Medici, M; Bertini, ES; Depoorter, S; Lebl, J; Cappa, M; De Meirleir, L; Krude, H; Craiu, D; Zibordi, F; Oliver Petit, I; Polak, M; Chatterjee, K; Visser, TJ; Visser, WE (September 2019). "Effectiveness and safety of the tri-iodothyronine analogue Triac in children and adults with MCT8 deficiency: an international, single-arm, open-label, phase 2 trial". The Lancet. Diabetes & Endocrinology. 7 (9): 695–706. doi:10.1016/S2213-8587(19)30155-X. PMID 31377265.
## External links[edit]
Classification
D
* OMIM: 300523
* MeSH: C537047 C537047, C537047
* GeneReviews/NCBI/NIH/UW entry on MCT8 (SLC16A2)-Specific Thyroid Hormone Cell Transporter Deficiency
* Allan–Herndon–Dudley syndrome at National Library of Medicine
* v
* t
* e
Genetic disorder, membrane: Solute carrier disorders
1-10
* SLC1A3
* Episodic ataxia 6
* SLC2A1
* De Vivo disease
* SLC2A5
* Fructose malabsorption
* SLC2A10
* Arterial tortuosity syndrome
* SLC3A1
* Cystinuria
* SLC4A1
* Hereditary spherocytosis 4/Hereditary elliptocytosis 4
* SLC4A11
* Congenital endothelial dystrophy type 2
* Fuchs' dystrophy 4
* SLC5A1
* Glucose-galactose malabsorption
* SLC5A2
* Renal glycosuria
* SLC5A5
* Thyroid dyshormonogenesis type 1
* SLC6A19
* Hartnup disease
* SLC7A7
* Lysinuric protein intolerance
* SLC7A9
* Cystinuria
11-20
* SLC11A1
* Crohn's disease
* SLC12A3
* Gitelman syndrome
* SLC16A1
* HHF7
* SLC16A2
* Allan–Herndon–Dudley syndrome
* SLC17A5
* Salla disease
* SLC17A8
* DFNA25
21-40
* SLC26A2
* Multiple epiphyseal dysplasia 4
* Achondrogenesis type 1B
* Recessive multiple epiphyseal dysplasia
* Atelosteogenesis, type II
* Diastrophic dysplasia
* SLC26A4
* Pendred syndrome
* SLC35C1
* CDOG 2C
* SLC39A4
* Acrodermatitis enteropathica
* SLC40A1
* African iron overload
see also solute carrier family
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Allan–Herndon–Dudley syndrome
|
c0795889
| 7,372 |
wikipedia
|
https://en.wikipedia.org/wiki/Allan%E2%80%93Herndon%E2%80%93Dudley_syndrome
| 2021-01-18T19:05:25 |
{"gard": ["5617"], "mesh": ["C537047"], "umls": ["C0795889"], "orphanet": ["280270", "59"], "wikidata": ["Q4731121"]}
|
## Mapping
In a genomewide scan using 385 microsatellite markers in 1,261 individuals representing 402 nuclear families of African American origin, Li et al. (2006) found a region near marker D10S1432 on chromosome 10q22 that showed significant linkage to indexed smoking quantity, with a maximum lod score of 4.17 at 92 cM. They also found evidence of suggestive linkage on chromosomes 9, 11, and 13 for major genetic determinants of nicotine dependence.
In a genomewide scan of 505 individuals consisting mostly of dizygotic twin pairs from 153 Finnish families ascertained for cigarette smoking, Loukola et al. (2008) found linkage to chromosome 10q25 (maximum 2-point nonparametric lod score of 3.35 at D10S597). Suggestive evidence was also observed for binge drinking at chromosome 10q25 (maximum 2-point lod score of 2.49 at D10S141), overlapping the smoking locus. Loukola et al. (2008) suggested that this may represent the shared genetic etiology for these traits.
The Tobacco and Genetics Consortium (2010) reported the findings of genomewide association studies for number of cigarettes smoked per day among about 74,000 European individuals from multiple different cohorts, including those of Thorgeirsson et al. (2010) and Liu et al. (2010). Significant associations were found for 2 SNPs at chromosome 10q25: the G allele of rs1329650 (p = 5.7 x 10(-10)) and the A allele of rs1028936 (p = 1.3 x 10(-9)). The SNPs are located in a noncoding RNA.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
SMOKING AS A QUANTITATIVE TRAIT LOCUS 1
|
c1970249
| 7,373 |
omim
|
https://www.omim.org/entry/611003
| 2019-09-22T16:03:46 |
{"omim": ["611003"]}
|
## Description
Acquired partial lipodystrophy (APLD) is characterized clinically by the gradual onset of bilaterally symmetrical loss of subcutaneous fat from the face, neck, upper extremities, thorax, and abdomen, in the 'cephalocaudal' sequence, sparing the lower extremities. A large group of patients (83%) with acquired partial lipodystrophy have low serum levels of complement component C3 due to the presence of C3 nephritic factor, an IgG antibody that causes continuous activation of the alternative complement pathway and consumption of serum C3. About 22% of patients with this acquired complement defect develop membranoproliferative glomerulonephritis. Some individuals may also show an increased risk of infection (Misra et al., 2004).
Acquired partial lipodystrophy is not inherited in a classic mendelian pattern; it rather represents a phenotype with a complex etiology. Affected individuals may have genetic susceptibility factors that require the additional presence of environmental factors or acquired disorders to be expressed (summary by Hegele et al., 2006). Most cases are sporadic, family history is negative, and females are more often affected than males (ratio, 4:1) (summary by Misra et al., 2004).
See 608709 for a subtype of APLD not associated with low complement C3 or renal disease.
Clinical Features
Alper et al. (1973) reported a 30-year-old woman with a lifelong history of recurrent bacterial infections who was found to have low serum C3 due to presence in the serum of an activator of C3, which the authors termed hypercatabolism. Since age 4 years, she had progressive loss of subcutaneous fat from the upper part of the body. There was no family history of a similar disorder. Although renal disease was not specifically mentioned, she did have protein and granular casts in the urine on at least 1 occasion. Alper et al. (1973) noted the association between partial lipodystrophy, low C3, and a circulating factor that activated the alternative complement pathway, and suggested that the increased risk of infection was due to continuous depletion of C3.
Sissons et al. (1976) reported 21 unrelated patients with partial lipodystrophy. Laboratory studies showed that 17 had low serum C3, accompanied in 14 by C3 nephritic factor, suggesting activation of the alternative complement pathway. These abnormalities occurred in 10 patients without clinically overt renal disease. However, 7 patients had overt membranoproliferative nephritis. Lipodystrophy preceded the nephritis in all patients. Sissons et al. (1976) concluded that the majority of patients with partial lipodystrophy have hypocomplementemia. Although nephritis may not invariably develop, the high rate of mesangiocapillary nephritis in these patients suggested that complement activation via the alternative pathway predisposes to the development of glomerular disease.
A patient with acquired partial lipodystrophy reported by Kraai and van Son (1983) was the only member of her family to show features. Since the age of 5 years, she had ascetic facial features with loss of facial fat ('facies Voltarien'). At age 20 years, she developed nephrotic syndrome after a throat infection. Kidney biopsy showed membranoproliferative glomerulonephritis, and laboratory values showed decreased serum C3 and C4, as well as proteinuria, hematuria, and leukocyturia.
Misra et al. (2004) reported 35 cases of acquired partial lipodystrophy and reviewed 220 cases reported in the literature. The median age at onset of lipodystrophy was 7 years, and the female to male ratio was 4:1. Approximately 83% of patients had low serum C3 with the presence of the C3 nephritic factor autoantibody. Approximately 22% of patients developed membranoproliferative glomerulonephritis about 8 years after the onset of lipodystrophy. Diabetes mellitus and impaired glucose tolerance were seen in 6.7% and 8.9%, respectively. Activation of the alternative complement pathway was implicated in the cooccurrence of these features.
Inheritance
Acquired partial lipodystrophy is not an inherited disorder in the classic mendelian sense; it rather represents a phenotype with a complex etiology (summary by Hegele et al., 2006).
Reichel et al. (1976) reported identical twins who were discordant for partial lipodystrophy. A 7-year-old girl developed acute glomerulonephritis with proteinuria, hematuria, and lymphocytosis, without edema. Following a tonsillectomy, the patient developed sunken facial features which progressed to loss of subcutaneous fat from the trunk and upper limbs by age 18 years. Proteinuria and erythrocyturia were found, and kidney biopsy showed membranoproliferative glomerulonephritis with focal crescents and complement component C3 deposits along glomerular basement membranes. Serum C3 was approximately one-third of normal values, while C4 was normal. Reichel et al. (1976) noted that the patient had a susceptibility to infection, with a history of pneumonia, meningitis, encephalitis, and viral hepatitis. As her identical twin sister had no symptoms, the authors concluded that the disorder was acquired.
Bier et al. (1978) also reported discordance for cephalothoracic lipodystrophy with hypocomplementemic renal disease in identical twin sisters. Following a tonsillectomy at the age of 5 years, the affected sister was noted to have loss of facial fat with progression to the upper limbs and upper chest. Laboratory findings showed proteinuria, hematuria, and decreased serum C3. Her twin sister had normal clinical features and laboratory findings.
Power et al. (1990) described a family in which 3 members had partial lipodystrophy. Two of the 3, a mother and a son, also had C3 nephritic factor and membranoproliferative glomerulonephritis. Both the mother and the son had end-stage renal disease. Power et al. (1990) stated that the occurrence of these features is usually sporadic, but their family report suggested that the pathogenesis of these conditions may be linked and that genetically determined factors may, in some circumstances, contribute to disease susceptibility.
Pathogenesis
The loss of fat from the waist upward with sparing of the legs in partial lipodystrophy was a mystery until it was discovered that adipose cells are the main source of factor D (134350), which completes the formation of the C3 convertase enzyme (C3bBb) by cleaving factor B bound to C3b (White et al., 1992). There is a gradient in the concentration of factor D in the fat cells of the body; more is present in the upper than in the lower half of the body, which may explain the distribution of the fat loss. It is likely that in patients with partial lipodystrophy with C3 nephritic factor, the antibody stabilizes the C3bBb C3 convertase that forms in the immediate vicinity of adipocytes. The abnormally stabilized enzyme may then cleave enough C3 to allow assembly of the membrane-attack complex, which lyses adipocytes. These reactions and others involved in complement activation were diagrammed by Walport (2001).
INHERITANCE \- Isolated cases HEAD & NECK Face \- Loss of subcutaneous adipose tissue from face \- Sunken face \- 'Progeroid' expression GENITOURINARY Kidneys \- Membranoproliferative glomerulonephritis (26%) \- Nephrotic syndrome MUSCLE, SOFT TISSUES \- Loss of subcutaneous adipose tissue from face, progressive \- Loss of subcutaneous adipose tissue from upper limbs and trunk IMMUNOLOGY \- Frequent infections \- Decreased serum C3 \- Presence of C3 nephritic factor autoantibody LABORATORY ABNORMALITIES \- Hematuria \- Proteinuria MISCELLANEOUS \- Onset in first or second decade \- More common in females (male:female ratio 4:1) \- Variable phenotype \- No family history \- Association with autoimmune diseases ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
LIPODYSTROPHY, PARTIAL, ACQUIRED, WITH LOW COMPLEMENT COMPONENT C3, WITH OR WITHOUT GLOMERULONEPHRITIS
|
c3151347
| 7,374 |
omim
|
https://www.omim.org/entry/613913
| 2019-09-22T15:57:02 |
{"omim": ["613913"], "synonyms": ["Alternative titles", "LIPODYSTROPHY, PARTIAL, ACQUIRED, ASSOCIATED WITH C3 NEPHRITIC FACTOR"]}
|
A number sign (#) is used with this entry because of evidence that familial episodic pain syndrome-1 (FEPS1) is caused by heterozygous mutation in the TRPA1 gene (604775) on chromosome 8q13. One such family has been reported.
Description
Familial episodic pain syndrome-1 is an autosomal dominant neurologic disorder characterized by onset in infancy of episodic debilitating upper body pain triggered by fasting, cold, and physical stress (summary by Kremeyer et al., 2010).
### Genetic Heterogeneity of Familial Episodic Pain Syndrome
See also FEPS2 (615551), caused by mutation in the SCN10A gene (604427) on chromosome 3p22, and FEPS3 (615552), caused by mutation in the SCN11A gene (604385) on chromosome 3p22.
Clinical Features
Kremeyer et al. (2010) reported a large 4-generation family from Colombia, South America, in which 21 individuals had an episodic pain syndrome. The disorder was characterized by onset in infancy of episodic debilitating upper body pain usually triggered by fasting, fatigue, cold, illness, and/or physical exertion. The episodes typically lasted about 1.5 hours, had a prodromal phase during which the episode could sometimes be aborted, and were followed by a period of exhaustion and deep sleep. The episodes of intense pain were accompanied by breathing difficulties, tachycardia, sweating, generalized pallor, peribuccal cyanosis, and stiffness of the abdominal wall. However, affected individuals reported no altered pain sensitivity outside the episodes, and neurologic examination was normal. Skin biopsies of affected individuals showed no abnormalities of intraepidermal nerve fibers, and quantitative sensory testing in affected individuals was similar to unaffected individuals. Tests with mustard oil, known to activate TRPA1 receptors, showed that some affected individuals had higher flare responses and secondary hyperalgesia compared to unaffected individuals.
Inheritance
The transmission pattern of FEPS in the family reported by Kremeyer et al. (2010) was consistent with autosomal dominant inheritance.
Mapping
By linkage and haplotype analysis, Kremeyer et al. (2010) mapped the episodic pain syndrome in a large Colombian family to chromosome 8q12-q13. A maximum multipoint lod score of 5.36 was obtained at 8q13.
Molecular Genetics
By linkage analysis followed by candidate gene sequencing in a large Colombian family with episodic pain syndrome, Kremeyer et al. (2010) identified a heterozygous missense mutation in the TRPA1 gene (N855S; 604775.0001). The mutation completely segregated with the disorder. In vitro functional expression studies indicated that the mutation resulted in a gain of function of channel activity.
INHERITANCE \- Autosomal dominant CARDIOVASCULAR Heart \- Tachycardia during pain episodes RESPIRATORY \- Breathing difficulties during pain episodes SKIN, NAILS, & HAIR Skin \- Enhanced secondary hyperalgesia and flare response on mustard oil application NEUROLOGIC Central Nervous System \- Pain, episodic \- Pain affects upper body MISCELLANEOUS \- Onset in infancy \- Episodes last about 1.5 hours \- Episodes are triggered by hunger, fatigue, cold, stress \- Episodes are followed by exhaustion and sleep \- One family has been reported (last curated January 2013) MOLECULAR BASIS \- Caused by mutation in the transient receptor potential cation channel, subfamily A, member 1 gene (TRPA1, 604775.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
EPISODIC PAIN SYNDROME, FAMILIAL, 1
|
c3808667
| 7,375 |
omim
|
https://www.omim.org/entry/615040
| 2019-09-22T15:53:17 |
{"omim": ["615040"], "orphanet": ["391384", "391389"], "synonyms": ["FEPS"]}
|
## Clinical Features
Meijer et al. (2004) reported a large French Canadian family in which 7 of 14 sibs had a pure form of spastic paraplegia (SPG) with adult onset (25 to 45 years). All affected individuals had moderate to severe lower limb spastic paraparesis with hyperreflexia, extensor plantar responses, and spastic bladders. There was also moderate to severe decrease of vibration sense in the feet. Two individuals had dysarthria. Only 1 patient was wheelchair-bound. Nerve conduction studies showed normal sensory and compound muscle action potentials, but somatosensory-evoked potentials were abnormal in 2 patients studied.
Mapping
Two-point parametric linkage analysis on the family reported by Meijer et al. (2004), under an autosomal recessive model, identified a putative disease locus, designated SPG27, on chromosome 10q22.1-q24.1 (maximum lod score of 4.49 at markers D10S580 and D10S1765). The critical disease locus spans approximately 26 Mb between markers D10S606 and D10S1758 and partially overlaps with the SPG9 (601162) locus. However, the authors noted that SPG9 is autosomal dominant and has additional neurologic features ('complicated').
INHERITANCE \- Autosomal recessive GENITOURINARY Bladder \- Spastic/hyperactive bladder NEUROLOGIC Central Nervous System \- Lower limb spasticity \- Lower limb hyperreflexia \- Extensor plantar responses \- Dysarthria \- Normal muscle strength \- Decreased vibration sense in feet \- Decreased somatosensory-evoked potentials MISCELLANEOUS \- Adult onset (25-45 years) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
SPASTIC PARAPLEGIA 27, AUTOSOMAL RECESSIVE
|
c1836899
| 7,376 |
omim
|
https://www.omim.org/entry/609041
| 2019-09-22T16:06:48 |
{"doid": ["0110778"], "mesh": ["C563807"], "omim": ["609041"], "orphanet": ["101007"]}
|
Tear of the tendon that runs from the quadriceps muscle to the top of the knee cap
This article needs more medical references for verification or relies too heavily on primary sources. Please review the contents of the article and add the appropriate references if you can. Unsourced or poorly sourced material may be challenged and removed.
Find sources: "Quadriceps tendon rupture" – news · newspapers · books · scholar · JSTOR (December 2017)
Quadriceps tendon rupture
Other namesQuadriceps tendon tear
An x-ray demonstrating quadriceps tendon rupture. Note the abnormal angle of the patella and soft-tissue swelling marked by the arrow.
SpecialtyOrthopedic
A quadriceps tendon rupture is a tear of the tendon that runs from the quadriceps muscle to the top of the knee cap.[1]
## Contents
* 1 Signs and symptoms
* 2 Diagnosis
* 3 Treatment
* 4 References
* 5 External links
## Signs and symptoms[edit]
Symptoms are pain and the inability to extend the knee against resistance. A gap can often be palpated at the tendon's normal location.
## Diagnosis[edit]
The diagnosis is usually made clinically, but ultrasound or MRI can be used if there is any doubt.
* Quadriceps tendon rupture in plain X-ray
* Quadriceps tendon rupture in plain X-ray: Incomplete rupture with haematoma in tendon.
* Quadriceps tendon rupture in plain X-ray
* X-ray of a tear of the patellar tendon. On the left: The kneecap is pulled up. On the right: Significant dent in the soft tissue above the kneecap.
* Operative image: 1. Kneecap 2. upper patella pole with drill holes 3. Stump of the quadriceps tendon
## Treatment[edit]
The tendon can be surgically repaired. Afterwards a brace is given that prevents flexion of the knee. Athletes who have suffered this injury generally return to action in about 9 months to a year.
## References[edit]
1. ^ "Quadriceps Tendon Rupture: Practice Essentials, Anatomy, Pathophysiology". 2017-07-19. Cite journal requires `|journal=` (help)
## External links[edit]
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D
* ICD-9-CM: 727.65
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*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Quadriceps tendon rupture
|
c0263968
| 7,377 |
wikipedia
|
https://en.wikipedia.org/wiki/Quadriceps_tendon_rupture
| 2021-01-18T18:42:19 |
{"umls": ["C0263968"], "icd-9": ["727.65"], "wikidata": ["Q769457"]}
|
Uncombable hair syndrome (UHS), or pili trianguli et canaliculi, is a rare scalp hair shaft dysplasia.
## Epidemiology
Prevalence is unknown.
## Clinical description
Onset is usually between ages 3 months and 12 years. Hair becomes progressively silvery-blond or straw-colored, dry and disordered, standing out from the scalp and growing in different directions, and being unmanageable to comb it flat. The quantity of hair stays normal. Microscopic analysis reveals a longitudinal groove of the hair shaft with a triangular or kidney-shaped section. The anomaly is clinically detectable when approximately 50% of hairs are affected. Several conditions have been reported to occur with UHS such as ectodermal dysplasia, retinal dysplasia, retinal pigmentary dystrophy, juvenile cataract, digit abnormalities, tooth enamel anomalies, oligodontia, phalango-epiphyseal dysplasia, alopecia areata, atopic eczema, and ichthyosis vulgaris.
## Etiology
The stiffness and brightness of hair are supposed to result from a misshapen dermal papilla inducing an anomaly in the keratinization of the inner root sheath.
## Diagnostic methods
Diagnosis relies on clinical and microscopic observation, but electron microscopic analysis of hair shaft can eliminate other hair anomalies.
## Differential diagnosis
Differential diagnosis includes Rapp-Hodgkin ectodermal dysplasia, loose anagen hair syndrome, ectrodactyly, cleft/lip palate syndrome, familial tricho-odonto-onchyial ectodermal dysplasia with syndactyly and other ectodermal dysplasias.
## Genetic counseling
UHS is likely to be an autosomal dominant inherited disease with a variable penetrance but no causal gene has been identified yet.
## Management and treatment
UHS spontaneously regresses in late childhood and only gentle care including conditioners, soft brushes and avoidance of harsh treatments cares of the hair are recommended. Biotin treatment as been used in several patients and might be useful to control nail fragility, leading to acclaimed increase in hair growth after 4 months of supplementation.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Uncombable hair syndrome
|
c0432347
| 7,378 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=1410
| 2021-01-23T17:46:24 |
{"gard": ["5404"], "mesh": ["C536939"], "omim": ["191480", "617251", "617252"], "umls": ["C0432347"], "icd-10": ["Q84.1"], "synonyms": ["Pili trianguli et canaliculi"]}
|
Hartnup disease
Other namesAminoaciduria, Hartnup type
Tryptophan
SpecialtyEndocrinology
Hartnup disease has an autosomal recessive pattern of inheritance.
Hartnup disease (also known as "pellagra-like dermatosis"[1] and "Hartnup disorder"[2]) is an autosomal recessive[3] metabolic disorder affecting the absorption of nonpolar amino acids (particularly tryptophan that can be, in turn, converted into serotonin, melatonin, and niacin). Niacin is a precursor to nicotinamide, a necessary component of NAD+.[4]:541
The causative gene, SLC6A19, is located on chromosome 5.[5] It is named after the English family, Hartnup, who suffered from this disease.
## Contents
* 1 Signs and symptoms
* 2 Causes
* 3 Diagnosis
* 4 Treatment
* 5 See also
* 6 References
* 7 External links
## Signs and symptoms[edit]
Hartnup disease manifests during infancy with variable clinical presentation: failure to thrive, photosensitivity, intermittent ataxia, nystagmus, and tremor.[citation needed]
Nicotinamide is necessary for neutral amino acid transporter production in the proximal renal tubules found in the kidney, and intestinal mucosal cells found in the small intestine. Therefore, a symptom stemming from this disorder results in increased amounts of amino acids in the urine. Pellagra, a similar condition, is also caused by low nicotinamide; this disorder results in dermatitis, diarrhea, and dementia.[citation needed]
Hartnup disease is a disorder of amino acid transport in the intestine and kidneys; otherwise, the intestine and kidneys function normally, and the effects of the disease occur mainly in the brain and skin. Symptoms may begin in infancy or early childhood, but sometimes they begin as late as early adulthood. Symptoms may be triggered by sunlight, fever, drugs, or emotional or physical stress. A period of poor nutrition nearly always precedes an attack. The attacks usually become progressively less frequent with age. Most symptoms occur sporadically and are caused by a deficiency of niacinamide. A rash develops on parts of the body exposed to the sun. Mental retardation, short stature, headaches, unsteady gait, and collapsing or fainting are common. Psychiatric problems (such as anxiety, rapid mood changes, delusions, and hallucinations) may also result.[6]
## Causes[edit]
Hartnup disease is inherited as an autosomal recessive trait. Heterozygotes are normal. Consanguinity is common. The failure of amino-acid transport was reported in 1960 from the increased presence of indoles (bacterial metabolites of tryptophan) and tryptophan in the urine of patients as part of a generalized aminoaciduria of the disease. The excessive loss of tryptophan from malabsorption was the cause of the pellagra like symptoms. From studies on ingestion of tryptophan it seemed that there was a generalized problem with amino-acid transport.[7] In 2004, a causative gene, SLC6A19, was located on band 5p15.33. SLC6A19 is a sodium-dependent and chloride-independent neutral amino acid transporter, expressed predominately in the kidneys and intestine.[8]
## Diagnosis[edit]
The defective gene controls the absorption of certain amino acids from the intestine and the reabsorption of those amino acids in the kidneys. Consequently, a person with Hartnup disease cannot absorb amino acids properly from the intestine and cannot reabsorb them properly from tubules in the kidneys. Excessive amounts of amino acids, such as tryptophan, are excreted in the urine. The body is thus left with inadequate amounts of amino acids, which are the building blocks of proteins. With too little tryptophan in the blood, the body is unable to make a sufficient amount of the B-complex vitamin niacinamide, particularly under stress when more vitamins are needed.[6]
In Hartnup disease, urinary excretion of proline, hydroxyproline, and arginine remains unchanged, differentiating it from other causes of generalized aminoaciduria, such as Fanconi syndrome. With urine chromatography, increased levels of neutral amino acids (e.g., glutamine, valine, phenylalanine, leucine, asparagine, citrulline, isoleucine, threonine, alanine, serine, histidine, tyrosine, tryptophan) and indican are found in the urine. Increased urinary Indican can be tested by Obermeyer test.[citation needed]
## Treatment[edit]
A high-protein diet can overcome the deficient transport of neutral amino acids in most patients. Poor nutrition leads to more frequent and more severe attacks of the disease, which is otherwise asymptomatic. All patients who are symptomatic are advised to use physical and chemical protection from sunlight: avoid excessive exposure to sunlight, wear protective clothing, and use chemical sunscreens with a SPF of 15 or greater. Patients also should avoid other aggravating factors, such as photosensitizing drugs, as much as possible. In patients with niacin deficiency and symptomatic disease, daily supplementation with nicotinic acid or nicotinamide reduces both the number and severity of attacks. Neurologic and psychiatric treatment is needed in patients with severe central nervous system involvement.[8]
## See also[edit]
* Citrullinemia
* Cystinosis
* Cystinuria
## References[edit]
1. ^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
2. ^ Online Mendelian Inheritance in Man (OMIM): 234500
3. ^ Kleta R, Romeo E, Ristic Z, Ohura T, Stuart C, Arcos-Burgos M, Dave MH, Wagner CA, Camargo SR, Inoue S, Matsuura N, Helip-Wooley A, Bockenhauer D, Warth R, Bernardini I, Visser G, Eggermann T, Lee P, Chairoungdua A, Jutabha P, Babu E, Nilwarangkoon S, Anzai N, Kanai Y, Verrey F, Gahl WA, Koizumi A (September 2004). "Mutations in SLC6A19, encoding B0AT1, cause Hartnup disorder". Nature Genetics. 36 (9): 999–1002. doi:10.1038/ng1405. PMID 15286787. S2CID 155361.
4. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of the Skin: clinical Dermatology. Saunders Elsevier. ISBN 978-0-7216-2921-6.
5. ^ Seow HF, Brer S, Brer A, Bailey CG, Potter SJ, Cavanaugh JA, Rasko JE (September 2004). "Hartnup disorder is caused by mutations in the gene encoding the neutral amino acid transporter SLC6A19". Nature Genetics. 36 (9): 1003–7. doi:10.1038/ng1406. PMID 15286788.
6. ^ a b LaRosa, CJ (January 2020). "Hartnup Disease". Retrieved 6 July 2020.
7. ^ Milne, M.D., Crawford, M.A., Girao, C.B. and Loughridge, L. (1961) The metabolic disorder of the Hartnup disease. Q. J. Med. 29: 407-421
8. ^ a b Sekulovic, LJ (February 2017). "Hartnup Disease". Retrieved 6 July 2020.
## External links[edit]
Classification
D
* ICD-10: E72.0
* ICD-9-CM: 270.0
* OMIM: 234500
* MeSH: D006250
* DiseasesDB: 5638
External resources
* MedlinePlus: 001201
* eMedicine: derm/713
* Orphanet: 2116
* v
* t
* e
Inborn error of amino acid metabolism
K→acetyl-CoA
Lysine/straight chain
* Glutaric acidemia type 1
* type 2
* Hyperlysinemia
* Pipecolic acidemia
* Saccharopinuria
Leucine
* 3-hydroxy-3-methylglutaryl-CoA lyase deficiency
* 3-Methylcrotonyl-CoA carboxylase deficiency
* 3-Methylglutaconic aciduria 1
* Isovaleric acidemia
* Maple syrup urine disease
Tryptophan
* Hypertryptophanemia
G
G→pyruvate→citrate
Glycine
* D-Glyceric acidemia
* Glutathione synthetase deficiency
* Sarcosinemia
* Glycine→Creatine: GAMT deficiency
* Glycine encephalopathy
G→glutamate→
α-ketoglutarate
Histidine
* Carnosinemia
* Histidinemia
* Urocanic aciduria
Proline
* Hyperprolinemia
* Prolidase deficiency
Glutamate/glutamine
* SSADHD
G→propionyl-CoA→
succinyl-CoA
Valine
* Hypervalinemia
* Isobutyryl-CoA dehydrogenase deficiency
* Maple syrup urine disease
Isoleucine
* 2-Methylbutyryl-CoA dehydrogenase deficiency
* Beta-ketothiolase deficiency
* Maple syrup urine disease
Methionine
* Cystathioninuria
* Homocystinuria
* Hypermethioninemia
General BC/OA
* Methylmalonic acidemia
* Methylmalonyl-CoA mutase deficiency
* Propionic acidemia
G→fumarate
Phenylalanine/tyrosine
Phenylketonuria
* 6-Pyruvoyltetrahydropterin synthase deficiency
* Tetrahydrobiopterin deficiency
Tyrosinemia
* Alkaptonuria/Ochronosis
* Tyrosinemia type I
* Tyrosinemia type II
* Tyrosinemia type III/Hawkinsinuria
Tyrosine→Melanin
* Albinism: Ocular albinism (1)
* Oculocutaneous albinism (Hermansky–Pudlak syndrome)
* Waardenburg syndrome
Tyrosine→Norepinephrine
* Dopamine beta hydroxylase deficiency
* reverse: Brunner syndrome
G→oxaloacetate
Urea cycle/Hyperammonemia
(arginine
* aspartate)
* Argininemia
* Argininosuccinic aciduria
* Carbamoyl phosphate synthetase I deficiency
* Citrullinemia
* N-Acetylglutamate synthase deficiency
* Ornithine transcarbamylase deficiency/translocase deficiency
Transport/
IE of RTT
* Solute carrier family: Cystinuria
* Hartnup disease
* Iminoglycinuria
* Lysinuric protein intolerance
* Fanconi syndrome: Oculocerebrorenal syndrome
* Cystinosis
Other
* 2-Hydroxyglutaric aciduria
* Aminoacylase 1 deficiency
* Ethylmalonic encephalopathy
* Fumarase deficiency
* Trimethylaminuria
* v
* t
* e
Genetic disorder, membrane: Solute carrier disorders
1-10
* SLC1A3
* Episodic ataxia 6
* SLC2A1
* De Vivo disease
* SLC2A5
* Fructose malabsorption
* SLC2A10
* Arterial tortuosity syndrome
* SLC3A1
* Cystinuria
* SLC4A1
* Hereditary spherocytosis 4/Hereditary elliptocytosis 4
* SLC4A11
* Congenital endothelial dystrophy type 2
* Fuchs' dystrophy 4
* SLC5A1
* Glucose-galactose malabsorption
* SLC5A2
* Renal glycosuria
* SLC5A5
* Thyroid dyshormonogenesis type 1
* SLC6A19
* Hartnup disease
* SLC7A7
* Lysinuric protein intolerance
* SLC7A9
* Cystinuria
11-20
* SLC11A1
* Crohn's disease
* SLC12A3
* Gitelman syndrome
* SLC16A1
* HHF7
* SLC16A2
* Allan–Herndon–Dudley syndrome
* SLC17A5
* Salla disease
* SLC17A8
* DFNA25
21-40
* SLC26A2
* Multiple epiphyseal dysplasia 4
* Achondrogenesis type 1B
* Recessive multiple epiphyseal dysplasia
* Atelosteogenesis, type II
* Diastrophic dysplasia
* SLC26A4
* Pendred syndrome
* SLC35C1
* CDOG 2C
* SLC39A4
* Acrodermatitis enteropathica
* SLC40A1
* African iron overload
see also solute carrier family
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Hartnup disease
|
c0018609
| 7,379 |
wikipedia
|
https://en.wikipedia.org/wiki/Hartnup_disease
| 2021-01-18T18:35:01 |
{"gard": ["6569"], "mesh": ["D006250"], "umls": ["C0018609"], "icd-9": ["270.0"], "orphanet": ["2116"], "wikidata": ["Q200985"]}
|
A rare inborn error of metabolism characterized by elevated levels of imino acids (proline, hydroxyproline) and glycine in urine due to defective reabsorption in the kidney. The condition is considered benign and not associated with any specific clinical phenotype. Mode of inheritance is autosomal recessive.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Iminoglycinuria
|
c0268654
| 7,380 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=42062
| 2021-01-23T18:03:33 |
{"gard": ["8424"], "mesh": ["C536285"], "omim": ["242600"], "umls": ["C0268654"], "icd-10": ["E72.0"]}
|
White plague is a suite of coral diseases of which three types have been identified, initially in the Florida Keys. They are infectious diseases but it has proved difficult to identify the pathogens involved. White plague type II may be caused by the gram negative bacterium Aurantimonas coralicida in the order Rhizobiales but other bacteria have also been associated with diseased corals and viruses may also be implicated.
## History[edit]
In 1977, a disease of scleractinian corals appeared on reefs off the Florida Keys in the United States and was termed white plague. It caused white lesions and was shown to be an infectious disease, being particularly prevalent in Mycetophyllia ferox. This disease caused little mortality and occurred sporadically, but was still present in the area in 1984. It is now known as white plague type 1.[1]
In 1995, a new coral disease was described as an epizootic disease in the same reefs in the Florida Keys. Many species of coral found in the area were affected and the mortality rate of these was up to 38%. The pathogen involved was found to be a previously unknown species of bacterium in the order Rhizobiales, which was placed in the newly created genus Aurantimonas and given the name Aurantimonas coralicida, and the disease was described as white plague type 2.[2] The pathogen was isolated from a diseased colony of Dichocoenia stokesi and cultured in the laboratory, subsequently being used to inoculate two healthy colonies which then developed the disease.[3] In the next few months, it had spread over 200 km (124 mi) of reef and was killing seventeen species of coral. Over the next four years, it spread further, but was most severe in different regions each year.[1]
White plague is an enigmatic disease. Further research cast into doubt the role of A. coralicida as a causative agent by finding that bacterium on healthy parts of colonies of Orbicella annularis affected by white plague disease but absent from diseased parts. In these diseased colonies, an α-proteobacterium similar to one which causes a disease in juvenile oysters has been implicated, being found on the diseased parts of the coral but not on the sound tissues. These anomalous findings may be caused by the fact that there are two or more diseases with similar symptoms, both known as white plague.[3]
In 1999, a third and still more virulent variant appeared in the northern Florida Keys. White plague type III mostly affected Colpophyllia natans and Orbicella annularis.[4]
A white-plague like disease reported from the Red Sea in 2005 has been shown to be caused by a different bacterial pathogen, Thalassomonas loyana. Further research has shown that viruses may be involved in white plague infections, the coral small circular ssDNA viruses (SCSDVs) being present in association with diseased tissue. This group of viruses is known to cause disease in plants and animals.[5]
## Description[edit]
As first described by College of Charleston professor Philip Dustan in 1977, white plague type 1 produces lesions on any part of the colony. These increase gradually in size, advancing at the rate of a few millimetres per day. The advancing edge exhibits a sharp boundary between the apparently healthy tissue and the bare skeleton. Type II, first appearing in 1995 is similar, but it usually starts at the base of the colony, and the edge advances at a faster rate, up to 2 cm (0.8 in) per day.[4] White plague type III advances at a rate in excess of two centimetres per day.[5]
## References[edit]
1. ^ a b Woodley, Cheryl M.; Downs, Craig A.; Bruckner, Andrew W.; Porter, James W.; Galloway, Sylvia B. (2016). Diseases of Coral. John Wiley & Sons. p. 64. ISBN 978-0-8138-2411-6.
2. ^ Denner, E.B.M. (2003). "Aurantimonas coralicida gen. nov., sp. nov., the causative agent of white plague type II on Caribbean scleractinian corals". International Journal of Systematic and Evolutionary Microbiology. 53 (4): 1115–1122. doi:10.1099/ijs.0.02359-0. ISSN 1466-5026. PMID 12892136.
3. ^ a b Woodley, Cheryl M.; Downs, Craig A.; Bruckner, Andrew W.; Porter, James W.; Galloway, Sylvia B. (2016). Diseases of Coral. John Wiley & Sons. pp. 324–326. ISBN 978-0-8138-2411-6.
4. ^ a b Rosenberg, Eugene; Loya, Yossi (2004). Coral Health and Disease. Springer Science & Business Media. p. 352. ISBN 978-3-540-20772-6.
5. ^ a b Soffer, Nitzan; Brandt, Marilyn E.; Correa, Adrienne M.S.; Smith, Tyler B.; Thurber, Rebecca Vega (2014). "Potential role of viruses in white plague coral disease". ISME Journal. 8 (2): 271–283. doi:10.1038/ismej.2013.137. PMC 3906806. PMID 23949663.CS1 maint: multiple names: authors list (link)
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
White plague (coral disease)
|
None
| 7,381 |
wikipedia
|
https://en.wikipedia.org/wiki/White_plague_(coral_disease)
| 2021-01-18T18:33:49 |
{"wikidata": ["Q48997936"]}
|
MODY 6
Other namesMaturity-Onset Diabetes of the Young, Type 6
MODY 6 is a form of maturity onset diabetes of the young.
MODY 6 arises from mutations of the gene for the transcription factor referred to as neurogenic differentiation 1. The gene is on chromosome 2 in a region of the p arm known as IDDM7 because it includes genes affecting susceptibility to diabetes mellitus type 1 (NeuroD1).[1] NeuroD1 promotes transcription of the insulin gene as well as some genes involved in formation of beta cells and parts of the nervous system.
This is also one of the rarer forms of MODY. Only 3 kindreds with mutations causing MODY6 have been identified so far. In both, some of the members had more typical type 2 diabetes rather than MODY, and the reasons for the difference of expression have not been worked out. Most of the family members with diabetes were diagnosed after age 40, but a few required insulin for blood sugar control.
## References[edit]
1. ^ Copeman JB, Cucca F, Hearne CM, et al. (January 1995). "Linkage disequilibrium mapping of a type 1 diabetes susceptibility gene (IDDM7) to chromosome 2q31-q33". Nat. Genet. 9 (1): 80–5. doi:10.1038/ng0195-80. PMID 7704030.
## External links[edit]
Classification
D
* OMIM: 606394
* MeSH: C565231
* v
* t
* e
Disease of the pancreas and glucose metabolism
Diabetes
* Types
* type 1
* type 2
* gestational
* MODY 1 2 3 4 5 6
* Complications
* See Template:Diabetes
Abnormal blood glucose levels
* Hyperglycaemia
* Oxyhyperglycemia
* Hypoglycaemia
* Whipple's triad
Insulin disorders
* Insulin resistance
* Hyperinsulinism
* Rabson–Mendenhall syndrome
Other pancreatic disorders
* Insulinoma
* Insulitis
* v
* t
* e
Genetic disorders relating to deficiencies of transcription factor or coregulators
(1) Basic domains
1.2
* Feingold syndrome
* Saethre–Chotzen syndrome
1.3
* Tietz syndrome
(2) Zinc finger
DNA-binding domains
2.1
* (Intracellular receptor): Thyroid hormone resistance
* Androgen insensitivity syndrome
* PAIS
* MAIS
* CAIS
* Kennedy's disease
* PHA1AD pseudohypoaldosteronism
* Estrogen insensitivity syndrome
* X-linked adrenal hypoplasia congenita
* MODY 1
* Familial partial lipodystrophy 3
* SF1 XY gonadal dysgenesis
2.2
* Barakat syndrome
* Tricho–rhino–phalangeal syndrome
2.3
* Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome
* Denys–Drash syndrome
* Duane-radial ray syndrome
* MODY 7
* MRX 89
* Townes–Brocks syndrome
* Acrocallosal syndrome
* Myotonic dystrophy 2
2.5
* Autoimmune polyendocrine syndrome type 1
(3) Helix-turn-helix domains
3.1
* ARX
* Ohtahara syndrome
* Lissencephaly X2
* MNX1
* Currarino syndrome
* HOXD13
* SPD1 synpolydactyly
* PDX1
* MODY 4
* LMX1B
* Nail–patella syndrome
* MSX1
* Tooth and nail syndrome
* OFC5
* PITX2
* Axenfeld syndrome 1
* POU4F3
* DFNA15
* POU3F4
* DFNX2
* ZEB1
* Posterior polymorphous corneal dystrophy
* Fuchs' dystrophy 3
* ZEB2
* Mowat–Wilson syndrome
3.2
* PAX2
* Papillorenal syndrome
* PAX3
* Waardenburg syndrome 1&3
* PAX4
* MODY 9
* PAX6
* Gillespie syndrome
* Coloboma of optic nerve
* PAX8
* Congenital hypothyroidism 2
* PAX9
* STHAG3
3.3
* FOXC1
* Axenfeld syndrome 3
* Iridogoniodysgenesis, dominant type
* FOXC2
* Lymphedema–distichiasis syndrome
* FOXE1
* Bamforth–Lazarus syndrome
* FOXE3
* Anterior segment mesenchymal dysgenesis
* FOXF1
* ACD/MPV
* FOXI1
* Enlarged vestibular aqueduct
* FOXL2
* Premature ovarian failure 3
* FOXP3
* IPEX
3.5
* IRF6
* Van der Woude syndrome
* Popliteal pterygium syndrome
(4) β-Scaffold factors
with minor groove contacts
4.2
* Hyperimmunoglobulin E syndrome
4.3
* Holt–Oram syndrome
* Li–Fraumeni syndrome
* Ulnar–mammary syndrome
4.7
* Campomelic dysplasia
* MODY 3
* MODY 5
* SF1
* SRY XY gonadal dysgenesis
* Premature ovarian failure 7
* SOX10
* Waardenburg syndrome 4c
* Yemenite deaf-blind hypopigmentation syndrome
4.11
* Cleidocranial dysostosis
(0) Other transcription factors
0.6
* Kabuki syndrome
Ungrouped
* TCF4
* Pitt–Hopkins syndrome
* ZFP57
* TNDM1
* TP63
* Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8
Transcription coregulators
Coactivator:
* CREBBP
* Rubinstein–Taybi syndrome
Corepressor:
* HR (Atrichia with papular lesions)
This article about an endocrine, nutritional, or metabolic disease is a stub. You can help Wikipedia by expanding it.
* v
* t
* e
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
MODY 6
|
c1853371
| 7,382 |
wikipedia
|
https://en.wikipedia.org/wiki/MODY_6
| 2021-01-18T19:10:10 |
{"mesh": ["C565231"], "wikidata": ["Q6717008"]}
|
A number sign (#) is used with this entry because of evidence that autosomal recessive progressive external ophthalmoplegia with mitochondrial DNA deletions-5 (PEOB5) is caused by compound heterozygous mutation in the TOP3A gene (601243) on chromosome 17p11. One such patient has been reported.
For a discussion of genetic heterogeneity of autosomal recessive PEO, see PEOB1 (258450).
Clinical Features
Nicholls et al. (2018) reported a 67-year-old woman who presented with slowly progressive ptosis, intermittent double vision, mild dysphagia and nasal regurgitation, and sensorineural hearing loss. Additional features included rapid cycling mood disorder, cardiac arrhythmias necessitating a pacemaker, exercise intolerance, and cerebellar ataxia. Physical examination was consistent with progressive external ophthalmoplegia, and other findings included dysarthria, proximal limb and neck muscle weakness, upper limb dysmetria, and broad-based gait. Nerve conduction studies showed a mild sensory neuropathy, and brain imaging showed cerebellar atrophy and symmetric changes in the thalami and midbrain. Echocardiogram showed impaired left ventricular function, ectopic beats, and tachycardia. Patient skeletal muscle biopsy showed numerous COX-deficient ragged-red fibers, increased mtDNA deletions (over 80%), and extensive variable mtDNA rearrangements.
Molecular Genetics
In a 67-year-old woman with PEOB5, Nicholls et al. (2018) identified compound heterozygous mutations in the TOP3A gene (M100V, 601243.0004 and R135X, 601243.0005). The mutations, which were found by whole-exome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family, although DNA from the deceased unaffected father was not available. The R135X variant was predicted to result in a loss of function. In vitro functional expression studies showed that the M100V variant had impaired catalytic activity, and patient cells showed increased levels of catenated mtDNA compared to controls. The findings illustrated the important role of TOP3A in mtDNA replication and separation.
INHERITANCE \- Autosomal recessive HEAD & NECK Ears \- Sensorineural hearing loss Eyes \- Progressive external ophthalmoplegia \- Ptosis \- Double vision Nose \- Nasal regurgitation Neck \- Neck muscle weakness CARDIOVASCULAR Heart \- Cardiac arrhythmia \- Impaired left ventricular function ABDOMEN Gastrointestinal \- Dysphagia MUSCLE, SOFT TISSUES \- Exercise intolerance \- Proximal muscle weakness \- COX-deficient ragged-red fibers seen on skeletal muscle biopsy \- Increased mtDNA deletions \- mtDNA rearrangements NEUROLOGIC Central Nervous System \- Cerebellar ataxia \- Dysmetria \- Dysarthria \- Broad-based gait \- Cerebellar atrophy \- Symmetric changes in the thalami and midbrain Peripheral Nervous System \- Sensory neuropathy Behavioral Psychiatric Manifestations \- Cycling mood disorder MISCELLANEOUS \- Adult onset \- One patient has been reported (last curated September 2018) MOLECULAR BASIS \- Caused by mutation in the topoisomerase, DNA, III, alpha gene (TOP3A, 601243.0004 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL RECESSIVE 5
|
None
| 7,383 |
omim
|
https://www.omim.org/entry/618098
| 2019-09-22T15:43:37 |
{"omim": ["618098"], "synonyms": ["Alternative titles", "PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA, AUTOSOMAL RECESSIVE 5"]}
|
A number sign (#) is used with this entry because of evidence that mitochondrial complex I deficiency nuclear type 21 (MC1DN21) is caused by homozygous or compound heterozygous mutation in the NUBPL gene (613621) on chromosome 14q12.
For a discussion of genetic heterogeneity of mitochondrial complex I deficiency, see 252010.
Clinical Features
Calvo et al. (2010) reported a patient with mitochondrial complex I deficiency who presented at 2 years of age with developmental delay, particularly of motor skills. He never achieved independent walking. He developed myopathy, nystagmus, ataxia, upper motor neuron signs, and absence seizures. Brain MRI showed leukodystrophy with involvement of the cerebellar cortex and deep white matter. At age 8, he had spasticity, ataxia, and speech problems. Patient fibroblasts had only 19% residual complex I activity on spectrophometric enzyme assay and 40% residual activity using dipstick assay. Transduction of patient fibroblasts with wildtype NUBPL restored complex I activity.
Kevelam et al. (2013) reported 6 patients, including 2 sibs, with complex I deficiency. All patients had a characteristic leukoencephalopathic pattern on brain MRI. Initial studies showed confluent or multifocal cerebral white matter lesions, predominantly affecting the deep white matter while sparing the U-fibers and internal and external capsules. There were also signal abnormalities and swelling of the corpus callosum. Signal abnormalities were present in the cerebellar cortex, but not in the deep white matter. Later imaging of most patients showed improvement of the cerebral white matter and corpus callosum abnormalities, but worsening of the cerebellar abnormalities and additional brainstem abnormalities. One patient had severe atrophy of the corpus callosum. All patients developed motor problems due to ataxia in the first years of life, but other features were somewhat variable: some patients showed continuous regression and others showed episodic regression. Five patients had spasticity and only 2 achieved unsupported walking.Cognitive capabilities varied between normal and significantly deficient. Complex I deficiency ranged between 27% and 83% of normal, and there was no correlation between residual complex I activity and clinical severity.
Molecular Genetics
In a patient with mitochondrial complex I deficiency nuclear type 21, Calvo et al. (2010) identified compound heterozygosity for 2 mutations in the NUBPL gene (613621.0001 and 613621.0002).
In 6 patients from 5 unrelated families with complex I deficiency and a characteristic leukoencephalopathic pattern on brain MRI, Kevelam et al. (2013) identified biallelic mutations in the NUBPL gene (613621.0001; 613621.0003-613621.0006). All patients carried at least 1 copy of a complex allele (G56R/c.815-27T-C; 613621.0001).
INHERITANCE \- Autosomal recessive GROWTH Other \- Poor growth HEAD & NECK Eyes \- Nystagmus \- Strabismus MUSCLE, SOFT TISSUES \- Hypotonia, axial \- Hypertonia, limb \- Myopathy NEUROLOGIC Central Nervous System \- Global developmental delay \- Loss of developmental skills \- Cognitive development may be significantly impaired or normal \- Difficulty walking \- Ataxia \- Upper motor neuron signs \- Absence seizures (in some patients) \- Poor speech \- Dysarthria \- Spasticity \- Hyperreflexia \- Extensor plantar responses \- Leukodystrophy \- Leukoencephalopathy \- Corpus callosum abnormalities \- Brainstem abnormalities \- Cerebellar abnormalities LABORATORY ABNORMALITIES \- Mitochondrial complex I deficiency in various tissues MISCELLANEOUS \- Variable severity \- Variable progression \- Some patients may show neurologic regression MOLECULAR BASIS \- Caused by mutation in the nucleotide-binding protein-like protein gene (NUBPL, 613621.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 21
|
c2936907
| 7,384 |
omim
|
https://www.omim.org/entry/618242
| 2019-09-22T15:42:52 |
{"mesh": ["C537475"], "omim": ["618242"], "orphanet": ["2609"]}
|
Eye injuries during general anaesthesia are reasonably common if care is not taken to prevent them.
## Contents
* 1 Incidence of eye injuries
* 2 Effect of general anaesthesia on eyes
* 3 Mechanism of Injury
* 4 Methods available for eye injury prevention
* 5 Discussion of methods
* 6 Adverse outcomes associated with intra-operative eye injuries
* 7 References
## Incidence of eye injuries[edit]
The incidence of eye injuries during general anaesthesia has been studied, and different methods of eye protection have been compared.
When eyes are untaped during general anaesthesia, the incidence of ocular injury has been reported to be as high as 44%.[1][2] If tape is used to hold the eyes closed, ocular injury occurs during 0.1-0.5% of general anaesthetics, and is usually corneal in nature.[3][4]
Intraoperative eye injuries account for 2% of medico-legal claims against anaesthetists in Australia and United Kingdom,[3][1] and 3% in the USA.[5]
## Effect of general anaesthesia on eyes[edit]
General anaesthesia reduces the tonic contraction of the orbicularis oculi muscle, causing lagophthalmos i.e. the eyelids do not close fully in 59% of patients.[3]
In addition, general anaesthesia reduces tear production and tear-film stability, resulting in corneal epithelial drying and reduced lysosomal protection. The protection afforded by Bell's phenomenon (in which the eyeball turns upwards during sleep, protecting the cornea) is also lost during general anaesthesia.[6]
## Mechanism of Injury[edit]
Corneal abrasions are the most common injury; they are caused by direct trauma, exposure keratopathy/keratitis[1][7][8] or chemical injury.[7][9]
An open eye increases the vulnerability of the cornea to direct trauma from objects such as face masks, laryngoscopes, identification badges, stethoscopes, surgical instruments, anaesthetic circuits, and drapes.[6]
Exposure keratopathy/keratitis refers to the drying of the cornea with subsequent epithelial breakdown.[10] When the cornea dries out it may stick to the eyelid and cause an abrasion when the eye reopens.[11]
Exposure keratitis
Chemical injury can occur if cleaning solutions such as povidone-iodine (Betadine), chlorhexidine or alcohol are inadvertently spilt into the eye, for example when the face, neck or shoulder is being prepped for surgery.[4][1]
Therefore, the anaesthetist ensures that the eyes are fully closed and remain closed throughout the procedure. Seemingly trivial contact can result in corneal abrasions and the risk of this occurring is markedly increased if exposure keratopathy is already present.[1] Corneal abrasions can be excruciatingly painful in the postoperative period, may hamper postoperative rehabilitation and may require ongoing ophthalmological review and after care. In extreme cases there may be partial or complete visual loss.
Iatrogenic injury of the eyelids is also common. Bruising (frequently) and tearing (rarely) of the eyelid can occur when the adhesive dressing used to hold the eye closed is removed. Removal of eyelashes can also occur.
## Methods available for eye injury prevention[edit]
Methods to prevent intraoperative corneal injuries include
* simple manual closure of the eyelids
* holding the eyelids shut with tape or a general purpose adhesive dressing
* use of a specially designed eyelid occlusion dressing
* use of eye ointment (although this is controversial, see below)
* bio-occlusive dressings
* suture tarsorrhaphy
However, none of the protective strategies are completely effective; vigilance is always required i.e. the eyes need to be inspected regularly throughout surgery to check they are closed.[3]
## Discussion of methods[edit]
The most commonly employed method is to use tape or a general purpose adhesive dressing. Unfortunately the adhesive used on the tape or dressing will generally be inappropriate for this use. The adhesive strength may change when reaching body temperature, or over time.[12]
As the operation progresses this can cause the adhesive to stop working and become gooey, allowing the eyelids to move apart, and leaving behind a sticky residue. This leaves the cornea exposed to epithelial drying and/or abrasions, sometimes caused by the tape that was originally applied to protect the cornea. Alternatively, the adhesive strength may increase, which upon removal can result in eyelid bruising, tears, or eyelash removal.
Tape being removed off eye
Rolls of tapes are often “laying around” the operating theatre or kept in health care workers' pockets.
Tape awaiting placement
Therefore, they can be a source of hospital-acquired infections (HAI's) such as Methicillin-resistant Staphylococcus aureus (MRSA) & Vancomycin-resistant Enterococcus (VRE), with a 2010 study showing that 50% of partially used tape rolls tested positive for MRSA, VRE or both.[13]
Most tapes and dressings are non-transparent and so it is not possible to see if the patient’s eyes are opened or closed throughout the case. It is not uncommon for the eyelids to move open as the case progresses, even with adhesive tapes stuck onto them. In a practical sense, these medical tapes/dressings may be difficult to remove from a patient because their ends can become stuck flush with the skin. The possibility of tape removal causing trauma is also significantly increased in older people, people with sensitive skin, dermatitis, dehydration or side effects of medications.[14]
As noted above, there have been several studies looking at the efficacy and safety of eye ointments/lubricants as adjuncts with tape or as a stand-alone management for intra-operative eye closure. Unfortunately many in common use have problems. Petroleum gel is flammable and is best avoided when electrocautery and open oxygen are to be used around the face. Preservative-free eye ointment is preferred, as preservative can cause corneal epithelial sloughing and conjunctival hyperemia.[9] They have been implicated in blurred vision in up to 75% of patients and they do not protect from direct trauma.[6][15]
Specially made eyelid occlusion dressings are available commercially, such as EyeGard (manufactured in the USA by KMI Surgical and marketed by Sharn Anesthesia), EyePro (Innovgas Pty Ltd, Australia) and Anesthesia-Aid (Sperian Protection). These dressings overcome most of the problems associated with tape or general purpose dressings.
## Adverse outcomes associated with intra-operative eye injuries[edit]
Some of the adverse outcomes associated with intra-operative injuries include:
* Increased length of stay. This is due to ophthalmology consults required, associated infections and treatment.[15]
* Increased costs. This is due to increased length of stay, cost of treating the complications.[16]
* Pain and discomfort for the patient. Corneal abrasions are extremely painful for the patient and the treatment consists of drops and ointments applied in the eye which may cause further discomfort for the patient.[15][16]
## References[edit]
1. ^ a b c d e C Marcucci, NA Cohen, DG Metro & JR Kirsch 2008, Avoiding Common Anesthesia Errors, Lippincott Williams & Wilkins, Philadelphia PA USA.
2. ^ Kocaturk, O, Kocaturk, T, Kaan, N & Dayanir V 2012 'The Comparison of Four Different Methods of Perioperative Eye Protection under General Anesthesia in Prone Position', Journal of Clinical and Analytical Medicine, vol. 3, no. 2, pp. 163-5 "Read Article"
3. ^ a b c d S Contractor & JG Hardman 2006, 'Injury During Anaesthesia', Continuing Education in Anaesthesia, Critical Care & Pain, vol. 6, no. 2, pp. 67-70, "Read Article"
4. ^ a b VK Grover, KV Kumar, S Sharma & SP Grewal 1998, 'Comparison of Methods of Eye Protection under General Anaesthesia', Canadian Journal of Anesthesia, vol. 45, no. 6, pp. 575-7, "Read Article"
5. ^ J Anson, 'Perioperative Corneal Abrasions: Etiology, Prevention, and Management', Pennsylvania Society of Anesthesiologists, "Read Article".
6. ^ a b c PN Nair & E White 2014, 'Care of the Eye During Anaesthesia and Intensive Care', Anaesthesia and Intensive Care Medicine, vol. 15, no. 1, pp. 40-43, "Read Article".
7. ^ a b E White 2004, 'Care of the eye during anaesthesia', Anaesthesia and Intensive Care Medicine, vol. 5, pp. 302-3 "Read Article".
8. ^ K Zheng, CG Guta, V Kulkarni & J Brock-Utne 2009, 'Prevention of Corneal Abrasions in Patients with Autoimmune Dry Eyes', Anaesthesia and Analgesia, vol. 108, no. 1, pp. 385-6, "Read Article"
9. ^ a b A Grixti, M Sadri & MT Watts 2013, 'Corneal Protection during General Anesthesia for Nonocular Surgery', The Ocular Surface, vol. 11, no. 2, pp. 109-18, "Read Article"
10. ^ NJ Friedman & PK Kaiser 2007, Essentials of Ophthalmology, Elsevier Health Sciences, Philadelphia PA USA.
11. ^ N Tarmey & LA White 2009, 'Section 5: Damage to the eye during General Anaesthesia', Risk Associated with your Anaesthetic, Royal College of Anaesthetists website, "Read Article".
12. ^ AN Gent 1996, 'Adhesion and strength of viscoelastic solids. Is there a relationship between adhesion and bulk properties?', Langmuir, vol. 12, no. 19, pp. 4492-96, "Read Article".
13. ^ Clinical and Laboratory Standards Institute 2010, 'Performance Standards for Antimicrobial Susceptibility testing: Twentieth Informational Supplement', CLSI Document M100-S20"Read Article".
14. ^ C Konya, H Sanada, J Sugama, M Okuwa, Y Kamatani, G Nakagami & K Sakaki 2010, 'Skin Injuries Caused by Medical Adhesive Tape in Older People and Associated Factors', Journal of Clinical Nursing, vol. 19, no. 9-10, pp. 1236-1242 "Read Article".
15. ^ a b c M Weed & N Syed 2012, 'Perioperative Corneal Abrasions: Systems-based review and analysis', EyeRounds.org, "Read Article".
16. ^ a b S Prakash 2013, 'Perioperative Eye Protection under General Anaesthesia', Journal of Anaesthesiology Clinical Pharmacology, vol. 29, no. 1, pp. 138-139 "Read Article".
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Eye injuries during general anaesthesia
|
None
| 7,385 |
wikipedia
|
https://en.wikipedia.org/wiki/Eye_injuries_during_general_anaesthesia
| 2021-01-18T18:54:48 |
{"wikidata": ["Q17155694"]}
|
Drug-induced localized lipodystrophy is a rare, acquired, localized lipodystrophy characterized by the appearance of asymptomatic, well-demarcated, variably sized, depressed, lipoatrophic lesions secondary to subcutaneous, intradermic or intramuscular drug injection, including corticosteroids, insulin, human growth hormone and antibiotics. Skin coloration may vary from white or hypopigmented to reddish, pinkish or violaceous. Epidermal atrophy may be also present.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Drug-induced localized lipodystrophy
|
c1274983
| 7,386 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=90157
| 2021-01-23T17:53:59 |
{"icd-10": ["E88.1"], "synonyms": ["Lipoatrophy caused by injected drug"]}
|
## Summary
### Clinical description.
Action myoclonus – renal failure (AMRF) syndrome typically comprises a continuum of two major (and ultimately fatal) manifestations: progressive myoclonic epilepsy (PME) and renal failure; however, in some instances, the kidneys are not involved. Neurologic manifestations can appear before, simultaneously, or after the renal manifestations. Disease manifestations are usually evident in the late teens or early twenties. In the rare instances in which renal manifestations precede neurologic findings, onset is usually in late childhood / early adolescence but can range to the fifth or sixth decade. Neurologic manifestations begin with tremor at rest (which is exacerbated by fine motor activities) and progress to involuntary, action-activated myoclonic jerks that involve bulbar, proximal, and distal limb muscles; involuntary spontaneous myoclonic jerks; and generalized clonic-tonic-clonic seizures. Sensorimotor peripheral neuropathy and sensorineural hearing loss can also be observed. Renal manifestations include proteinuria that can progress to nephrotic syndrome and end-stage renal disease.
### Diagnosis/testing.
The diagnosis of AMRF syndrome is suspected in a previously healthy teenager or young adult with the characteristic neurologic and/or renal manifestations. The diagnosis is confirmed in individuals with biallelic (homozygous or compound heterozygous) loss-of-function pathogenic variants in SCARB2.
### Management.
Treatment of manifestations: Symptomatic pharmacologic and psychosocial support is the mainstay of care for the neurologic manifestations. Response to treatment is variable and may worsen over time, necessitating rehabilitative management. Renal insufficiency requires dialysis but response to treatment is poor, and renal transplantation is often necessary.
Prevention of secondary complications: Standard measures for prevention of aspiration pneumonia and sudden unexpected death in epilepsy should be followed.
Surveillance: Lifelong follow up should include regular monitoring of antiepileptic drug treatment and renal function (including urinary protein excretion, creatinine clearance, and estimated glomerular filtration rate) and periodic assessment of hearing and peripheral nerves.
Agents/circumstances to avoid: Diphenylhydantoin, carbamazepine, oxcarbazepine, and possibly lamotrigine increase myoclonus and should be avoided in any individual with PME.
Pregnancy management: Because some antiepileptic drugs can lead to an increased risk of malformations, growth retardation, or neurodevelopmental disabilities in exposed fetuses, standard measures for prevention of fetopathy should be followed.
### Genetic counseling.
AMRF syndrome is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal and preimplantation genetic testing are possible if the SCARB2 pathogenic variants in the family have been identified.
## Diagnosis
### Suggestive Findings
Action myoclonus – renal failure (AMRF) syndrome should be suspected in a previously healthy teenager or young adult with the following neurologic and renal manifestations [Andermann et al 1986, Badhwar et al 2004, Vadlamudi et al 2006, Andermann 2011]:
Neurologic manifestations
* A fine tremor of the fingers and hands, present at rest, exacerbated by fine motor activities such as writing and relieved by alcohol or propranolol, is commonly the first finding. The tremor can later involve the head, trunk, lower extremities, and sometimes tongue and voice. In the later stages of the disease, it becomes masked by striking myoclonic jerks.
* Involuntary, action-activated myoclonic jerks, also induced by attempted and executed speech, involve bulbar as well as proximal and distal limb muscles. The myoclonus is reflex-sensitive to touch on the distal extremities.
* Involuntary spontaneous myoclonic jerks of the face (particularly perioral) as well as synchronous and asynchronous jerks of the trunk and limbs also occur at rest.
* Generalized clonic-tonic-clonic seizures, diurnal and/or nocturnal, start with a generalized clonic phase with preserved consciousness and proceed to unconsciousness with tonic-clonic features and urinary incontinence.
* Other findings can include sensorimotor peripheral neuropathy (most often predominantly demyelinating or more rarely axonal) and sensorineural hearing loss (SNHL).
Renal manifestations
* Proteinuria, the first manifestation of renal disease, is initially mild and asymptomatic.
* Renal disease can progress to nephrotic syndrome and end-stage renal disease.
* In some families, renal manifestations (eventually requiring renal transplantation) appear first in late childhood or early teens and neurologic manifestations in the late twenties or early thirties [Badhwar et al 2004].
* Histologic changes include interstitial fibrosis, atrophy, focal sclerosing glomerulonephritis sometimes with features of collapsing glomerulopathy (a severe variant of glomerulosclerosis), or membranous nephropathy. No storage was observed [Andermann et al 1986, Badhwar et al 2004, Berkovic et al 2008].
* Note: Immunostaining can show IgM and complement present in the glomerular loops and in the mesangium [Andermann et al 1986]. In one patient, a C1q nephropathy has been shown by immunohistochemistry [Balreira et al 2008, Chaves et al 2011], indicating an immune complex-mediated glomerular disease. In this patient, extensive tubular abnormalities were also present, as well as granular material in cortical tubules. No Gaucher cells were observed.
A classification that takes into account the age at disease onset and the clinical manifestations has been proposed (Table 2).
### Establishing the Diagnosis
The diagnosis of action myoclonus – renal failure (AMRF) syndrome is confirmed in individuals with biallelic (homozygous or compound heterozygous) loss-of-function pathogenic variants in SCARB2 [Balreira et al 2008, Berkovic et al 2008] (Table 1).
Note: Molecular diagnosis performed early in the disease course may eliminate the need for numerous invasive neurologic and renal investigations.
Molecular genetic testing approaches can include single-gene testing, use of a multigene panel, and more comprehensive genomic testing.
Single-gene testing
* Persons of French-Canadian ancestry. It is appropriate to start with targeted analysis of the two most common pathogenic variants in that population: c.862C>T [Berkovic et al 2008] and c.1187+3insT [Dibbens et al 2011]. If no or only one pathogenic variant is found, it is appropriate to perform sequence analysis of SCARB2.
* Persons not of French-Canadian ancestry. It is appropriate to begin with sequence analysis of SCARB2. If only one pathogenic variant is identified, it is reasonable to perform gene-targeted deletion/duplication analysis next. However, to date, no SCARB2 deletion/duplication has been reported to the authors' knowledge.
A multigene panel for progressive myoclonic epilepsy (PME) or epilepsy that includes SCARB2 and other genes of interest (see Differential Diagnosis) may also be used. Note: (1) The genes included in the panel and the diagnostic sensitivity of the testing used for each gene vary by laboratory and are likely to change over time. (2) Some multigene panels may include genes not associated with the condition discussed in this GeneReview; thus, clinicians need to determine which multigene panel is most likely to identify the genetic cause of the condition at the most reasonable cost while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype. (3) In some laboratories, panel options may include a custom laboratory-designed panel and/or custom phenotype-focused exome analysis that includes genes specified by the clinician. (4) Methods used in a panel may include sequence analysis, deletion/duplication analysis, and/or other non-sequencing-based tests.
For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
More comprehensive genomic testing (when available) including exome sequencing, mitochondrial sequencing, and genome sequencing may be considered if serial single-gene testing (and/or use of a multigene panel that includes SCARB2) fails to confirm a diagnosis in an individual with features of action myoclonus – renal failure syndrome. Such testing may provide or suggest a diagnosis not previously considered (e.g., mutation of a different gene that results in a similar clinical presentation.
For an introduction to comprehensive genomic testing click here. More detailed information for clinicians ordering genomic testing can be found here.
### Table 1.
Molecular Genetic Testing Used in Action Myoclonus – Renal Failure Syndrome
View in own window
Gene 1MethodProportion of Probands with Pathogenic Variants 2 Detectable by Method
SCARB2Sequence analysis 3Estimated from Table 4: 97.5% 4
Targeted analysis of pathogenic variantsSee footnote 5
Gene-targeted deletion/duplication analysis 6None reported
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants detected in this gene.
3\.
Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
4\.
About 20 pathogenic variants have been reported to date (see Tables 3 and 4). About 2.5% of affected individuals are compound heterozygotes with an identified intragenic pathogenic variant in one allele and an unidentified variant in the other.
5\.
Testing for the pathogenic variants c.862C>T (see also Table 4) (exon 7) and c.1187+3insT (see also Table 4) (intron 9) in persons of French-Canadian origin. In this population, the vast majority of probands are homozygous for c.862C>T, whereas a small proportion are compound heterozygotes for both pathogenic variants [Dibbens et al 2011].
6\.
Gene-targeted deletion/duplication analysis detects intragenic deletions and duplications. Methods used may include quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and a gene-targeted microarray designed to detect single-exon deletions or duplications.
## Clinical Characteristics
### Clinical Description
Action myoclonus – renal failure (AMRF) syndrome typically comprises a continuum of two major (and ultimately fatal) manifestations: progressive myoclonic epilepsy (PME) and renal failure (Table 2); however, in some instances, renal failure is not observed. Thus, progressive myoclonus epilepsy without renal failure caused by biallelic SCARB2 pathogenic variants is considered to be one end of the spectrum of AMRF [Badhwar et al 2004, Dibbens et al 2009, Rubboli et al 2011, Guerrero-López et al 2012, Zeigler et al 2014].
The age of onset varies, even within the same family.
* Neurologic manifestations can appear before (in 1/3 of the cases), simultaneously, or after the renal manifestations. In juvenile AMRF onset is usually in the late teens or early twenties [Andermann et al 1986, Badhwar et al 2004].
* In some persons renal manifestations occur early (late childhood or early teens) and neurologic involvement much later (late 20s or early 30s) [Badhwar et al 2004, Hopfner et al 2011].
* In three persons of Japanese heritage who did not develop renal failure, neurologic manifestations appeared in the fifth or sixth decade [Higashiyama et al 2013, Fu et al 2014].
The neurologic and renal manifestations progress independently. Of note, the neurologic manifestations are not the result of a metabolic encephalopathy due to renal failure and are not improved by dialysis or by renal transplantation [Andermann et al 1986, Badhwar et al 2004].
Even in the same family, the number and order of appearance of the clinical manifestations can vary. Neurologic manifestations may occur first or in isolation in some family members and renal manifestations may be first or isolated in other family members [Badhwar et al 2004]. In some families, all affected individuals have neurologic manifestations and none develop renal failure [Dibbens et al 2009, Rubboli et al 2011, Guerrero-López et al 2012, Fu et al 2014, Perandones et al 2014, Zeigler et al 2014]; however, some affected family members have proteinuria [Dibbens et al 2009, Guerrero-López et al 2012] or reduced creatinine clearance [Zeigler et al 2014].
The disease progresses relentlessly with neurologic deterioration (especially increasing severity of myoclonus) and renal failure leading to death within seven to 15 years after onset.
### Table 2.
Clinical Manifestations of AMRF
View in own window
Disease OnsetMajor ManifestationsCNS InvolvementRenal DiseaseOther Possible Manifestations
JuvenilePME and RF
* Tremor
* Progressive action myoclonus
* Myoclonus at rest
* Ataxia, dysarthria
* Severe epileptic photosensitivity
* GTCS (rare at onset; relatively infrequent even in later stages)
* Proteinuria (progressing from mild to severe)
* Segmental GP and/or TP
* Renal failure
* PNP
* SNHL
* DCM
PME
* Tremor
* Progressive action myoclonus
* Myoclonus at rest
* Ataxia, dysarthria
* Severe epileptic photosensitivity
* GTCS (infrequent at onset)
* Mild proteinuria
* Mild decrease of creatinine clearance
* PNP
* Mild generalized muscle atrophy w/out fasciculations
RFNeurologic manifestations as listed above may develop late in disease course.
* May begin in early childhood or early teens
* Proteinuria, progressive
* Segmental GP
* TP
* Renal failure
LatePME
* Tremor
* Ataxia, dysarthria
* Progressive action myoclonus
* GTCS may occur infrequently
* Cognitive decline
None reported
DCM = dilated cardiomyopathy; GP = glomerulopathy; GTCS = generalized tonic-clonic seizures; PME = progressive myoclonus epilepsy; PNP = peripheral neuropathy; RF = renal failure; SNHL = sensorineural hearing loss; TP = tubulopathy
#### Neurologic Disease
Fine tremor. The disease begins with bilateral fine tremor of the fingers that is noted at rest and increased by delicate movement such as writing, by intention of movement, and by maintaining an attitude in horizontal extension [Andermann et al 1986, Badhwar et al 2004, Vadlamudi et al 2006]. The tremor can be relieved by alcohol [Andermann et al 1986, Andermann 2011, Guerrero-López et al 2012]. It becomes progressively worse until it is masked by myoclonic jerks [Badhwar et al 2004, Vadlamudi et al 2006].
Action myoclonus. The fine tremor is followed by jerking movements first of the upper and then of the lower extremities. Referred to as action myoclonus, these jerking movements are typically triggered by movements or intended movements. They are asynchronous and of variable severity.
With time, myoclonic jerks involve the proximal limbs; their amplitude and number increases by movements of the limbs, typically by walking down stairs. Action myoclonus can also involve the trunk. Attempts at speaking and executed speech can induce myoclonus of the bulbar musculature, contributing to the dysarthria. There is no palatal myoclonus.
Action myoclonus, which is also reflex-sensitive to touch over the distal extremities, can be exacerbated by anxiety, excitement, stress, and fatigue [Badhwar et al 2004, Zeigler et al 2014] and by auditory stimuli [Perandones et al 2012]. Some patients exhibit occasional myoclonus in response to startle [Badhwar et al 2004]. Of note, myoclonic jerks were significantly less frequent during pregnancy in one patient [Amrom et al, In press].
Action myoclonus represents the most disabling manifestation: it prevents affected individuals from being able to feed themselves and, thus, they become malnourished unless they receive assistance with feeding or are fed by artificial means. In the final stages, they may become bedridden or wheelchair bound. Swallowing difficulties can lead to aspiration pneumonia and death [Andermann et al 1986, Badhwar et al 2004, Vadlamudi et al 2006].
Myoclonus at rest. Subtle myoclonic movements of the eyelids, jaws, and perioral musculature appear at rest and while speaking. Ocular dysmetria can occur later in the disease course.
Clonic-tonic-clonic seizures, which can be diurnal or nocturnal, begin with generalized clonic jerking with preserved consciousness and proceed to unconsciousness with tonic-clonic features. They occur infrequently, starting with one per annum initially [Badhwar et al 2004]. TV viewing or other light stimulation may trigger generalized myoclonic seizures or tonic-clonic seizures [Rubboli et al 2011]. Photosensitivity can become so severe that affected individuals choose to live in almost complete darkness [Rubboli et al 2011].
Ataxia and dysarthria, common findings, can be distinguished from myoclonic jerks by the presence of the cerebellar abnormalities of pendular reflexes, abnormal rebound, and hypermetric ocular saccades.
Progressive myoclonus ataxia. Some patients develop significant progressive ataxia before or after the appearance of myoclonus and, thus, have been reported to have "progressive myoclonus ataxia."
A woman age 29 years had a history of clumsiness in the lower limbs, mild gait instability, and difficulties in riding a bicycle beginning at age 21 years, two years before the onset of progressive myoclonus at age 23 years. Renal failure was evident at age 25 years, and bilateral severe SNHL was diagnosed at age 27 years [Perandones et al 2012, Perandones et al 2014].
A woman age 22 years developed postural hand tremor exacerbated by fine voluntary movements and stress. The tremor slowly worsened with multifocal spontaneous and stimulus-sensitive myoclonic jerks. No other seizures were reported, and the EEG did not show any epileptic activity (of note, the patient was taking several antiepileptic medications). Ataxia was first reported when she was wheelchair bound at age 27 years. The co-occurrence of tremor, myoclonus, and ataxia in the same patient – without generalized tonic-clonic seizures – increases the complexity of the clinical picture of this disorder [Guerrero-López et al 2012].
Peripheral neuropathy. In some families, a sensorimotor peripheral neuropathy (most often predominantly demyelinating or more rarely axonal) may be present.
Some affected individuals may be diagnosed with a predominantly demyelinating peripheral neuropathy before the onset of renal failure [Badhwar et al 2004, Costello et al 2009, Dibbens et al 2011, Hopfner et al 2011]. In the German Family I reported by Badhwar et al [2004], one family member with AMRF who was asymptomatic for polyneuropathy was initially found to have a predominantly axonal neuropathy by nerve conduction studies; several years later, he and his two affected sibs were reported to have predominantly demyelinating polyneuropathy [Hopfner et al 2011].
Mild generalized muscle atrophy was observed in one individual who exhibited mild generalized reduced tone and no fasciculations [Zeigler et al 2014].
#### Renal Disease
Mild proteinuria may progress to nephrotic syndrome and ultimately to renal failure (Table 2).
Dialysis and renal transplantation can prolong survival, but do not improve the neurologic features.
#### Mental Status
Cognitive function. Unlike individuals with most other types of progressive myoclonus epilepsy, the majority of individuals with AMRF syndrome remain mentally alert. However, dementia has been documented in two unrelated individuals of Japanese ancestry, one with the juvenile-onset form, and the other with the late-onset form, who have different SCARB2 pathogenic variants [Fu et al 2014].
Psychological complications. Individuals with AMRF may exhibit somatic concerns or depressed mood, or may in exceptional cases commit suicide [Amrom et al, In press].
#### Other Findings
Cardiac disease. In a German family, echocardiography revealed dilated cardiomyopathy in two of three affected sibs at ages 14 and 21 years [Hopfner et al 2011]. In addition, these sibs had sensorimotor peripheral neuropathy.
Hearing loss / deafness. Frank or subclinical sensorineural hearing loss (SNHL) can be part of the spectrum of AMRF syndrome. Three individuals with AMRF had adult-onset SNHL, which was mild in one individual from one family [Rubboli et al 2011] and severe and asymmetric in an individual from a second family [Perandones et al 2012], in which a sister had preclinical hearing loss [Perandones et al 2014].
Thus in the same family, the SNHL can be severe or subclinical or absent [Badhwar et al 2004, Perandones et al 2012, Perandones et al 2014].
Common causes of death in AMRF. Sudden death may occur during or after a generalized epileptic seizure due to aspiration, severe myoclonus and unmanageable saliva, or an undetermined cause. Death can also occur due to aspiration pneumonia, renal failure, or rejection of a renal transplant [Andermann et al 1986, Badhwar et al 2004, Vadlamudi et al 2006, Rubboli et al 2011].
#### Late-Onset AMRF
Disease onset in the fifth or sixth decade has been reported in two Japanese families.
Higashiyama et al [2013] reported one family with two sibs with AMRF without renal failure. The sister presented with myoclonic jerks at age 43 years; her older brother presented with gait difficulties at age 52 years. Both were homozygous for the SCARB2 pathogenic variant c.1385_1390del6insATGCATGCACC.
Fu et al [2014] reported single affected individuals from two other Japanese families, one of whom (Patient 1) had late-onset disease. Patient 1 presented with onset of difficulties going up and down the stairs at age 45 years. Of note, he was homozygous for the same pathogenic variant as the two sibs reported by Higashiyama et al [2013]. Although the two families with the late-onset form are likely related as they originate from the same rural area, the precise relationship is unknown [Hiroshi Doi, 2014, personal communication; Hitoshi Takahashi, June 2014, personal communication]. Of note, Patient 2 reported by Fu et al [2014] presented at age 20 years, was unrelated to Patient 1, and was homozygous for a different SCARB2 pathogenic variant.
#### Specialized Studies
EEG findings [Andermann et al 1986, Badhwar et al 2004]. Background activity may be normal in some patients or show diffuse slowing at 6.5 to 7.5 Hz. Relatively low-voltage spike and spike-wave discharges, rather infrequent, bilaterally synchronous and generalized or confined to the central vertex or both occipital regions, increased by hyperventilation and intermittent photic stimulation, may be present.
Some of the brief spike potentials are difficult to distinguish from muscle potentials except that they are seen at the vertex where there is no muscle artefact. The electromyogram myoclonic potentials are sometimes associated with cerebral potentials and at other times occur independently, suggesting a subcortical origin with a secondary corticoreticular generalization.
Intermittent photic stimulation may produce whole-body myoclonus with multiple spikes in the EEG record associated with slow waves [Andermann et al 1986]. These generalized spike-polyspike-wave bursts can outlast the duration of light stimulation [Rubboli et al 2011].
Myoclonic seizures can be triggered by eye closure and resolve by eye opening [Rubboli et al 2011].
Overnight sleep recording can show fast spikes over the vertex spreading to bilateral frontocentral regions during rapid eye movement (REM) sleep.
Follow up over the course of the disease shows a preserved alpha background activity at disease onset, with rare generalized or focal epileptiform discharges. Over the years, irregular slower theta and delta waves progressively intermix with the alpha waves, and the epileptic activity becomes more frequent [Rubboli et al 2011].
MRI findings. Brain MRI may be normal or show mild diffuse cerebral and cerebellar atrophy [Andermann et al 1986, Badhwar et al 2004, Perandones et al 2012].
Electromyography findings. Nerve conduction analysis can show slowed nerve conduction velocities and prolonged F-waves, consistent with a mixed, mainly demyelinating polyneuropathy [Dibbens et al 2011, Hopfner et al 2011, Rubboli et al 2011].
In one patient, concentric needle electromyography (EMG) was suggestive of chronic anterior horn involvement [Zeigler et al 2014].
Brain histologic findings. A constant and pathognomonic finding is the presence of small and large autofluorescent pigment granules up to 10 µm in size in astrocytes and in certain cells in the meninges. The pigment granules are more prominent in laminae I and II of the cerebral cortex, the globus pallidus and putamen, and the Bergmann astrocytes in the cerebellar cortex; they are not seen in the thalamus, brain stem nuclei, dentate nuclei of the cerebellum, or spinal cord gray matter. The granules are both separate from as well as adjacent to glial cell nuclei, suggesting that at least some were within astrocytes [Andermann et al 1986, Badhwar et al 2004, Berkovic et al 2008].
Neurons contain normal amounts of lipofuscin and no pigment granules [Andermann et al 1986, Badhwar et al 2004]. In two affected individuals of Japanese ancestry extraneuronal brown pigment deposition, exclusively in astrocytic cytoplasm and surrounded by a membrane, was widely scattered throughout the brain [Fu et al 2014].
Click here for information about specialized studies for biologic and histologic findings.
### Genotype-Phenotype Correlations
No clear genotype-phenotype correlation is evident.
Disease severity may vary among affected individuals within a family who have the same pathogenic variants. In some affected individuals, phenotypic variability may be explained by the presence of an additional pathogenic variant in another epilepsy-related gene [He et al 2014].
### Nomenclature
Action myoclonus – renal failure (AMRF) syndrome has been referred to as:
* Familial myoclonus with renal failure
* Progressive myoclonus epilepsy with renal failure
* Epilepsy, progressive myoclonic 4, with or without renal failure, EPM4. However, the presence or absence of renal failure represents only part of the clinical spectrum of AMRF.
The term progressive myoclonus epilepsy (PME) covers a large group of diseases characterized by myoclonus, epilepsy, and progressive neurologic deterioration.
### Prevalence
Exact prevalence figures are not available. To the authors' knowledge, 38 affected individuals from 26 families have been reported to date.
AMRF was first reported in several French-Canadian families [Andermann et al 1986]; it occurs worldwide, including Europe; North, Central and South America; Australia; Asia; and the Middle East.
Families without renal failure have been reported in Italy [Dibbens et al 2009], Spain [Guerrero-López et al 2012], Asia [Higashiyama et al 2013, Fu et al 2014, He et al 2014], and the Middle East [Zeigler et al 2014].
## Differential Diagnosis
At the onset of the disease, three non-progressive conditions should be considered in the differential diagnosis:
* Cortical tremor syndrome. At the onset of fine tremor, cortical tremor syndrome (see Epilepsy, familial adult myoclonic: OMIM Phenotypic Series) should be considered [Ikeda et al 1990, Brown 2004]. Cortical tremor syndrome, also referred to as familial adult myoclonic epilepsy (FAME) and familial cortical myoclonic tremor associated with epilepsy (FCMTE), is characterized by adult-onset cortical myoclonus of the extremities and seizures (mainly generalized tonic-clonic, less frequently myoclonic seizures or complex partial seizures) in 40% of affected individuals. It usually has a favorable outcome.
Cortical tremor syndrome is inherited in an autosomal dominant manner in the majority of families. Five loci have been identified, three with autosomal dominant inheritance [Guerrini et al 2001, Depienne et al 2010, Striano et al 2010, Coppola et al 2011, Crompton et al 2012]. In one family with autosomal dominant inheritance, a heterozygous pathogenic variant in ACMSD has been identified [Martí-Massó et al 2013]. In one family with autosomal recessive inheritance, homozygous CNTN2 pathogenic variants have been identified [Stogmann et al 2013].
* Juvenile myoclonic epilepsy (JME). JME, which has a favorable outcome, should be considered at the onset of myoclonus. Individuals with JME have a normal neurologic examination and the EEG background activity is undisturbed. The myoclonus is not progressive [Zifkin et al 2005, Genton et al 2013].
* Myoclonus-dystonia (DYT11). The association of myoclonus and dystonia suggests DYT11 [Klein 2002]. Onset of myoclonus is usually in the first or second decade of life; the myoclonus is subcortical in origin [Roze et al 2008]; about half of affected individuals have segmental dystonia. No other neurologic features (in particular ataxia and cognitive deficits) are associated. DYT11 is inherited in an autosomal dominant manner. Familial myoclonus-dystonia is associated with pathogenic variants in SGCE [Zimprich et al 2001].
In individuals with a PME phenotype who do not have biallelic SCARB2 pathogenic variants, the following disorders should be considered:
* Unverricht-Lundborg disease (EPM1), also referred to as EPM1A, is a progressive myoclonus epilepsy syndrome with an earlier age of onset and a slower rate of disease progression than AMRF; cognition is normal or mildly reduced [Kälviäinen et al 2008, Genton 2010]. Inheritance is autosomal recessive; biallelic pathogenic variants in CSTB (encoding cystatin B) are causative.
* PRICKLE1-related progressive myoclonus epilepsy with ataxia (EPM1B) is a progressive myoclonus epilepsy-ataxia syndrome that presents in childhood. Ataxia begins at ages 4 to 5 years and evolves to PME with ataxia and mild or no cognitive decline. Impaired upward gaze has been observed in several affected individuals [Berkovic et al 2005, Bassuk et al 2008]. PRICKLE1-related PME with ataxia is inherited in an autosomal recessive manner.
* Progressive myoclonus epilepsy, Lafora type is considered in individuals with visual hallucinations (occipital epilepsy) and cognitive decline. Skin biopsy shows pathognomonic Lafora bodies [Carpenter et al 1974, Carpenter & Karpati 1981]. Inheritance is autosomal recessive. Biallelic pathogenic variants in either EPM2A or NHLRC1 (EPM2B) are causative [Minassian et al 1998, Chan et al 2003].
* EPM5 (OMIM 613832) is characterized by myoclonic seizures, cerebellar signs and deterioration of cognition as well as visual impairment [Bird and Shaw 1978]. Some phenotypic findings may be similar to dentatorubral-pallidoluysian atrophy (DRPLA) [Bird & Shaw 1978, Tsuji 2012]. Inheritance is autosomal dominant; heterozygous pathogenic variants in PRICKLE2 are causative [Tao et al 2011].
* Progressive myoclonic epilepsy and ataxia due to KCNC1 channel mutation B (MEAK) is clinically similar to Unverricht-Lundborg disease. Inheritance is autosomal dominant; a recurrent de novo KCNC1 pathogenic variant, c.959G>A (p.Arg320His) which causes loss of function of KV3.1, a subunit of the KV3 voltage-gated potassium ion channels, is causative [Muona et al 2015].
* Neuronal ceroid-lipofuscinoses (NCL). In adult NCL (ANCL) (formerly called Kufs disease), initial signs and symptoms usually appear around age 30 years (range: teens to >50 years), with death occurring about ten years later. ANCL is clinically and genetically heterogeneous, and is inherited in either an autosomal dominant or autosomal recessive manner. It is distinguished from most other forms of NCL by preserved vision. The two major ANCL phenotypes are type A (the major form) and type B [Berkovic et al 1988].
Note: ANCL type B is not part of the differential diagnosis of AMRF since it is characterized by behavioral abnormalities and dementia which may be associated with motor dysfunction, ataxia, extrapyramidal signs, and suprabulbar (brain stem) signs [Berkovic et al 1988, Smith et al 2013].
ANCL type A is characterized by progressive myoclonic epilepsy with cognitive deterioration, ataxia, and late-occurring pyramidal and extrapyramidal signs. It can be inherited in either an autosomal dominant or autosomal recessive manner. The autosomal dominant forms have intraneuronal granular osmiophilic deposits (GRODs) observed on electron microscopy [Burneo et al 2003, Nijssen et al 2003]. Some autosomal dominant forms are caused by heterozygous pathogenic variants in DNAJC5 [Nosková et al 2011, Cadieux-Dion et al 2013, Cadieux-Dion et al 2014]. The autosomal recessive form is mainly caused by biallelic pathogenic variants in CLN6 [Arsov et al 2011].
Other forms of ANCL type A, associated with visual loss, can result from biallelic pathogenic variants in CLN1 [van Diggelen et al 2001, Ramadan et al 2007], CLN5 [Sleat et al 2009, Xin et al 2010] or GRN [Smith et al 2012]. Inheritance is autosomal recessive.
A juvenile form of NCL with autosomal recessive inheritance and GROD is associated with pathogenic variants in the gene encoding palmitoyl-protein thioesterase (PPT), which are also seen in the infantile form of NCL (CLN1) [Mitchison et al 1998].
* Sialidosis type 1 (OMIM 256550) is characterized by PME with cognitive decline and can be assessed with neuroophthalmologic examination, including electroretinography [Boustany 2013, Mink et al 2013]. Sialidosis type 1 is inherited in an autosomal recessive manner and caused by biallelic pathogenic variants of NEU1 [Bonten et al 2000].
* MERRF (myoclonic epilepsy with ragged red fibers) is a multisystem disorder characterized by myoclonus, which is often the first symptom, followed by generalized epilepsy, ataxia, weakness, and dementia. In individuals with MERRF, blood and cerebrospinal fluid concentrations of lactate and pyruvate are commonly elevated at rest and increase excessively after moderate activity [Bindoff & Engelsen 2012, Finsterer & Zarrouk Mahjoub 2012]. MERRF is caused by pathogenic variants in mtDNA and is transmitted by maternal inheritance
* Gaucher disease type 3, characterized by the presence of primary neurologic disease, may have onset before age two years, but often has a more slowly progressive course, with survival into the third or fourth decade. Saccade initiation failure is a common and early manifestation – suggestive of early dysfunction of supranuclear ocular motor control – and can be detected during induced optokinetic or vestibular nystagmus [Harris et al 1999]. Gaucher disease is inherited in an autosomal recessive manner and is caused by biallelic pathogenic variants in GBA (encoding the enzyme β-glucocerebrosidase) [Tsuji et al 1987, Dahl et al 1988].
* Familial encephalopathy with neuroserpin inclusion bodies (FENIB) (OMIM 604218). Age of onset and clinical manifestations vary considerably. The spectrum of clinical phenotypes ranges from cognitive decline/dementia, dysarthria, and tremors to various forms of refractory epilepsy including progressive myoclonus epilepsy (PME) and focal or generalized seizures. Inheritance is autosomal dominant; heterozygous pathogenic variants in SERPINI1 are causative [Hagen et al 2011].
* DRPLA (dentatorubral-pallidoluysian atrophy). Individuals with juvenile onset (age <20 years) of DRPLA present with PME and associated progressive cognitive deterioration and behavioral changes; whereas those with adult onset (age >20 years) of DRPLA present with ataxia, choreoathetosis, and dementia. DRPLA is relatively more common among the Japanese than in other ethnic populations [Takano et al 1998]. DRPLA is inherited in an autosomal dominant manner and expansion of a CAG trinucleotide/polyglutamine tract in ATN1 is causative [Tsuji 2012].
See Epilepsy, progressive myoclonic: OMIM Phenotypic Series to view genes associated with this phenotype in OMIM.
Charcot-Marie-Tooth neuropathy with focal segmental glomerulonephritis (OMIM 614455) should be considered in persons with peripheral neuropathy and glomerulonephritis [Boyer et al 2011]. Inheritance is autosomal dominant; heterozygous pathogenic variants in INF2 are causative.
## Management
### Evaluations Following Initial Diagnosis
To establish the extent of disease and needs in an individual diagnosed with action myoclonus – renal failure (AMRF) syndrome, the following evaluations are recommended:
* Clinical evaluation including cognitive function and school performance, emotional features, eye movements, coordination, handwriting, walking
* Examination of myoclonus including evaluation at rest, with action, and in response to stimuli
* EEG evaluation including photosensitivity before therapy is initiated, as it is most characteristic before the use of anticonvulsant medication
* Renal function
* Audiogram and brain stem auditory evoked potentials (BAEPs) to assess the possibility of clinical or subclinical sensorineural hearing loss [Rubboli et al 2011, Perandones et al 2012, Perandones et al 2014]
* Nerve conduction velocities (NCV) and needle electromyography (EMG)
* Consultation with a clinical geneticist and/or genetic counselor
### Treatment of Manifestations
Neurologic manifestations. Symptomatic pharmacologic and psychosocial support is the mainstay of care for the neurologic manifestations. Response to treatment is variable and may deteriorate over time, necessitating rehabilitative management.
* Valproic acid, the first drug of choice, diminishes myoclonus and the frequency of generalized seizures.
* Clonazepam may be used as add-on therapy for the treatment of myoclonic seizures.
* Levetiracetam appearss to be effective for both myoclonus and generalized seizures, and is recommended in women of child bearing age.
Note: Lamotrigine is not effective in controlling the myoclonus, and may aggravate myoclonus in some patients [Guerrini et al 1998].
Renal manifestations. Renal insufficiency requires dialysis but response to treatment is poor, and renal transplantation is often necessary.
### Prevention of Secondary Complications
Standard measures for prevention of aspiration pneumonia and sudden unexpected death in epilepsy (SUDEP) should be followed; offering psychosocial support may be helpful.
### Surveillance
Lifelong clinical follow up should include the following:
* Neurologic
* Monitoring of antiepileptic drug treatment (drug levels and clinical assessment of biological effects);
* Periodic assessment of hearing by audiograms and BAEPs and of the peripheral nerves by NCV and needle EMG.
* Renal function monitoring by measurement of: blood pressure; body weight; serum concentrations of creatinine, albumin, and cholesterol; 24-hour urinary protein; and creatinine clearance
### Agents/Circumstances to Avoid
Diphenylhydantoin, carbamazepine, oxcarbazepine, and possibly lamotrigine increase myoclonus and should be avoided in any individual with progressive myoclonic epilepsy (PME), including AMRF.
### Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Pregnancy Management
Some antiepileptic drugs can lead to an increased risk of malformations, growth retardation, or neurodevelopmental disabilities in exposed fetuses. However, when pregnant women experience prolonged seizures during pregnancy, the risk of adverse fetal outcomes is increased. Therefore, it is recommended that women with a known seizure disorder continue to take antiepileptic drugs during pregnancy. Standard measures for prevention of fetopathy should be followed. These include:
* Possible changes of medication prior to pregnancy;
* Spacing of the antiepileptic drugs into four doses a day or taking extended release medications, so that the drug levels do not have significant peaks or troughs;
* Monitoring the dosages and drug levels of antiepileptic drugs during pregnancy and after the delivery.
In addition, folic acid should be prescribed at 1 mg/day for all women of childbearing age and increased to 5 mg/day when planning a pregnancy (ideally 3 months prior to conception) and during the pregnancy, in order to prevent possible neural tube defects and other congenital malformations that can be associated with fetal exposure to antiepileptic drugs.
### Therapies Under Investigation
A trial of enzyme replacement therapy (ERP) with imiglucerase (60 U/kg every two weeks) in two sibs with AMRF for a period of one year did not improve the clinical status. Substrate reduction therapy (SRT) with miglustat (600 mg daily) administered to one of the two sibs resulted in a significant reduction of myoclonus [Chaves et al 2011].
Search Clinical Trials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Action Myoclonus – Renal Failure Syndrome
|
None
| 7,387 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK333437/
| 2021-01-18T21:43:54 |
{"synonyms": []}
|
Primary cutaneous amyloidosis is a form of amyloidosis, a group of conditions in which an abnormal protein (called amyloid) builds up in various organs and tissues throughout the body. In primary cutaneous amyloidosis, specifically, this protein accumulates in the skin. There are three main forms of primary cutaneous amyloidosis:
* Lichen amyloidosis \- multiple itchy, raised spots which are scaly and red/brown in color. This rash generally affects the shins, thighs, feet and forearms.
* Macular amyloidosis \- mild to severely itchy, flat, dusky-brown or greyish colored spots that may come together to form patches of darkened skin. This rash generally appears on the upper back between the shoulder blades, the chest and less commonly, the arms.
* Nodular amyloidosis \- asymptomatic firm bumps that may be pinkish-brown to red in color. This rash may occur on the trunk, limbs, face, and/or genitals.
The exact underlying cause of primary cutaneous amyloidosis is poorly understood. It is sometimes associated with other conditions such as atopic dermatitis, sarcoidosis, and psoriasis. Although most cases occur sporadically in people with no family history of the condition, there are rare familial forms caused by changes (mutations) in the OSMR or IL31RA gene. Treatment is based on the signs and symptoms present in each person and may include surgery to remove amyloid deposits and/or certain medications to relieve itching.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Primary cutaneous amyloidosis
|
c0268397
| 7,388 |
gard
|
https://rarediseases.info.nih.gov/diseases/132/primary-cutaneous-amyloidosis
| 2021-01-18T17:58:11 |
{"mesh": ["C562642"], "omim": ["105250", "613955"], "orphanet": ["137807"], "synonyms": ["Primary localized cutaneous amyloidosis", "PLCA", "Lichen amyloidosis familial", "Amyloidosis familial cutaneous lichen", "Amyloidosis 9", "Amyloidosis IX"]}
|
A number sign (#) is used with this entry because this form of frontotemporal dementia (FTD) is caused by mutation in the gene encoding microtubule-associated protein tau (MAPT; 157140) on chromosome 17q21. Most cases are caused by heterozygous mutation, although rare homozygous mutations have been reported.
Description
Frontotemporal dementia (FTD) refers to a clinical manifestation of the pathologic finding of frontotemporal lobar degeneration (FTLD). FTD, the most common subtype of FTLD, is a behavioral variant characterized by changes in social and personal conduct with loss of volition, executive dysfunction, loss of abstract thought, and decreased speech output. A second clinical subtype of FTLD is 'semantic dementia,' characterized by specific loss of comprehension of language and impaired facial and object recognition. A third clinical subtype of FTLD is 'primary progressive aphasia' (PPA), characterized by a reduction in speech production, speech errors, and word retrieval difficulties resulting in mutism and an inability to communicate. All subtypes have relative preservation of memory, at least in the early stages. FTLD is often associated with parkinsonism or motor neuron disease (MND) resembling amyotrophic lateral sclerosis (ALS; 105400) (reviews by Tolnay and Probst, 2002 and Mackenzie and Rademakers, 2007). Mackenzie et al. (2009, 2010) provided a classification of FTLD subtypes according to the neuropathologic findings (see PATHOGENESIS below).
### Clinical Variability of Tauopathies
Tauopathies comprise a clinically variable group of neurodegenerative diseases characterized neuropathologically by accumulation of abnormal MAPT-positive inclusions in nerve and/or glial cells. In addition to frontotemporal dementia, semantic dementia, and PPA, different clinical syndromes with overlapping features have been described, leading to confusion in the terminology (Tolnay and Probst, 2002). Other terms used historically include parkinsonism and dementia with pallidopontonigral degeneration (PPND) (Wszolek et al., 1992); disinhibition-dementia-parkinsonism-amyotrophy complex (DDPAC) (Lynch et al., 1994); frontotemporal dementia with parkinsonism (FLDEM) (Yamaoka et al., 1996); and multiple system tauopathy with presenile dementia (MSTD) (Spillantini et al., 1997). These disorders are characterized by variable degrees of frontal lobe dementia, parkinsonism, motor neuron disease, and amyotrophy.
Other neurodegenerative associated with mutations in the MAPT gene include Pick disease (172700) and progressive supranuclear palsy (PSP; 601104),
Inherited neurodegenerative tauopathies linked to chromosome 17 and caused by mutation in the MAPT gene have also been collectively termed 'FTDP17' (Lee et al., 2001).
Kertesz (2003) suggested the term 'Pick complex' to represent the overlapping syndromes of FTD, primary progressive aphasia (PPA), corticobasal degeneration (CBD), PSP, and FTD with motor neuron disease. He noted that frontotemporal dementia may also be referred to as 'clinical Pick disease' and that the term 'Pick disease' should be restricted to the pathologic finding of Pick bodies.
### Genetic Heterogeneity of Frontotemporal Lobar Degeneration
Mutations in several different genes can cause frontotemporal dementia and frontotemporal lobar degeneration, with or without motor neuron disease. See FTLD with TDP43 inclusions (607485), caused by mutation in the GRN gene (138945) on chromosome 17q21; FTLD mapping to chromosome 3 (600795), caused by mutation in the CHMP2B gene (609512); inclusion body myopathy with Paget disease and FTD (IBMPFD; 167320), caused by mutation in the VCP gene (601023) on chromosome 9p13; ALS6 (608030), caused by mutation in the FUS gene (137070) on 16p11; ALS10 (612069), caused by mutation in the TARDBP gene (605078) on 1p36; and FTDALS (105550), caused by mutation in the C9ORF72 gene (614260) on 9p.
In 1 family with FTD, a mutation was identified in the presenilin-1 gene (PSEN1; 104311) on chromosome 14, which is usually associated with a familial form of early-onset Alzheimer disease (AD3; 607822).
Clinical Features
Schmitt et al. (1984) reported a family in which 10 individuals had amyotrophic lateral sclerosis, parkinsonism-dementia or both. The proband was a 59-year-old man who died after a 14-year course of an illness characterized by progressive dementia, parkinsonism, and ALS. The affected persons were rather widely separated in the family, suggesting to the authors recessive inheritance 'with genetic epistasis.' The pathologic features consisted particularly of Alzheimer neurofibrillary tangles in many areas.
Wszolek et al. (1992) reported a large kindred in which 32 members in 8 generations had a neurodegenerative disorder characterized by progressive parkinsonism with dystonia, dementia, ocular motility abnormalities, pyramidal tract dysfunction, frontal lobe release signs, perseverative vocalizations, and urinary incontinence. The course was exceptionally 'aggressive'; onset of symptoms and death consistently occurred in the fifth decade. In the 4 patients so studied, positron emission tomographic (PET) studies with labeled 6-fluoro-L-DOPA (6FD) demonstrated markedly reduced striatal uptake of the 6FD. Autopsy findings included severe neuronal loss with gliosis in substantia nigra, pontine tegmentum, and globus pallidus, with less involvement of the caudate and the putamen. There were no plaques, tangles, Lewy bodies, or amyloid bodies. The pedigree was entirely consistent with autosomal dominant inheritance. Wszolek et al. (1992) proposed the designation autosomal dominant parkinsonism and dementia with pallidopontonigral degeneration (PPND). Wijker et al. (1996) stated that the kindred described by Wszolek et al. (1992) contained 34 affected individuals over 9 generations. The onset of the disease varied from 32 to 58 years. Wijker et al. (1996) estimated that the disease penetrance was 15% by age 40, 80% by age 45, and more than 90% after 50.
Delisle et al. (1999) reported 2 brothers from a French family who presented early in the fourth decade with a neurodegenerative disorder characterized by an akinetic rigid syndrome and dementia. There was widespread neuronal and glial tau accumulation in the cortex, basal ganglia, brainstem nuclei, and white matter.
Yamaoka et al. (1996) described FLDEM as characterized by behavioral and neuropsychologic features reflecting frontal lobe dysfunction. The changes in behavior and personality that are observed within this clinical category may not present as a distinct phenotype and may even suggest other diagnoses such as schizophrenia, amyotrophy, depression, or dysphasia among various affected members of a family (Lynch et al., 1994).
Lynch et al. (1994) described 13 affected individuals, 6 of whom were living, in family Mo. The mean age of onset was 45 years. Personality and behavioral changes, including the Kluever-Bucy syndrome, were the first symptoms in 12 individuals. All affected individuals demonstrated rigidity, bradykinesia, and postural instability. Mean duration of the disease was 13 years. Genetic etiology was suspected because of the familial clustering in family Mo, despite their wide geographic distribution. Clinical features of individual family members suggested a variety of unrelated clinical diagnoses. Two members who had died before the study was initiated had been institutionalized and carried the diagnosis of schizophrenia. Five family members had depression or alcoholism as young adults. A clinical diagnosis of amyotrophy was made in another. In retrospect, when all the cases were viewed as a group, there was a common theme. Disinhibition occurred early in the disease course. This was manifested by alcoholism, hyperreligiosity, inappropriate sexual behavior, excessive eating, and shoplifting. Curiously, many exhibited a pattern of hoarding and craving of sweets. Eventually, all affected family members developed frontal lobe dementia, affecting behavior and judgment more than language and praxis, and parkinsonism.
Yamaoka et al. (1996) studied a family in which members of 3 generations (and by implication a fourth earlier generation) suffered from FLDEM. Clinical features were summarized for 13 patients; autopsy information was available for 3. The proband had onset of symptoms at age 52 years. Early difficulties included 'depression,' personality changes, and multiple physical complaints, including difficulty with walking. Family members described the patient as severely amotivational, apathetic, and sometimes explosively irritable. He showed impairments in naming, visuoperception, and executive functions, but the rapid forgetting and apraxia typical of AD were not observed. Brain magnetic resonance imaging was normal. Resting-state fluorodeoxyglucose positron-emission tomography showed reduced uptake in the anterior portion of the frontal and temporal lobes but no diffuse hypometabolism and no reduction of the parietotemporal cortices as is typical in AD. The average age of onset of the disorder in this family was 54.9 years, with a range of 45 to 63 years. The average duration of disease in 5 individuals on whom data were available was 9.2 years. Although impaired memory abilities were reported, problems with judgment and problem solving, perseveration, lack of insight, and poor social awareness were more prominent.
Murrell et al. (1997) described an autosomal dominant presenile dementia affecting 39 individuals in 7 generations. In the affected members of the family, clinical symptoms began at an average age of approximately 48 years. The presenting clinical features included disequilibrium, neck stiffness, dysphagia, and memory loss. As the disease progressed, further cognitive decline, superior gaze palsy, and dystaxia were also observed. The average duration from onset of symptoms to death was approximately 10 years.
Iijima et al. (1999) described a family with presenile dementia in a mother and her 2 sons. Mean age of onset was 35 years. All 3 patients presented with personality changes progressing to impaired cognition and memory, as well as disorientation. Later, they became mute and apathetic. Iijima et al. (1999) suggested that the clinicopathologic findings were different from those usually described with FTDP17, even though they found a ser305-to-asn amino acid substitution in the tau gene (157140.0010; see MOLECULAR GENETICS). They thought that the features in their family resembled those found in sporadic corticobasal degeneration. They pointed to the report by Brown et al. (1996) of a case of familial corticobasal degeneration with similarities to their family.
Wilhelmsen et al. (2004) reported a family in which at least 6 members spanning 2 generations had a neurodegenerative illness comprising frontotemporal dementia and features of amyotrophic lateral sclerosis (FTD-ALS). Four other members were reportedly affected. Frank disease onset was in the sixth decade, with a rapid progression to death within a few years; however, some patients showed frontal and anterior temporal lobe dysfunction from earlier in life. Variable clinical features included personality changes, cognitive decline, and variable motor dysfunction characterized by weakness, dysarthria, hyperreflexia, and/or parkinsonism. Wilhelmsen et al. (2004) emphasized the motor abnormalities in this family and noted that the predilection for ALS, not dementia, first brought the family to neurologic attention.
Doran et al. (2007) reported a large family from Liverpool, England, in which 8 individuals had frontotemporal dementia associated with the MAPT intron 10 +16 mutation (157140.0006). All patients were initially diagnosed with Alzheimer disease because of presentation of memory deficits and word-finding difficulties. Prototypic features of frontotemporal dementia, such as disinhibition and personality changes, were not noted initially. Doran et al. (2007) noted the phenotypic variability of this mutation.
Josephs et al. (2009) suggested that there are 2 distinct subtypes of right temporal variant frontotemporal dementia, in which the right temporal lobe is the most atrophic region on brain imaging. Among 20 individuals with these imaging findings, 12 had the behavioral variant of FTD, and 8 had semantic dementia. In the behavioral variant group, the most common features were personality change and inappropriate behavior, whereas in the semantic dementia group, the most common features were prosopagnosia, word-finding difficulties, comprehension problems, and topographagnosia. Brain imaging also showed that the behavioral variant group had greater volume loss in the frontal lobes compared to the semantic group, whereas the semantic group showed greater fusiform loss. All 8 behavioral variant patients with pathologic/genetic studies showed abnormalities in the tau protein, including 7 with MAPT mutations, whereas all 3 with semantic dementia studied showed abnormalities in TDP43. These findings suggested that there may be 2 subtypes of right temporal variant frontotemporal dementia.
### Neuropathologic Findings
Neuropathologic examination of 6 affected family members by Lynch et al. (1994) demonstrated frontotemporal atrophy and neuronal loss superficial (layer 2) spongiform change, and neuronal loss with gliosis in the substantia nigra and amygdala. Anterior horn cell loss was found in each of the 2 spinal cords examined. One of these was from a person with signs and symptoms of amyotrophy.
Yamaoka et al. (1996) performed full neuropathologic study of 1 member of a family with FLDEM (subject 37), with onset at age 45. Gross examination of the brain showed mild atrophy of the frontal, parietal, and occipital lobes, with moderate atrophy of the temporal lobe. There was severe ventricular dilatation. On microscopic examination, the distribution of cell loss was moderate to severe in the midbrain, amygdala, and entorhinal cortex, with variable involvement in the neocortex. The substantia nigra showed severe neuronal loss and moderate pigment incontinence. Lewy bodies and other inclusions were absent. Limited pathology reports available on 2 other subjects showed neuronal loss and gliosis most prominent in the temporal lobe, the third nerve nucleus, and the substantia nigra. Senile plaques, tangles, and Pick bodies were not seen.
In 9 affected individuals reported by Murrell et al. (1997), neuropathologic studies showed neuronal loss in several areas of the central nervous system, as well as argentophilic tau-immunopositive inclusions in neurons and in oligodendroglia.
Reed et al. (1998) presented the neuropathologic findings in affected members of the PPND kindred reported by Wszolek et al. (1992). Features included abundant ballooned neurons in neocortical and subcortical regions as well as tau-positive inclusions. Electron microscopy showed that the abnormal tau proteins formed flat twisted ribbons similar to those observed in corticobasal degeneration. Reed et al. (1998) concluded that PPND could be subcategorized into the tauopathy group of chromosome 17-linked neurodegenerative disorders.
Hutton et al. (1998) pointed out that most cases of frontotemporal dementia show neuronal and/or glial inclusions that stain positively with antibodies raised against the microtubule-associated protein tau, although the tau pathology varies considerably in both its quantity (or severity) and characteristics. The pathologic heterogeneity among families with FTD was emphasized by McKhann et al. (2001) and by Morris et al. (2001).
Neuropathologic examination of 1 affected family member with FTD-ALS by Wilhelmsen et al. (2004) showed cortical atrophy, atrophy of the hippocampus and amygdala, depigmentation of the substantia nigra and locus ceruleus, and both alpha-synuclein (SNCA; 163890) and tau inclusions. No mutations were identified in the MAPT gene. Protein analysis showed that the insoluble tau consisted predominantly of the 4R/0N isoform. Linkage analysis suggested a disease locus on chromosome 17q between markers D17S1862 and D17S928 (lod score of 2.05), distal to the MAPT gene.
Forman et al. (2006) performed a clinicopathologic assessment of 124 patients with either a clinical or pathologic diagnosis of frontotemporal dementia. Neuropathologic examination showed that 46% had a tauopathy, 29% had FTLD with ubiquitin inclusions, and 17% had findings consistent with Alzheimer disease. Patients with FTLD with ubiquitin inclusions were more likely to present with social and language dysfunction; tauopathies were more commonly associated with an extrapyramidal disorder; and AD was associated with greater deficits in memory and executive function.
Other Features
Boeve et al. (2006) performed polysomnography on 6 affected and 5 at-risk members of the PPND family originally reported by Wszolek et al. (1992). None of the 11 individuals had a history of dream enactment behavior suggesting rapid eye movement (REM) sleep behavior disorder or electrophysiologic features of REM sleep without atonia. Neuropathologic examination of several family members showed severe neuronal loss in the substantia nigra and locus ceruleus, suggesting that these regions are not involved in REM sleep behavior disorder. REM sleep behavior disorder has been described in some patients with parkinsonism and synucleinopathies. By contrast, Boeve et al. (2006) concluded that REM sleep behavior disorder is rare in tauopathies, suggesting differences in the selective vulnerability of brainstem circuits between the synucleinopathies and tauopathies.
Using fluid attenuation inversion recovery (FLAIR) MRI, Frank et al. (2007) detected increased T2 signal and atrophy of the mesial temporal lobes bilaterally in 3 of 4 unrelated patients with the N279K MAPT mutation (157140.0009) and a family history of PPND. One of 3 patients with MRI changes was asymptomatic, as was the patient without detectable MRI changes.
Diagnosis
McKhann et al. (2001) reported on the deliberations of an international work group on the clinical and pathologic diagnosis of FTD and Pick disease. It was emphasized that the clinical course and treatment of patients with FTD are different from those of patients with AD.
Lantos et al. (2002) characterized the neuropathologic findings of 12 brains with the intronic tau 10 +16 mutation (157140.0006). They found that the lesions varied considerably in type, distribution, and severity, both between and within families, but that the hallmark lesions are tau-positive inclusions in neuronal and glial cells. Due to the variable nature of the pathologic findings, the authors suggested that definitive diagnosis requires clinical symptomatology, family history, and molecular genetics.
Mendez et al. (2007) evaluated the diagnosis and 2-year follow-up of 134 patients with suspected FTD. At 2 years, 63 patients were diagnosed with FTD, and 71 had other conditions. On initial assessment, 17.2% of patients met all 5 core criteria for the diagnosis: insidious onset and gradual progression, decline in social interpersonal conduct, impaired regulation of personal conduct, emotional blunting, and loss of insight. The positive predictive value for these criteria was 100%, but the negative predictive value was only 64% owing to many false-positives. Evidence of frontotemporal changes on neuroimaging, including MRI, SPECT, and PET scans were more sensitive (63.5 to 90.5%), but less specific (70.4 to 74.6%). Significant worsening in naming and executive function on serial neuropsychologic tests supported the diagnosis. Mendez et al. (2007) emphasized the difficulty in early diagnosis of FTD due to the variable presentation, and suggested that neuroimaging studies in addition to consensus criteria be used for more accurate diagnosis.
Cairns et al. (2007) provided a report of the consensus statement for neuropathologic diagnostic and nosologic criteria from the Consortium for Frontotemporal Lobar Degeneration.
### Differential Diagnosis
Lynch et al. (1994) commented on personality changes similar to those seen in Pick disease as well as in other types of frontal lobe dementia. However, nigral and anterior horn degeneration distinguished the disorder in the Mo family from classic Pick disease. The pathologic features distinguished disinhibition-dementia-parkinsonism-amyotrophy complex from the ALS-parkinsonism-dementia complex of Guam (105500). The late amyotrophy seen in 2 of the affected individuals and the early personality changes seen in 12 of the 13 affected individuals were thought to distinguish the disorder from parkinsonism-dementia with pallidopontonigral degeneration.
Inheritance
In the pedigree described by Lynch et al. (1994), transmission was from females to either females or males; there was no opportunity for male-to-male transmission. In cases where there is familial aggregation, FLDEM appears to be inherited as an autosomal dominant disorder with age-dependent penetrance (Yamaoka et al., 1996).
Goldman et al. (2005) analyzed the family histories of 269 probands with various forms of frontotemporal dementia. The cohort included 99 patients diagnosed with FTD, 27 with FTD-ALS, 53 with semantic dementia, 29 with progressive nonfluent aphasia, 18 with progressive supranuclear palsy, and 43 with corticobasal degeneration. Those with FTD-ALS showed the highest overall positive family history (59.2%), whereas those with semantic dementia showed the lowest positive family history (17%). The pattern of inheritance in all cases was consistent with autosomal dominant.
Pathogenesis
Several neurodegenerative diseases are characterized by the presence of abundant neurofibrillary lesions within certain regions of the brain. These lesions consist of abnormal filaments that are made of microtubular-associated protein tau (MAPT) in the hyperphosphorylated state. The most common of these disorders is Alzheimer disease, in which tau-positive deposits are found in neurofibrillary tangles, neuropil threads, and neurites of plaques. Lesions made of hyperphosphorylated tau similar to those found in AD are present in Down syndrome (190685), Niemann-Pick disease type C (257220), Gerstmann-Straussler-Scheinker disease (137440), prion protein amyloid angiopathy (see 176640), etc.
Spillantini et al. (1997) described an apparently 'new' familial disease with autosomal dominant inheritance that is characterized by an abundant and widespread tau pathology in both nerve cells and glial cells in the absence of beta-amyloid deposits. They named the condition 'familial multiple system tauopathy with presenile dementia' (MSTD). The tau deposits were in the form of twisted filaments that differed in diameter and periodicity from the paired helical filaments of Alzheimer disease. They stained by both phosphorylation-independent and -dependent anti-tau antibodies. Moreover, tau immunoreactivity coexisted with heparan sulfate in affected neurons and glial cells. Tau protein extracted from filaments of familial MSTD showed a minor 72-kD band and 2 major bands of 64 and 68 kD that contained mainly hyperphosphorylated 4-repeat tau isoforms of 383 and 412 amino acids. Some clinical overlap was noted with progressive supranuclear palsy (601104) and corticobasal degeneration, both conditions in which tau-positive neurofibrillary lesions are found. However, they considered MSTD to be distinct from either of these disorders.
Van Leeuwen et al. (2006) detected aberrant frameshifted proteins, APP+1 (APP; 104760) and UBB+1 (UBB; 191339), within the neuropathologic hallmarks of Alzheimer disease and other MAPT-related dementias, including Pick disease, progressive supranuclear palsy, and less commonly frontotemporal dementia. Van Leeuwen et al. (2006) postulated that accumulation of APP+1 and UBB+1, which represents defective proteasome function, contributes to various forms of dementia.
Botella-Lopez et al. (2006) found increased levels of a 180-kD reelin (RELN; 600514) fragment in CSF from 19 patients with AD compared to 11 nondemented controls. Western blot and PCR analysis confirmed increased levels of reelin protein and mRNA in tissue samples from the frontal cortex of AD patients. Reelin was not increased in plasma samples, suggesting distinct cellular origins. The reelin 180-kD fragment was also increased in CSF samples of other neurodegenerative disorders, including frontotemporal dementia, PSP, and PD.
Neumann et al. (2006) identified TDP43 as the major disease protein in both ubiquitin-positive, tau-, and alpha-synuclein-negative FTLD and amyotrophic lateral sclerosis (see 105400). Pathologic TDP43 is hyperphosphorylated, ubiquitinated, and cleaved to generate C-terminal fragments and was recovered only from affected central nervous system regions, including hippocampus, neocortex, and spinal cord. Neumann et al. (2006) concluded that TDP43 represents the common pathologic substrate linking these neurodegenerative disorders.
Mackenzie et al. (2009, 2010) provided recommendations for a classification of FTLD subtypes according to the neuropathologic findings. The 2 main neuropathologic subtypes of FTLD are those with tau-positive inclusions (FTLD-tau), caused by MAPT mutations, and those with ubiquitinated inclusions, formerly known as FTLDU. FTLDU has been found to be heterogeneous, with most cases specifically due to TDP43 (TARDBP; 605078)-positive inclusions. Mutations in the TARDBP, GRN, VCP, and TARDBP genes can all result in FTLD with TDP43-positive inclusions. Two further subtypes include FTLD-FUS (608030), characterized by FUS-positive inclusions and FTLD-UPS (600795), characterized by inclusions with immunoreactivity to the ubiquitinated proteasome system. Mackenzie et al. (2010) emphasized that this classification is based on neuropathology and does not necessarily presuppose a primary role of the signature protein in pathogenesis.
Mapping
Lynch et al. (1994) performed linkage analysis in the Mo family with microsatellite polymorphisms associated with HOX2B, giving a maximum lod score of 3.03 at theta = 0.0, and with GP3A, giving a maximum lod score of 3.28 at theta = 0.0. This localized the disorder to chromosome 17q21-q23. By linkage studies, Wilhelmsen et al. (1994) mapped the disinhibition-dementia-parkinsonism-amyotrophy complex locus in this family to a 12-cM (sex averaged) region between D17S800 and D17S787 on 17q21-q22.
In the large kindred with PPND described by Wszolek et al. (1992), Wijker et al. (1996) found linkage to chromosome 17q21 (maximum lod score of 9.08 at marker D17S958). Multilocus analysis positioned the disease gene in a region of approximately 10 cM between D17S250 and D17S943. Wijker et al. (1996) suggested that PPND and DDPAC may originate from mutations in the same gene.
In a family with FLDEM studied at Duke University and referred to as DUK1684, Yamaoka et al. (1996) demonstrated linkage to 17q21 with a multipoint location score of 5.52. Yamaoka et al. (1996) suggested that FLDEM, DDPAC, and PPND are allelic disorders.
In 3 unrelated families with autosomal dominant frontotemporal dementia, Heutink et al. (1997) reported linkage to markers in 17q21-q22, with a maximum lod score of 4.70 at theta = 0.05 with marker D17S932. The disorder in 1 of these families had previously been reported as hereditary Pick disease, inappropriately in the view of the authors, because there was no histologic evidence of Pick bodies. They recommended that the term Pick disease be reserved for those cases of frontotemporal dementia with histologic Pick bodies.
Spillantini et al. (1997) stated that preliminary results of a genomic screen suggested that MSTD is linked to 17q21, the same region where the tau gene localizes. They noted that frontotemporal dementia with parkinsonism had been linked to chromosome 17 in unpublished studies.
In the 7-generation family studied by Murrell et al. (1997), a limited genomic screen by use of DNA samples from 28 family members localized the gene for this disorder to a 3-cM region on chromosome 17, between markers THRA1 (190120) (which maps to 17q11.2) and D17S791. Other disorders that map to the same region include DDPAC/FLDEM, pallidopontonigral degeneration, and familial progressive subcortical gliosis (221820). All of these disorders may be allelic, though they do show some differences in clinical and pathologic features.
According to Hutton et al. (1998), 13 families had been described with autosomal dominant frontotemporal dementia with parkinsonism linked to chromosome 17; they symbolized the disorder FTDP17 and stated that the same disorder has historically been termed Pick disease. In addition to those already mentioned, families were reported by Wilhelmsen et al. (1994), Wijker et al. (1996), Foster et al. (1997), Baker et al. (1997), and Dark (1997).
In a genomewide association study in 1,713 individuals of European ancestry with Parkinson disease and 3,978 controls, followed by replication in 3,361 cases and 4,573 controls, Simon-Sanchez et al. (2009) identified association with the MAPT gene (157140) on 17q21 (rs393152, OR = 0.77, p = 1.95 x 10(-16)).
Molecular Genetics
### Mutations in the MAPT Gene
Hutton et al. (1998) sequenced the MAPT gene in 13 families with FTDP17 and identified 3 missense mutations (gly272 to val, 157140.0002; pro301 to leu, 157140.0001; and arg406 to trp, 157140.0003) and 3 mutations in the 5-prime splice site of exon 10. The splice site mutations all destabilized a potential stem-loop structure that is probably involved in regulating the alternative splicing of exon 10. This causes more frequent use of the 5-prime splice site and an increased proportion of tau transcripts that include exon 10. The increase of exon 10+ mRNA was expected to increase the proportion of tau transcripts containing 4 microtubule-binding repeats, which is consistent with the neuropathology described in families with FTDP17. In the kindred studied by Wilhelmsen et al. (1994) and Lynch et al. (1994), Hutton et al. (1998) demonstrated a splice donor site mutation in the MAPT gene (157140.0004).
In affected members of the PPND kindred reported by Wszolek et al. (1992), Clark et al. (1998) identified a heterozygous mutation in the MAPT gene (N279K; 157140.0009). Delisle et al. (1999) identified the N279K mutation in 2 French brothers with parkinsonism and dementia. Tsuboi et al. (2002) compared the clinical phenotypes of the original American family reported by Wszolek et al. (1992) and the French family reported by Delisle et al. (1999). The families shared many features, including autosomal dominant inheritance, age of onset and disease duration, parkinsonism, personality changes, dementia, pyramidal signs, and eye movement abnormalities.
In 1 of the families initially reported by Lanska et al. (1994) as having early-onset progressive frontal lobe dementia associated with prominent subcortical gliosis (221820), Petersen et al. (1995) found linkage to chromosome 17q21-q22. Although Petersen et al. (1995) originally described diffuse prion plaques and protease-resistant prion fragments in members of 1 of the families reported by Lanska et al. (1994), no mutations were identified in the PRNP gene. Gambetti (1997) later excluded prion pathology upon revisiting this family. Goedert et al. (1999) identified a heterozygous mutation in the MAPT gene (157140.0006) in affected members of this family, indicating a diagnosis of tau-related frontotemporal dementia. Neuropathologic examination showed hyperphosphorylated tau in both neurons and glial cells. Ultrastructurally, the tau filaments were characterized by wide twisted ribbons made of 4-repeat tau isoforms. Goedert et al. (1999) noted that phenotypic heterogeneity associated with MAPT mutations has led to classification of related diseases into distinct entities.
Seelaar et al. (2008) found a family history consistent with autosomal dominant inheritance in 98 (27%) of 364 probands with frontotemporal dementia. Among the familial cases, mutations in the GRN and MAPT gene were identified in 6% and 11%, respectively. Those with GRN mutations had a higher mean age at onset (61.8 years) compared to those with MAPT mutations (52.4). Neuropathologic findings, when available, were consistent with genetic analysis.
Among 225 patients with a diagnosis of FTLD, Rohrer et al. (2009) found that 41.8% had some family history of the disorder, although only 10.2% had a clear autosomal dominant history. Those with the behavioral variant of the disorder were more likely to have a positive family history than those with the language syndromes. Mutations in the MAPT and GRN genes were found in 8.9% and 8.4% of the cohort, respectively.
### Mutation in the PSEN1 Gene
Raux et al. (2000) reported 6 members of a family with early-onset frontotemporal dementia, confirmed by imaging studies, with autosomal dominant inheritance. In 2 patients available for testing, the authors found a novel heterozygous mutation in the presenilin-1 gene (L113P; 104311.0023).
### Genetic Modifiers and Susceptibility Alleles
Short et al. (2002) determined the tau haplotype frequencies and APOE (107741) allele frequencies in 63 patients with sporadic disease categorized by clinical subtype of frontotemporal lobar degeneration (FTLD). The clinical subtypes are determined by the distribution of pathologic findings: in the frontal lobe, frontotemporal dementia (FD) and progressive nonfluent aphasia (PA), and in the temporal lobes, anomic aphasia (AA) in the left, and visual aphasia in the right. No tau mutations were found. Short et al. (2002) found that the APOE4 allele and the tau H2 haplotype were more common in patients with AA than FD. The tau H2 haplotype was more common in APOE4-positive patients with AA and less common in APOE4-negative patients with FD. Thus, there are genetic differences between the clinical subtypes of FTLD. In addition, the increase of tau H2 frequency in patients with an APOE4 allele and AA suggested that there may be an interaction between these 2 genes, resulting in a specific clinical phenotype.
Verpillat et al. (2002) found that the H1/H1 tau genotype was significantly overrepresented in 100 patients with frontotemporal dementia compared to controls (odds ratio for H1/H1 = 1.95). In addition, there was a significant negative effect in carriers of both the H1/H1 genotype and the APOE2 allele.
Verpillat et al. (2002) determined the APOE genotype frequencies in 94 unrelated patients with frontotemporal dementia and 392 age- and sex-matched controls without cognitive deficits or behavioral disturbances (after excluding 6 patients with autosomal dominant inheritance and mutation in the MAPT gene). Homozygosity for the E2E2 genotype was significantly associated with frontotemporal dementia (odds ratio = 11.3, P = 0.033, exact test) but based on very few subjects (3 patients and 1 control). The result was even more significant in the group with a positive familial history (odds ratio = 23.8, P = 0.019, exact test). For the metaanalysis of the APOE polymorphism in frontotemporal dementia, Verpillat et al. (2002) pooled 10 case-control studies with available genotype or allele information (total of 364 patients and 2,671 controls), but the E2E2 genotype did not reach statistical significance. Because of heterogeneity, Verpillat et al. (2002) analyzed on one hand the neuropathologically-confirmed studies and on the other hand the clinical-based studies. A significant increase in the E2 allele frequency was found in the neuropathologically-confirmed patients, and heterogeneity disappeared (Mantel-Haenszel statistics). The authors concluded that the APOE E2 allele may be a risk factor for frontotemporal dementia, but that the data should be interpreted with caution due to the rarity of the E2E2 genotype.
Borroni et al. (2005) found no association between FTD and the H1 or H2 MAPT haplotypes among 86 patients with FTD and 50 control individuals. However, the findings suggested an earlier age at onset in patients carrying an H2 allele.
Among 32 patients with a clinical diagnosis of frontotemporal dementia, including 15 patient with primary progressive aphasia, Acciarri et al. (2006) found increased frequency of the APOE E2 and E4 alleles and significantly decreased frequency of the E3 allele compared to 87 control individuals. The E2E4 genotype in particular was significantly associated with primary progressive aphasia.
Genotype/Phenotype Correlations
Among 22 patients with FTLD due to a MAPT mutation, Whitwell et al. (2009) found different patterns of gray matter atrophy using MRI voxel-based morphometry. All patients showed gray matter loss in the anterior temporal lobes, with varying degrees of involvement of the frontal and parietal lobes. Within the temporal lobe, individuals with the IVS10+16 IVS10+16 (157140.0006), IVS10+3, N279K (157140.0009), or S305N (157140.0010) mutations showed gray matter loss particularly affecting the medial temporal lobes, including the hippocampus and amygdala. These mutations are all predicted to influence the alternative splicing of MAPT pre-mRNA, resulting in increased 4R tau isoforms. In contrast, patients with the P301L (157140.0001) or V337M (157140.0008) mutations showed gray matter loss particularly affecting the inferior and lateral temporal lobes, with a relative sparing of the medial temporal lobe. P301L and V337M mutation carriers also showed gray matter loss in the basal ganglia. These mutations are predicted to affect the structure and functional properties of the tau protein, which are more prone to aggregation. The different patterns suggested a potential difference in mutant protein function resulting from different pathogenic mutations.
Animal Model
To model tauopathies, Ishihara et al. (1999) overexpressed the smallest human tau isoform in the central nervous system of transgenic mice. These mice acquired age-dependent central nervous system pathology, including insoluble, hyperphosphorylated tau and argyrophilic intraneuronal inclusions formed by tau-immunoreactive filaments. Inclusions were present in cortical and brainstem neurons but were most abundant in spinal cord neurons, where they were associated with axon degeneration, diminished microtubules, and reduced axonal transport in ventral roots, as well as spinal cord gliosis and motor weakness. These transgenic mice recapitulated key features of tauopathies and provided models for elucidating mechanisms underlying diverse tauopathies.
Noting that earlier mouse models had focused on neuronal tau pathology, Higuchi et al. (2002) generated transgenic mice overexpressing human tau in glia as well as in neurons. The animals showed accumulation of abnormal tau aggregates in glial cells with progressing age, loss of neurons and glial cells, disruption of myelin sheaths, and progressive motor disturbances such as weakness and dystonia.
INHERITANCE \- Autosomal dominant NEUROLOGIC Central Nervous System \- Frontal lobe dementia \- Language impairment \- Word-finding difficulties \- Decrease in abstract thinking \- Motor symptoms may be present \- Parkinsonism \- Amyotrophic lateral sclerosis \- Cortical and subcortical neuronal loss in the frontal and temporal regions \- Tau-positive inclusions may be found \- Ubiquitin-positive inclusions \- Primitive reflexes (palmomental, snout, glabellar) Behavioral Psychiatric Manifestations \- Personality changes \- Lack of motivation \- Inappropriate laughter \- Apathy \- Irritability \- Disinhibition \- Kluver-Bucy syndrome \- Inappropriate sexual behavior \- Hyperphagia \- Hyperoralia MISCELLANEOUS \- Mean age at onset 45 years \- Highly variable phenotype that includes several subtypes (see, e.g., 607485 , 601104 ) \- Genetic heterogeneity (see, e.g., 600795 , 105550 ) \- Most cases do not have mutations in the MAPT gene, but map to chromosome 17q MOLECULAR BASIS \- Caused by mutation in the microtubule-associated tau protein gene (MAPT, 157140.0001 ) \- Caused by mutation in the presenilin-1 gene (PSEN1, 104311.0023 ) ▲ Close
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*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
FRONTOTEMPORAL DEMENTIA
|
c0338462
| 7,389 |
omim
|
https://www.omim.org/entry/600274
| 2019-09-22T16:16:23 |
{"doid": ["9255"], "mesh": ["D057180"], "omim": ["600274"], "icd-9": ["331.1"], "icd-10": ["G31.0"], "orphanet": ["100069", "100070", "293848", "282", "275864"], "synonyms": ["Alternative titles", "FRONTOTEMPORAL LOBAR DEGENERATION WITH TAU INCLUSIONS", "FTLD WITH TAU INCLUSIONS", "DEMENTIA, FRONTOTEMPORAL, WITH PARKINSONISM", "FRONTOTEMPORAL DEMENTIA WITH PARKINSONISM", "FRONTOTEMPORAL LOBE DEMENTIA", "FTDP17", "MULTIPLE SYSTEM TAUOPATHY WITH PRESENILE DEMENTIA", "DISINHIBITION-DEMENTIA-PARKINSONISM-AMYOTROPHY COMPLEX", "WILHELMSEN-LYNCH DISEASE", "PALLIDOPONTONIGRAL DEGENERATION"]}
|
Excessive fat build-up in the liver not caused by alcohol use
Non-alcoholic fatty liver disease
Other namesNAFLD, metabolic (dysfunction) associated fatty liver disease, MAFLD[1]
Stages of non-alcoholic fatty liver disease, progressing from healthy, to steatosis (fat accumulation), inflammation, fibrosis and cirrhosis.
SpecialtyHepatology
SymptomsAsymptomatic, liver dysfunction
ComplicationsCirrhosis, liver cancer, liver failure, cardiovascular disease[2][3]
DurationLong term
TypesNon-alcoholic fatty liver (NAFL),
non-alcoholic steatohepatitis (NASH)[3][4]
CausesGenetic, environmental
Risk factorsObesity, metabolic syndrome, type 2 diabetes mellitus, liver disease
Diagnostic methodLiver biopsy
TreatmentWeight loss (diet and exercise)[3][5]
PrognosisDepends on type[6]
Frequency24% in worldwide population, 80% in obese, 20% in normal-weight
DeathsNASH: 2.6% risk of death per year[4]
Non-alcoholic fatty liver disease (NAFLD), also known as metabolic (dysfunction) associated fatty liver disease (MAFLD), is excessive fat build-up in the liver without another clear cause such as alcohol use.[2][3] There are two types; non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH), with the latter also including liver inflammation.[3][4][6] Non-alcoholic fatty liver disease is less dangerous than NASH and usually does not progress to NASH or liver cirrhosis.[3] When NAFLD does progress to NASH, it may eventually lead to complications such as cirrhosis, liver cancer, liver failure, cardiovascular disease.[3][7]
Obesity and type 2 diabetes are strong risk factors for NAFLD.[5] Other risks include being overweight, metabolic syndrome (defined as at least three of the five following medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum HDL cholesterol), a diet high in fructose, and older age.[6] NAFLD and alcoholic liver disease are types of fatty liver disease.[6] Obtaining a sample of the liver after excluding other potential causes of fatty liver can confirm the diagnosis.[2][5][6]
Treatment for NAFLD is weight loss by dietary changes and exercise.[4][8][9] There is tentative evidence for pioglitazone and vitamin E;[3][10][11] bariatric surgery can improve or resolve severe cases.[8][12] Those with NASH have a 2.6% increased risk of dying per year.[4]
NAFLD is the most common liver disorder worldwide and is present in approximately 25% of the world's population.[13] It is also very common in developed nations, such as the United States, and affected about 75 to 100 million Americans in 2017.[14][15][16][17] Over 90% of obese, 60% of diabetic, and up to 20% normal-weight people develop it.[18][19] NAFLD is the leading cause of chronic liver disease[17][18] and the second most common reason for liver transplantation in the US and Europe as of 2017.[8] NAFLD affects about 20 to 25% of people in Europe.[12] In the United States, estimates suggest between 30 and 40% of adults have NAFLD, and about 3 to 12% of adults have NASH.[3] The annual economic burden was approximately US$103 billion in the US in 2016.[18]
## Contents
* 1 Definition
* 2 Signs and symptoms
* 2.1 Comorbidities
* 3 Risk factors
* 3.1 Genetics
* 3.2 Diet
* 4 Pathophysiology
* 4.1 Fructose consumption
* 4.2 Insulin resistance
* 4.3 Dysbiosis
* 5 Diagnosis
* 5.1 Blood tests
* 5.2 Imaging
* 5.3 Liver biopsy
* 6 Management
* 6.1 Lifestyle
* 6.1.1 Diet
* 6.1.2 Physical activity
* 6.2 Medication
* 6.3 Surgery
* 6.4 Screening
* 6.5 Transplantation
* 6.6 Related complications
* 7 Prognosis
* 8 Epidemiology
* 9 History
* 10 Society and culture
* 10.1 Political recommendations
* 10.2 Lobbying
* 11 Children
* 12 Research
* 12.1 Diagnosis and biomarkers
* 12.2 Medication development
* 13 See also
* 14 References
* 15 External links
## Definition[edit]
An abnormal accumulation of fat in the liver in the absence of secondary causes of fatty liver, such as significant alcohol use, viral hepatitis, or medications that can induce fatty liver characterizes non-alcoholic fatty liver disease (NAFLD).[13] The term NAFLD encompasses a continuum of liver abnormalities, from non-alcoholic fatty liver (NAFL, simple steatosis) to non-alcoholic steatohepatitis (NASH). These diseases begin with fatty accumulation in the liver (hepatic steatosis). A liver can remain fatty without disturbing liver function (NAFL), but by various mechanisms and possible insults to the liver, it may also progress into non-alcoholic steatohepatitis (NASH), a state in which steatosis is combined with inflammation and sometimes fibrosis (steatohepatitis). NASH can then lead to complications such as cirrhosis and hepatocellular carcinoma.[2][4][20]
A new name, metabolic dysfunction associated fatty liver disease, was proposed after 70% of a panel of experts expressed support for this name.[1]
## Signs and symptoms[edit]
Play media
Overview of non-alcoholic fatty liver disease
People with NAFLD often have no noticeable symptoms, and NAFLD is often only detected during routine blood tests or unrelated abdominal imaging or liver biopsy.[4][20] In some cases, NAFLD can cause symptoms related to liver dysfunction such as fatigue, malaise, and dull right-upper-quadrant abdominal discomfort. Mild yellow discoloration of the skin may occur, although this is rare.[21] NASH can severely impair liver function, leading to cirrhosis, liver failure, and liver cancer.[4]
### Comorbidities[edit]
NAFLD is strongly associated with or caused by type 2 diabetes, insulin resistance, and metabolic syndrome (defined as at least three of the five following medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein). It is also associated with hormonal disorders (panhypopituitarism, hypothyroidism, hypogonadism, polycystic ovary syndrome), persistently elevated transaminases, increasing age and hypoxia caused by obstructive sleep apnea, with some of these conditions predicting disease progression.[2][5][7][11][14][18][22]
The majority of normal-weight people affected by NAFLD ("lean NAFLD") have impaired insulin sensitivity, are sedentary, and have increased cardiovascular disease risk and increased liver lipid levels. These are the consequences of a decreased capacity for storing fat and reduced mitochondrial function in adipose tissue and increased hepatic de novo lipogenesis.[5][18]
## Risk factors[edit]
### Genetics[edit]
Two-thirds of families with a history of diabetes type 2 report more than one family member having NAFLD. There is a higher risk of fibrosis for family members where someone was diagnosed with NASH.[20] Asian populations are more susceptible to metabolic syndrome and NAFLD than their western counterparts.[5] Hispanic persons have a higher prevalence of NAFLD than white individuals, whereas the lowest prevalence is observed in black individuals.[18] NAFLD is twice as prevalent in men compared to women,[4] which might be explained by lower levels of estrogen in men.[23]
Genetic variations in two genes are associated with NAFLD: non-synonymous single-nucleotide polymorphisms (SNPs) in PNPLA3 and TM6SF2. Both correlate with NAFLD presence and severity, but their roles for diagnosis remain unclear.[18][24] Although NAFLD has a genetic component, the American Association for the Study of Liver Diseases (AASLD) does not recommend screening family members as there is not enough confirmation of heritability,[4] although there is some evidence from familial aggregation and twin studies.[18]
### Diet[edit]
According to the Asia-Pacific Working Group (APWG) on NAFLD, overnutrition is a major factor of NAFLD and NASH, particularly for lean NAFLD.[5] Diet composition and quantity, in particular omega-6 fatty acid and fructose, have important roles in disease progression from NAFL to NASH and fibrosis.[25][26] Choline deficiency can lead to the development of NAFLD.[27]
## Pathophysiology[edit]
The primary characteristic of NAFLD is the accumulation of lipids in the liver, largely in the form of triglycerides.[13] However, the mechanisms by which triglycerides accumulate and the reasons that accumulation can lead to liver dysfunction are complex and incompletely understood.[13][28][29][30] NAFLD can include steatosis along with varied signs of liver injury: either lobular or portal inflammation (a form of liver injury) or ballooning degeneration. Similarly, NASH can include histological features such as portal inflammation, polymorphonuclear cell infiltrates, Mallory bodies, apoptotic bodies, clear vacuolated nuclei, microvesicular steatosis, megamitochondria, and perisinusoidal fibrosis.[12] NASH increases hepatocyte death via apoptosis or necroptosis is increased in NASH compared with simple steatosis, and inflammation is a hallmark of NASH.[24]
One debated mechanism proposes that hepatic steatosis progresses to steatosis with inflammation following some further injury, or second hit. Oxidative stress, hormonal imbalances, and mitochondrial abnormalities are potential causes of this "second hit" phenomenon.[20] A further nutrigenomics model named multiple hit extends the second hit model, suggesting that multiple disease biomarkers and factors such as genes and nutrition influence NAFLD and NASH progression. This model attempts to use these factors to predict the impact of lifestyle changes and genetics for the evolution of the NAFLD pathology.[31] Many researchers describe NAFLD as a multisystem disease, as it impacts and is influenced by organs and regulatory pathways other than the liver.[32][33][34]
The accumulation of senescent cells in the liver is seen in persons with NAFLD.[35] In mice, liver senescent hepatocytes result in increased liver fat deposition.[35] Treatment of NAFLD mice with senolytic agents has been shown to reduce hepatic steatosis.[35]
### Fructose consumption[edit]
Non-alcoholic and alcoholic fatty liver disease share similar histological features, which suggests that they might share common pathogenic pathways. Fructose can cause liver inflammation and addiction similarly to ethanol by using similar metabolic pathways, unlike glucose. Therefore, some researchers argue that non-alcoholic and alcoholic fatty liver diseases are more alike than previously thought.[25][36] Furthermore, high fructose consumption promotes fat accumulation in the liver by stimulating de novo lipogenesis in the liver and reducing the beta-oxidation of fat.[13] Unlike the sugar glucose, the enzyme fructokinase rapidly metabolizes fructose. This leads to a decreased level of intracellular adenosine triphosphate (ATP).[13] The decrease in ATP increases oxidative stress and impairments in proper protein synthesis and mitochondrial function in the liver.[13]
### Insulin resistance[edit]
Insulin resistance contributes to the accumulation of toxic fat in the liver in several ways. First, it promotes the release of free fatty acids (FFAs) from adipose tissue into the blood. Typically, adipose tissue stores lipids in the form of triglycerides, slowly releasing them into the bloodstream when insulin is low. In insulin-resistant adipose tissue, such as in people with obesity and type 2 diabetes, more triglycerides are broken down into FFAs and released into the bloodstream, promoting uptake by the liver.[13] Second, insulin promotes the production of new FFAs in the liver via de novo lipogenesis; this production of liver fats continues to be stimulated by insulin, even when other tissues are insulin-resistant.[13] These FFAs are combined back into triglycerides in the liver, forming the major constituent of the accumulated fat in the liver.[13] The three sources of free fatty acids that contribute to liver triglyceride accumulation include FFAs circulating in the bloodstream (59%), FFAs derived from carbohydrates such as fructose and glucose (26%), and diet (14%).[13] Despite the accumulation of triglycerides in the liver, they are not directly toxic to liver tissue.[13] Instead, alteration of the profile of the other lipid subtypes present in the liver, such as diacylglycerols, phospholipids, ceramides, and free cholesterol, have a more significant role in the pathogenesis of NAFLD.[13]
Once NAFLD progresses in severity to the point of NASH, this promotes further insulin resistance in the adipose tissue and liver, which results in a harmful cycle of insulin resistance, liver fat accumulation, and inflammation.[13] Adipose tissue dysfunction also decreases secretion of the insulin-sensitizing adipokine adiponectin in people with NAFLD.[13] Adiponectin has several properties that protect the liver.[13] These properties include improved liver fat metabolism, decreased de novo lipogenesis, decreased glucose production in the liver, anti-inflammatory properties, and anti-fibrotic properties.[13] Skeletal muscle insulin resistance may also play a role in NAFLD. Insulin-resistant skeletal muscle is not as efficient at taking up glucose from the bloodstream after a meal.[13] This inefficient glucose uptake promotes the redistribution of consumed carbohydrates from glucose destined for use in glycogen stores in the skeletal muscles to being used as a substrate for de novo lipogenesis in the liver.[13]
### Dysbiosis[edit]
Disruptions in the intestinal microbiota seem to influence NAFLD risk in several ways. People with NASH can have elevated levels of blood ethanol and proteobacteria (which produce alcohol), with dysbiosis proposed as a mechanism for this elevation.[37] Alterations in the composition of the intestinal microbiota may influence NAFLD risk in several ways. These changes appear to increase the permeability of intestinal tissue, thereby facilitating increased liver exposure to harmful substances (e.g., translocated bacteria, bacterial toxins, and inflammatory chemical signals). The increased transport of these harmful substances to the liver promotes liver inflammation, enhances nutrient and calorie absorption, and alters choline metabolism.[37][38][39] Higher levels of intestinal bacteria that produce butyrate may be protective.[37]
Excessive macronutrient intake contributes to gut inflammation and perturbation of homeostasis, and micronutrients may also be involved.[40] In addition to reducing weight and risk factors, lifestyle changes may prompt positive changes in the gut microbiota.[41] In particular, diet diversity may play a role that was overlooked in animal studies, since they often compare a Western high-fat, low-diversity diet against a low-fat but higher-diversity chow.[42] The health benefits after bariatric surgery may also involve changes in the gut microbiota by increasing gut permeability.[42]
* Mallory-Denk body
* Ballooning degeneration
* NASH (inflammation) and fibrosis stage 1
* NASH (inflammation) and fibrosis stage 2
* Lobular inflammation
## Diagnosis[edit]
Stages of progression of non-alcoholic fatty liver disease
NAFLD is defined by evidence of fatty liver without another factor that could explain the liver fat accumulation, such as excessive alcohol use (>21 standard drinks/week for men and >14 for women in the USA; >30 g daily for men and >20 g for women in UK and EU, >140 g/week for men and >70 g/week for women in Asia-Pacific and most NIH clinical studies), drug-induced steatosis, chronic hepatitis C, heredity or by deficiencies in parenteral nutrition such as choline and endocrine conditions. If any of these factors are observed, an investigation into alternative causes of fatty liver unrelated to NAFLD is recommended. A history of chronic alcohol usage is an important consideration.[2][4][5][10][12]
NAFLD comprises two histological categories: NAFL, and the more aggressive form NASH. The presence of at least 5% fatty liver is common to both NAFL and NASH, but the features of substantial lobular inflammation and hepatocyte injuries such as ballooning or Mallory hyaline only occur in NASH. The majority of NAFL cases show minimal or no inflammation.[2][4][5] Pericentral and perisinusoidal fibrosis occur more often in adult-onset NASH, whereas portal fibrosis is more common in children with the disorder. NASH represents a more advanced stage of NAFL and is associated with poor outcomes such as cardiovascular events, cirrhosis, or hepatocellular carcinoma. ICD-11 does not use the term NAFL as it was deemed confusing with the family of disorders NAFLD. The preferred descriptions are instead: NAFLD without NASH or simple steatosis and "NASH". Also, the modifier with or without fibrosis or cirrhosis completes the diagnostic description.[2][5]
### Blood tests[edit]
Elevated liver enzymes are common. According to National Institute for Health and Care Excellence (NICE) guidelines, it is disadvised to test enzymes levels to rule out NAFLD, as they are often within the normal range even in advanced disease.[7][10][18]
Blood tests that are useful to confirm diagnosis or rule out others include erythrocyte sedimentation rate, glucose, albumin, and kidney function. Because the liver is important for making proteins used in blood clotting, coagulation-related studies are often carried out, especially the INR (international normalized ratio). In people with fatty liver with associated inflammatory injury (steatohepatitis) blood tests are usually used to rule out viral hepatitis (hepatitis A, B, C and herpesviruses such as Epstein-Barr virus or cytomegalovirus), rubella, and autoimmune diseases. Low thyroid activity is more prevalent in people with NASH, which would be detected by determining the thyroid-stimulating hormone.[43] Some biomarker-based blood tests have been developed and may be useful for diagnosis.[44]
Although blood tests cannot diagnose NAFLD, circulating serum biomarkers of liver fibrosis can give moderate estimates in the diagnosis of liver fibrosis and cirrhosis. The ratio of the transaminase liver enzyme aspartate aminotransferase (AST) to platelets in the blood, known as the AST/platelet ratio index (APRI score), and Fibrotest are recommended as the preferred noninvasive tests for cirrhosis by the Asian-Pacific Association for Study of the Liver (APASL).[45] Several other scores such as FIB-4 score and NAFLD fibrosis score can also reflect the burden of the fibrosis in the liver,[46] and previous studies have confirmed that these score can predict future development of mortality and liver cancer.[47]
### Imaging[edit]
MRI of a healthy liver (top row) and one with severe steatosis (bottom row)
A liver ultrasound scan or magnetic resonance imaging (MRI) can diagnose steatosis,[48] but not fibrosis and confirmation of early cirrhosis detection by ultrasound by other diagnostic methods is recommended.[45] The European Association for the Study of the Liver (EASL) recommends screening for steatosis whenever NAFLD is suspected as this is a strong predictor of the disease evolution and predicts future type 2 diabetes, cardiovascular events, and hypertension.[12] These non-invasive methods can be used for NAFLD screening but are not accepted as a substitute for liver biopsy in NAFLD nor NASH clinical trials, as only a liver biopsy can define liver pathology.[5][8]
CT scans and MRIs are more accurate in detecting cirrhosis than conventional ultrasound.[45] Transient elastography is recommended for the initial assessment of liver fibrosis and cirrhosis and helps to predict complications and prognosis, but the interpretation of results is carefully weighed in the presence of limiting factors, such as steatosis, high BMI, lower degrees of hepatic fibrosis and narrow spaces between the ribs (intercostal spaces). However, transient elastography can fail for people with pre-hepatic portal hypertension. Transient elastography is not considered to be a replacement for liver biopsy.[45]
Magnetic resonance elastography (MRE) is an emerging method that can accurately assess hepatic fibrosis and is recommended by the APASL.[45] MRE possesses a good sensitivity to quantify hepatic fat and excellent accuracy to detect fibrosis in NAFLD regardless of BMI and inflammation and is suggested as a more reliable alternative to diagnose NAFLD and its progression to NASH compared to ultrasound and blood tests.[21][24][49][50]
### Liver biopsy[edit]
A small quantity of tissue is sampled from the liver when doing a biopsy, which is then examined under a microscope
Micrograph of non-alcoholic fatty liver disease, demonstrating marked steatosis (fat in liver cells appears white; connective tissue, blue). Trichrome stain
A liver biopsy (tissue examination) is the only test widely accepted (gold standard) as definitively diagnosing and distinguishing NAFLD (including NAFL and NASH) from other forms of liver disease and can be used to assess the severity of the inflammation and resultant fibrosis. However, since most people affected by NAFLD are likely to be asymptomatic, liver biopsy presents too high a risk for routine diagnosis, so other methods are preferred, such as liver ultrasonography or liver MRI. For young people, guidelines recommend liver ultrasonography, but biopsy remains the best evidence.[4][5][10][21] Liver biopsy is also the gold standard to detect hepatic fibrosis and assess its progression.[45] Routine liver function blood tests are not sensitive enough to detect NAFLD, and biopsy is the only procedure that can reliably differentiate NAFL from NASH.[12]
There are several liver biopsy techniques available to obtain liver tissue. Percutaneous liver biopsy remains the most common practice. Biopsies can also be performed via the transvenous route, either during surgery or by laparoscopy, especially for people with contraindications to a percutaneous approach. The liver biopsy can also be image-guided, in real-time or not, which is recommended for some clinical situations such as people with known intra-hepatic lesions, previous intra-abdominal surgery who may have adhesions, a small liver that is difficult to percuss, obese people and people with evident ascites. Vital signs must be monitored frequently afterward (at least every 15 minutes in the hour following the biopsy).[45]
According to AASLD guidelines, a liver biopsy may be considered in people with NAFLD who are at increased risk of having steatohepatitis with or without advanced fibrosis, but only when all other competing chronic liver diseases are excluded (such as alcoholic liver disease). The presence of metabolic syndrome, NAFLD Fibrosis Score (FIB-4), or liver stiffness (as measured by Vibration-controlled transient elastography or MRE) can identify the individuals who are at higher risk of steatohepatitis or advanced fibrosis.[4]
The AASLD and ICD-11 consider that clinically useful pathology reporting distinguishes "between NAFL (steatosis), NAFL with inflammation and NASH (steatosis with lobular and portal inflammation and hepatocellular ballooning)" with the presence or absence of fibrosis being described and optionally comment on severity.[4][5] The EASL recommends the Fatty Liver Inhibition of Progression (FLIP) algorithm to grade the ballooning and classify NAFLD-associated liver injury, and the use of the NAFLD Activity Score (NAS) to grade the severity of NASH rather than for its diagnosis. They also consider the steatosis, activity, and fibrosis (SAF) score to be an accurate and reproducible scoring system.[12] The AASLD recommends the use of the NAS scoring system with or without the SAF score if deemed appropriate.[4] The Asia-Pacific Working Group on NAFLD disadvises the use of NAS, as it is considered uninformative for NAFLD and inappropriate to diagnose NASH.[8]
For liver fibrosis assessment, percutaneous liver biopsy, with or without image guidance, is contraindicated in uncooperative people.[45] Transjugular liver biopsy is indicated for any person with diffuse liver disease who needs a biopsy but has a contraindication to percutaneous biopsy or needs a hemodynamic evaluation for diagnostic purposes. A transvenous liver biopsy is recommended instead of a percutaneous approach in people with clinically evident ascites, although percutaneous biopsy is an acceptable alternative approach after the removal of ascites.[45]
## Management[edit]
NAFLD warrants treatment regardless of whether the affected person is overweight or not.[5] NAFLD is a preventable cause of death.[17] Guidelines are available from the American Association for the Study of Liver Diseases (AASLD), American Association of Clinical Endocrinologists (AACE) National Institute for Health and Care Excellence (NICE), the European Association for the Study of the Liver (EASL), and the Asia-Pacific Working Party on NAFLD.[4][5][8][10][12][51][52]
### Lifestyle[edit]
Weight loss is the most effective treatment for NAFLD. A loss of 4% to 10% body weight is recommended, with 10% to 40% weight loss completely reversing NASH without cirrhosis. A structured weight loss program helps people with NAFLD lose more weight compared with advice alone. This type of program also leads to improvements in NAFLD measured using blood tests, ultrasound, imaging, or liver biopsies. Although fibrosis improves with lifestyle interventions and weight loss, there is limited evidence for cirrhosis improvement.[5][8][51][53]
A combination of improved diet and exercise, rather than either alone, appears to best help manage NAFLD and reduce insulin resistance.[4][9][12][54][55] Motivational support, such as with cognitive behavioral therapy, is helpful, as most people with NAFLD do not perceive their condition as a disease, and thus have a low motivation to change.[4][7][10][12][28]
Higher-intensity behavioral weight loss therapies (diet and exercise combined) may produce more weight loss than lower-intensity ones. Weight loss is associated with improvements in biomarkers, NAFLD grade, and reduced chances of NASH, but their impact on long-term health is yet unknown. A 2019 systematic review thus suggests a change of guidelines to recommend these therapies for NAFLD management.[53]
#### Diet[edit]
Treatment of NAFLD typically involves counseling to improve nutrition and calorie restriction.[7][51][56] People with NAFLD can benefit from a moderate to low-carbohydrate diet and a low-fat diet.[7][57] The Mediterranean diet also showed promising results in a 6-week study with a reduction of NASH induced inflammation and fibrosis, independently from weight loss.[7][12][55][58] Tentative evidence supports dietary interventions in individuals with fatty liver who are not overweight.[59]
The EASL recommends energy restriction of 500–1000 kcal per week less than the normal daily diet (a very-low-calorie diet), a target of 7–10% weight loss for obese/overweight NAFLD, a low- to moderate-fat, and moderate- to high-carbohydrate diet, or a low-carbohydrate ketogenic or high-protein diet such as the Mediterranean diet, and avoiding all beverages and food containing fructose.[12]
Alcohol is an aggravating factor, and the AASLD recommends that people with NAFLD or NASH avoid alcohol consumption.[4][7][10][60] The EASL allows alcohol consumption below 30g/day for men and 20g/day for women.[12] The role of coffee consumption for NAFLD treatment is unclear though some studies indicate that regular coffee consumption may have protective effects.[12][61][62]
Vitamin E does not improve established liver fibrosis in those with NAFLD but seems to improve certain markers of liver function and reduces inflammation and fattiness of the liver in some people with NAFLD.[4][7][10] The Asia-Pacific Work Group advises that Vitamin E may improve liver condition and aminotransferase levels, but only in adults without diabetes or cirrhosis who have NASH.[8] The NICE guidelines recommend Vitamin E as an option for children and adults with NAFLD with advanced liver fibrosis, regardless of whether the person has diabetes mellitus.[7][10]
Herbal compounds such as silymarin (a milk thistle seed extract),[63] curcumin, a turmeric extract,[64] and green tea appear to improve NAFLD biomarkers and reduce the grade of NAFLD.[34] Studies suggest an association between microscopic organisms that inhabit the gut (microbiota) and NAFLD. Reviews reported the use of probiotics and synbiotics (combinations of probiotics and prebiotics) were associated with improvement in liver-specific markers of hepatic inflammation, measurements of liver stiffness, and steatosis in persons with NAFLD.[65][66]
#### Physical activity[edit]
Weight loss may improve NAFLD and is recommended particularly for obese or overweight people;[67][68][69] similar physical activities and diets are advisable for overweight people with NAFLD as for other obese and overweight people.[10][55] Although physical activity is less important for weight loss than dietary adaptations (to reduce caloric intake),[28] the NICE advises physical activity to reduce liver fat even if there is no overall bodyweight reduction.[7][10] Weight loss, through exercise or diet, is the most effective way to reduce liver fat and help NASH and fibrosis remission.[28] Exercise alone can prevent or reduce hepatic steatosis, but it remains unknown whether it can improve all other aspects of the liver; hence a combined approach with diet and exercise is advised.[4][9] Aerobic exercise may be more effective than resistance training, although there are contradictory results.[7][70] Vigorous training is preferable to moderate training, as only the high-intensity exercise reduced the chances of NASH developing into steatohepatitis or advanced fibrosis.[7][71] The EASL recommends between 150 and 200 min/week in 3 to 5 sessions of moderate-intensity aerobic physical activity or resistance training. Since both effectively reduce liver fat, a pragmatic approach to the choice of physical activity that accounts for the individual's preferences for what they can maintain in the long-term is preferred. Any engagement in physical activity or increase over previous levels is better than remaining sedentary.[12]
### Medication[edit]
Treatment with medications is primarily aimed at improving liver disease and is generally limited to those with biopsy-proven NASH and fibrosis.[4][10][12]
No medicines specifically for NAFLD or NASH had received approval, as of 2018[update], although anti-diabetic medications may help in liver fat loss. While many treatments appear to improve biochemical markers such as alanine transaminase levels, most do not reverse histological abnormalities or improve outcomes.[4][8][72]
Insulin sensitizers (metformin and thiazolidinediones, such as pioglitazone) and liraglutide are not specifically recommended for NAFLD as they do not directly improve the liver condition. They can be indicated for diabetic individuals, after a careful assessment of risks, to reduce insulin resistance and risks of complications.[4][8] Indeed, the side effects associated with thiazolidinedione medications, which include osteopenia, increased fracture risk, fluid retention, congestive heart failure, bladder cancer, and long-term weight gain, have limited their adoption.[7][73][74] Due to these side effects, the AASLD recommends the use of pioglitazone only for individuals with biopsy-proven NASH, and the Asia-Pacific Work Group recommends them only for individuals with NAFLD with known diabetic issues. However, the AASLD advises against the use of metformin as studies were inconclusive about the improvement of the liver's histological condition. Although there was an improvement in insulin resistance and serum aminotransferases, this did not translate into NASH improvements.[4] The NICE provides similar guidelines to the AASLD regarding pioglitazone and recommends it be administered in secondary care to adults with advanced liver fibrosis irrespective of whether or not they have diabetes.[10]
Statin medications appear to improve liver histology and markers of liver biochemistry in people with NAFLD. Since people with NAFLD are at a higher risk of cardiovascular disease, statin treatment is indicated. People with NAFLD are not at higher risk for serious liver injury from statins, according to AASLD and EASL. However, even if statins are safe to use in people with NASH cirrhosis, the AASLD suggests avoiding them in people with decompensated cirrhosis.[4][12][75] Guidelines recommend statins to treat dyslipidemia for people with NAFLD. According to NICE guidelines, statins can continue unless liver enzyme levels double within three months of starting statins.[10] Treatment with pentoxifylline is not recommended.[8]
As of 2018, neither the AASLD nor the Asia-Pacific Working Group recommends obeticholic acid or elafibranor due to inconsistent results for NASH treatment and concerns about safety.[4][8]
Omega-3 fatty acids may reduce liver fat and improve blood lipid profile but do not seem to improve liver histology (fibrosis, cirrhosis, cancer).[8] The NICE does not recommend omega-3 fatty acid supplementation since randomized trials were inconclusive.[7][10] Previous systematic reviews found that omega-3 fatty acid supplementation in those with NAFLD/NASH using doses of one gram daily or more (median dose four grams/day with median treatment duration six months) has been associated with improvements in liver fat.[28][76] According to AASLD guidelines, "omega-3 fatty acids should not be used as a specific treatment of NAFLD or NASH, but they may be considered to treat hypertriglyceridemia for patients with NAFLD".[4]
### Surgery[edit]
For severely obese individuals with NAFLD or NASH, bariatric surgery improves or cures the liver disease if there is no cirrhosis nor liver cancer.
Bariatric surgery is an effective method for obese and diabetic individuals with NAFLD to induce weight loss and reduce or resolve NASH inflammation, including fibrosis, and improve longevity.[7][8][12][28][77][78] For the AASLD, bariatric surgery can be considered only for NASH on a case-by-case basis by an experienced bariatric surgery program.[4] Indeed, some individuals might develop new or worsened features of NAFLD.[78]
About 92% of people with NAFLD saw an improvement in steatosis and 70% a complete resolution after bariatric surgery.[79]
A preoperative diet such as a low-calorie diet or a very-low-calorie diet is usually recommended to reduce liver volume by 16–20%. Preoperative weight loss is the only factor associated with postoperative weight loss.[80][81] Preoperative weight loss can reduce operative time and hospital stay,[80][82][83] although there is insufficient evidence whether preoperative weight loss reduces long-term morbidity or complications.[83][84] Weight loss and decreases in liver size may be independent of the amount of calorie restriction.[81]
The APWG on NAFLD recommends bariatric surgery as a treatment option for those with class II obesity (BMI >32.5 kg/m² for Asians, 35 kg/m² for Caucasians). They consider its effects on improving liver-related complications as unproven yet, but it effectively increases longevity by improving cardiovascular factors.[8]
Surgery carries more risks for individuals with NASH cirrhosis, with a review estimating overall morbidity to be 21%. For people with NAFLD who have undifferentiated cirrhosis, the APWG recommends an investigation to determine the cause of the cirrhosis as well as the person's liver function and whether they have portal hypertension.[8]
### Screening[edit]
Cardiovascular system screening is considered mandatory by the EASL, as NAFLD outcomes often result in cardiovascular complications,[12] which can manifest as subclinical atherosclerosis, the cause of the majority of NAFLD-related deaths.[32][85] People with NAFLD are at high risk for cardiovascular morbidity and mortality, and "aggressive modification of cardiovascular disease risk factors is warranted in all patients with NAFLD," according to AASLD.[4]
The AASLD further recommends for people with a cirrhotic NASH to be systematically screened for gastric and esophageal varices and liver cancer. They do not recommend routine liver biopsies and screening for liver cancer for non-cirrhotic people with NASH, but such screening sometimes occurs on a case-by-case basis.[4]
Also, people with NAFLD may be considered for screening for hepatocellular carcinoma (liver cancer) and gastroesophageal varices. The NICE advises regular screening of NAFLD for advanced liver fibrosis every three years to adults and every two years for children using the enhanced liver fibrosis (ELF) blood test.[10] Follow-up is recommended for people with obesity and insulin resistance using the homeostasis model assessment of insulin resistance (HOMA-IR). People with NASH with fibrosis and hypertension merit closer monitoring as there is a higher risk of disease progression.[12]
### Transplantation[edit]
NAFLD is the second most common indication for liver transplantation in the US and Europe as of 2017.[8] NAFLD/NASH is expected to become the leading cause of liver transplantation by 2020.[86]
For people with NASH and end-stage liver disease, liver failure, or liver cancer, liver transplantation is an accepted procedure according to the EASL.[12] People with NASH cirrhosis NASH who are being considered for a liver transplant warrant systematic evaluation for cardiovascular diseases (whether the symptoms are apparent or not).[4]
The overall survival is comparable to transplantation following other diseases.[8][12] People with NASH cirrhosis who undergo liver transplantation are more likely to die post-transplant because of cardiovascular disease or chronic kidney disease. These people with NASH are often older and are thus more prone to these complications.[8] For these reasons and others, individuals with morbid obesity (BMI > 40 kg/m²) and NASH with cirrhosis may be considered unfit for liver transplantation until they follow lifestyle modifications to reduce bodyweight.[8] Diabetic people with poor glycemic control are at similar risks, and optimal glycemic control is essential before attempting transplantation.[8]
The Asia Pacific Working Group guidelines recommend healthcare providers discuss lifestyle modifications before and after transplantation to reduce potential surgery risks and to assist with NAFLD management after the transplant.[8]
Simultaneous bariatric surgery and liver transplantation were performed in exceptional circumstances.[8]
After transplantation, liver biopsy is the best method to monitor the evolution of post-transplant fibrosis, with significant fibrosis or portal hypertension one year after transplantation predicting rapid progression and graft loss and indicating the need for urgent intervention.[45]
### Related complications[edit]
There is no special treatment for liver cancer associated with NAFLD/NASH and are treated according to general guidelines on liver cancers.[8]
## Prognosis[edit]
The average progression rate from one stage of liver fibrosis to the next in humans with NASH is estimated to be seven years, compared to 14 years with NAFLD. The course of progression varies with different clinical manifestations among individuals.[18][20][87] Fibrosis in humans with NASH progressed more rapidly than in humans with NAFLD.[7] Obesity predicts a worse long-term outcome than for lean individuals.[88][89] In the Asia-Pacific region, about 25% of NAFLD cases progress to NASH under three years, but only a low proportion (3.7%) develop advanced liver fibrosis.[5] An international study showed that people with NAFLD had a 10‐year survival rate of 81.5%.[4]
NAFLD is a risk factor for fibrosis, hypertension, chronic kidney disease, atrial fibrillation, myocardial infarction, ischemic stroke, and death from cardiovascular causes based on very-low to low-quality evidence from observational studies.[10][90] Although NAFLD can cause cirrhosis and liver failure and liver cancer, most deaths among people with NAFLD are attributable to cardiovascular disease.[32] According to a meta-analysis of 34,000 people with NAFLD over seven years, these individuals have a 65% increased risk of developing fatal or nonfatal cardiovascular events when compared to those without NAFLD.[20]
NAFLD and NASH increase the risk of liver cancer. Cirrhosis and liver cancer induced by NAFLD were the second cause of liver transplantation in the US in 2017. Liver cancer develops in NASH in the absence of cirrhosis in 45% in the cases,[91] and people with NASH cirrhosis have an increased risk of liver cancer. The rate of liver cancer associated with NASH increased fourfold between 2002 and 2012 in the US, which is more than any other cause of liver cancer. NAFLD constitutes the third most common risk factor for liver cancer.[92] NAFLD and NASH were found to worsen with cirrhosis in respectively 2–3% and 15–20% of the people over a 10–20 year period.[7] Cirrhosis is found in only about 50% of people with NAFLD and with liver cancer, so that liver cancer and cirrhosis are not always linked.[8]
NAFLD may be a precursor of metabolic syndrome, although a bidirectional influence is possible.[93][94][95] The presence and stage of fibrosis are the strongest prognostic factors for liver-related events and mortality, in particular for NAFLD.[18]
## Epidemiology[edit]
Non-alcoholic fatty liver disease prevalence in 2019
NAFLD incidence is rapidly rising, along with obesity and diabetes, and has become the most common cause of liver disease in developed countries, for adults, teenagers, and children.[17][18] The percentage of people with NAFLD ranges from 9 to 36.9% in different parts of the world.[96][97] Approximately 20% of the United States and 25% of the Asia-Pacific populations have non-alcoholic fatty liver.[5][15] Similar prevalence can be found in Europe, although less data is available.[18] NAFLD is the most common in the Middle East (32%) and South America (30%), while Africa has the lowest rates (13%).[4][18] Compared to the 2000s, NAFL and NASH respectively increased 2-fold and 2.5-fold in the 2010s in the USA.[98]
NAFLD and NASH are more prevalent in Hispanics - which can be attributed to high rates of obesity and type 2 diabetes in Hispanic populations, intermediate in Whites, and lowest in Blacks.[16][18][99] NAFLD was observed to be twice as prevalent in men as women.[4] For severely obese individuals, the prevalence of NAFLD rises over 90%, and for those with diabetes, over 60%, and up to 20% for normal-weight people.[18][19] NAFLD is present in 65% to 90% of people that had bariatric surgery, and up to 75% of them have NASH.[8] Ultrasonography and proton NMR spectroscopy studies suggest about 25% of the population seems to be affected by NAFLD or NASH.[5][18]
Although the disease is commonly associated with obesity, a significant proportion of sufferers are normal weight or lean. Lean NAFLD affects between 10–20% of Americans and Europeans, and approximately 25% of the Asians, although some countries have a higher incidence (e.g., India has a very high proportion of lean NAFLD and almost no obese NAFLD). PNPLA3 may be relevant for the progression of NAFLD in lean people. Thus, people suffering from NAFLD deserve consideration for treatment regardless of the presence or absence of obesity.[5][18][28][88]
In children ages 1 to 19, the prevalence was found to be approximately 8% in the general population up to 34% in studies with data from child obesity clinics.[100]
The majority of cryptogenic cirrhosis is believed to be due to NASH.[5] NAFLD prevalence is expected to increase steadily,[101] from 25% in 2018 to a projected 33.5% of people with NAFLD globally in 2030, and from 20% to a projected 27% of those with NAFLD will progress to NASH.[102]
## History[edit]
The first acknowledged case of obesity-related non-alcoholic fatty liver was observed in 1952 by Samuel Zelman.[103][104] Zelman started investigating after observing a fatty liver in a hospital employee who drank more than twenty bottles of Coca-Cola a day. He then went on to design a trial for a year and a half on 20 obese people who were not alcoholic, finding that about half of them had substantially fatty livers.[103] Fatty liver was, however, linked to diabetes since at least 1784[105] — an observation picked up again in the 1930s.[106] Studies in experimental animals implicated choline inadequacy in the 1920s in the 1920s and excess sugar consumption in 1949.[107]
The name "non-alcoholic steatohepatitis" (NASH) was later defined in 1980 by Jurgen Ludwig and his colleagues from the Mayo Clinic[108] to raise awareness of the existence of this pathology, as similar reports previously were dismissed as "patients' lies".[104] This paper was mostly ignored at the time but eventually came to be seen as a landmark paper, and starting in the mid-1990s, the condition began to be intensively studied, with a series of international meetings being held on the topic since 1998.[109] The broader NAFLD term started to be used around 2002.[109][110] Diagnostic criteria began to be worked out, and in 2005 the Pathology Committee of the NIH NASH Clinical Research Network proposed the NAS scoring system.[109]
## Society and culture[edit]
### Political recommendations[edit]
EASL recommends Europe's public health authorities to "restrict advertising and marketing of sugar-sweetened beverages and industrially processed foods high in saturated fat, sugar, and salt", as well as "fiscal measures to discourage the consumption of sugar-sweetened beverages and legislation to ensure that the food industry improves labeling and the composition of processed foods", as well as "public awareness campaigns on liver disease, highlighting that it is not only linked to excessive consumption of alcohol".[101]
### Lobbying[edit]
In France, the French syndicate of non-alcoholic beverages "Boissons Rafraîchissantes de France" (that included soft drink producers such as Coca-Cola France, Orangina, PepsiCo France) was denounced by the French journal fr:Canard Enchainé for misleading consumers using a communication on their website titled "Better understanding the NASH pathology",[111] explaining that "NASH pathology is sometimes called the soda illness by language abuse or an unfortunate semantic shortcut, as it is not directly linked to the consumption of non-alcoholic beverages". This page and others on the same website, such as one titled "Say no to disinformation," were since then removed.[112]
## Children[edit]
Pediatric NAFLD was first reported in 1983.[113][114] It is the most common chronic liver disease among children and adolescents since at least 2007, affecting 10 to 20% of them in the US in 2016.[18][114][115] NAFLD is associated with metabolic syndrome, which is a cluster of risk factors that contribute to the development of cardiovascular disease and type 2 diabetes mellitus. Studies have demonstrated that abdominal obesity and insulin resistance, in particular, are significant contributors to the development of NAFLD.[116][117][118][119][120] Coexisting liver diseases, such as hepatitis C and cardiovascular diseases such as atherosclerosis, are also associated with an increased risk of NAFLD.[21][32] Some children were diagnosed as early as two years old, with a mean age of diagnosis between 11–13 years old.[114] The mean age is usually above 10 years, as children can also report non-specific symptoms and are thus difficult to diagnose for NAFLD.[114]
Boys are more likely to be diagnosed with NAFLD than girls.[21][100] Overweight, or even weight gain, in childhood and adolescence, is associated with an increased risk of NAFLD later in life, with adult NAFLD predicted in a 31-year follow-up study by risk factors during childhood including BMI, plasma insulin levels, male sex, genetic background (PNPLA3 and TM6SF2 variants) and low birth weight, an emerging risk factor for adulthood NAFLD.[18][21] In a study, simple steatosis was present in up to 45% in children with a clinical suspicion of NAFLD.[21] Children with simple steatosis have a worse prognosis than adults, with significantly more of them progressing from NAFLD to NASH compared to adults. Indeed, 17-25% of children with NAFLD develop a NASH in general, and up to 83% for children with severe obesity (versus 29% for adults), further suggesting that hepatic fibrosis seems to follow a more aggressive clinical course in children compared to adults.[114]
Early diagnosis of NAFLD in children may help prevent the development of liver disease during adulthood.[118][121] This is challenging as most children with NAFLD are asymptomatic, with only 42-59% showing abdominal pain.[21][121] Other symptoms might be present, such as right upper quadrant pain or acanthosis nigricans, the latter of which is often present in children with NASH. An enlarged liver occurs in 30–40% of children with NAFLD.[21]
The AASLD recommends a diagnostic liver biopsy in children when the diagnosis is unclear or before starting a potentially hepatotoxic medical therapy.[4] The EASL suggests using fibrosis tests such as elastography, acoustic radiation force impulse imaging, and serum biomarkers to reduce the number of biopsies.[12] In follow up, NICE guidelines recommend that healthcare providers offer children regular NAFLD screening for advanced liver fibrosis every two years using the enhanced liver fibrosis (ELF) blood test.[10] Several studies also suggest magnetic resonance elastography as an alternative to the less reliable ultrasonography.[21]
Intensive lifestyle modifications, including physical activity and dietary changes, are the first line of treatment according to AASLD and EASL as it improves the liver histology and aminotransferase levels. In terms of pharmacological treatment, the AASLD and EASL do not recommend metformin, but vitamin E may improve liver health for some children.[4][12] The NICE advises the use of vitamin E for children with advanced liver fibrosis, whether they have diabetes or not.[10] The only treatment shown to be effective in childhood NAFLD is weight loss.[122]
Some evidence indicates that maternal undernutrition or overnutrition increases a child's susceptibility to NASH and hastens its progression.[123]
## Research[edit]
### Diagnosis and biomarkers[edit]
Since a NAFLD diagnosis based on a liver biopsy is invasive and makes it difficult to estimate epidemiology, it is a high research priority to find accurate, inexpensive, and noninvasive methods of diagnosing and monitoring NAFLD disease and its progression.[24][124] The search for these biomarkers of NAFLD, NAFL, and NASH involves lipidomics, medical imaging, proteomics, blood tests, and scoring systems.[24]
According to a review, proton density fat fraction estimation by magnetic resonance imaging (MRI-PDFF) may be considered the most accurate and even gold standard test to quantify hepatic steatosis. They recommend ultrasound-based transient elastography to accurately diagnose both fibrosis and cirrhosis in a routine clinical setting, with more objectivity than ultrasonography but with lower accuracy than magnetic resonance elastography; and plasma cytokeratin 18 (CK18) fragment levels to be a moderately accurate biomarker of steatohepatitis.[24] However, transient elastography can fail for people with pre-hepatic portal hypertension.[45]
### Medication development[edit]
Medication development for NASH is very active and advancing rapidly. New medications are being designed to target various intrahepatic sites, from regulating lipids and glucose homeostasis to oxidant stress and mitochondrial targets in hepatocytes, inflammatory signals on hepatocytes, and intracellular targets related to hepatic stellate cell activation and fibrogenesis.[20] As of 2018[update], clinical trials are underway for cenicriviroc, elafibranor, obeticholic acid, and selonsertib in phase 3, and several others in phase 2.[4][7][20][125] Since NAFLD is a complex disease that involves several organs and tissues, combination therapies (combining compounds) and conjugate therapies (combining drugs and non-pharmacological therapies such as behavioral therapies or lifestyle changes) are investigated as a way to increase the efficiency of medical treatment.[20][34] However, most trials were relatively short, from three to 18 months, whereas real-world use will involve administration in the long-term.[20]
## See also[edit]
* Foie gras, fatty liver induced in poultry, with pathophysiology homologous to that of NAFLD in humans
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124. ^ Araújo AR, Rosso N, Bedogni G, Tiribelli C, Bellentani S (February 2018). "Global epidemiology of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: What we need in the future". Liver International. 38 Suppl 1: 47–51. doi:10.1111/liv.13643. PMID 29427488.
125. ^ Liyanagedera S, Williams RP, Veraldi S, Nobili V, Mann JP (November 2017). "The pharmacological management of NAFLD in children and adolescents". Expert Review of Clinical Pharmacology. 10 (11): 1225–1237. doi:10.1080/17512433.2017.1365599. PMID 28803504. S2CID 41440566.
## External links[edit]
* NIH page on non-alcoholic steatohepatitis
* Mayo Clinic page on NAFLD
* v
* t
* e
Diseases of the digestive system
Upper GI tract
Esophagus
* Esophagitis
* Candidal
* Eosinophilic
* Herpetiform
* Rupture
* Boerhaave syndrome
* Mallory–Weiss syndrome
* UES
* Zenker's diverticulum
* LES
* Barrett's esophagus
* Esophageal motility disorder
* Nutcracker esophagus
* Achalasia
* Diffuse esophageal spasm
* Gastroesophageal reflux disease (GERD)
* Laryngopharyngeal reflux (LPR)
* Esophageal stricture
* Megaesophagus
* Esophageal intramural pseudodiverticulosis
Stomach
* Gastritis
* Atrophic
* Ménétrier's disease
* Gastroenteritis
* Peptic (gastric) ulcer
* Cushing ulcer
* Dieulafoy's lesion
* Dyspepsia
* Pyloric stenosis
* Achlorhydria
* Gastroparesis
* Gastroptosis
* Portal hypertensive gastropathy
* Gastric antral vascular ectasia
* Gastric dumping syndrome
* Gastric volvulus
* Buried bumper syndrome
* Gastrinoma
* Zollinger–Ellison syndrome
Lower GI tract
Enteropathy
Small intestine
(Duodenum/Jejunum/Ileum)
* Enteritis
* Duodenitis
* Jejunitis
* Ileitis
* Peptic (duodenal) ulcer
* Curling's ulcer
* Malabsorption: Coeliac
* Tropical sprue
* Blind loop syndrome
* Small bowel bacterial overgrowth syndrome
* Whipple's
* Short bowel syndrome
* Steatorrhea
* Milroy disease
* Bile acid malabsorption
Large intestine
(Appendix/Colon)
* Appendicitis
* Colitis
* Pseudomembranous
* Ulcerative
* Ischemic
* Microscopic
* Collagenous
* Lymphocytic
* Functional colonic disease
* IBS
* Intestinal pseudoobstruction / Ogilvie syndrome
* Megacolon / Toxic megacolon
* Diverticulitis/Diverticulosis/SCAD
Large and/or small
* Enterocolitis
* Necrotizing
* Gastroenterocolitis
* IBD
* Crohn's disease
* Vascular: Abdominal angina
* Mesenteric ischemia
* Angiodysplasia
* Bowel obstruction: Ileus
* Intussusception
* Volvulus
* Fecal impaction
* Constipation
* Diarrhea
* Infectious
* Intestinal adhesions
Rectum
* Proctitis
* Radiation proctitis
* Proctalgia fugax
* Rectal prolapse
* Anismus
Anal canal
* Anal fissure/Anal fistula
* Anal abscess
* Hemorrhoid
* Anal dysplasia
* Pruritus ani
GI bleeding
* Blood in stool
* Upper
* Hematemesis
* Melena
* Lower
* Hematochezia
Accessory
Liver
* Hepatitis
* Viral hepatitis
* Autoimmune hepatitis
* Alcoholic hepatitis
* Cirrhosis
* PBC
* Fatty liver
* NASH
* Vascular
* Budd–Chiari syndrome
* Hepatic veno-occlusive disease
* Portal hypertension
* Nutmeg liver
* Alcoholic liver disease
* Liver failure
* Hepatic encephalopathy
* Acute liver failure
* Liver abscess
* Pyogenic
* Amoebic
* Hepatorenal syndrome
* Peliosis hepatis
* Metabolic disorders
* Wilson's disease
* Hemochromatosis
Gallbladder
* Cholecystitis
* Gallstone / Cholelithiasis
* Cholesterolosis
* Adenomyomatosis
* Postcholecystectomy syndrome
* Porcelain gallbladder
Bile duct/
Other biliary tree
* Cholangitis
* Primary sclerosing cholangitis
* Secondary sclerosing cholangitis
* Ascending
* Cholestasis/Mirizzi's syndrome
* Biliary fistula
* Haemobilia
* Common bile duct
* Choledocholithiasis
* Biliary dyskinesia
* Sphincter of Oddi dysfunction
Pancreatic
* Pancreatitis
* Acute
* Chronic
* Hereditary
* Pancreatic abscess
* Pancreatic pseudocyst
* Exocrine pancreatic insufficiency
* Pancreatic fistula
Other
Hernia
* Diaphragmatic
* Congenital
* Hiatus
* Inguinal
* Indirect
* Direct
* Umbilical
* Femoral
* Obturator
* Spigelian
* Lumbar
* Petit's
* Grynfeltt-Lesshaft
* Undefined location
* Incisional
* Internal hernia
* Richter's
Peritoneal
* Peritonitis
* Spontaneous bacterial peritonitis
* Hemoperitoneum
* Pneumoperitoneum
Classification
D
* ICD-10: K75.8, K76.0
* ICD-10-CM: K75.81, K76.0
* ICD-9-CM: 571.8
* MeSH: D065626
* DiseasesDB: 29786
External resources
* eMedicine: med/775
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Non-alcoholic fatty liver disease
|
c0400966
| 7,390 |
wikipedia
|
https://en.wikipedia.org/wiki/Non-alcoholic_fatty_liver_disease
| 2021-01-18T18:51:41 |
{"gard": ["6430"], "mesh": ["D065626"], "umls": ["C0400966"], "icd-9": ["571.8"], "icd-10": ["K76.0"], "orphanet": ["33271"], "wikidata": ["Q1546498"]}
|
Unilateral polymicrogyria is a cerebral cortical malformation characterized by unilateral excessive cortical folding and abnormal cortical layering. It comprises two sub-types depending on the areas affected: unilateral hemispheric and focal polymicrogyria (see these terms).
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Unilateral polymicrogyria
|
c4024960
| 7,391 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=268943
| 2021-01-23T17:42:14 |
{"icd-10": ["Q04.3"]}
|
Farag and Teebi (1990) described 3 brothers, the offspring of first cousins once removed, with this combination. The father had hypertelorism and a brother of his, who was married to a second cousin, had a daughter with hypertelorism and tetralogy of Fallot. All 4 affected relatives had mild or borderline mental retardation.
INHERITANCE \- Autosomal recessive HEAD & NECK Face \- Long philtrum Ears \- Posteriorly rotated ears \- Low-set ears Eyes \- Hypertelorism \- Epicanthal folds \- Narrow palpebral fissures Nose \- Flat nasal bridge CARDIOVASCULAR Heart \- Tetralogy of Fallot \- Patent foramen ovale \- Absent pulmonary valve Vascular \- Patent ductus arteriosus GENITOURINARY External Genitalia (Male) \- Hypospadias SKELETAL Spine \- Spina bifida occulta Feet \- Talipes equinovarus NEUROLOGIC Central Nervous System \- Mental retardation, mild ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
HYPERTELORISM AND TETRALOGY OF FALLOT
|
c1855903
| 7,392 |
omim
|
https://www.omim.org/entry/239711
| 2019-09-22T16:26:51 |
{"mesh": ["C538386"], "omim": ["239711"]}
|
Castle et al. (1992) described a family in which 2 male first cousins, sons of sisters, had type I hereditary motor and sensory neuropathy as well as aplasia cutis congenita of the scalp with underlying skull defect. Another male related to these 2 as a first cousin once removed through females had died at birth with a gross skull defect. The obligatory carrier females in this family, although not aware of muscle weakness or sensory abnormality, were found to have minor distal muscle wasting with some degree of evident denervation. Sensory testing revealed abnormalities. Type I CMT is characterized by delayed nerve induction. X-linked CMT without scalp defect has been related to at least 3 loci (302800, 302801, and 302802).
Neuro \- Type I hereditary motor and sensory neuropathy Skull \- Skull defect under scalp aplasia Inheritance \- X-linked Misc \- Minor distal muscle wasting and denervation in carrier females Lab \- Delayed nerve induction Skin \- Aplasia cutis congenita of scalp ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
CHARCOT-MARIE-TOOTH PERONEAL MUSCULAR ATROPHY, X-LINKED, WITH APLASIA CUTIS CONGENITA
|
c1844864
| 7,393 |
omim
|
https://www.omim.org/entry/302803
| 2019-09-22T16:18:37 |
{"mesh": ["C538077"], "omim": ["302803"]}
|
Robinson et al. (1977) described 2 second cousins with infantile polymyoclonus. No other familial cases have been described. The main clinical features are chaotic rapid conjugate ocular movements, ataxia, somatic myoclonus, and irritability. The syndrome is not progressive. It runs a protracted course with exacerbations and remissions. It has been called the 'dancing eyes, dancing feet syndrome.'
Misc \- Protracted course with exacerbations and remissions Neuro \- Infantile polymyoclonus \- Chaotic rapid conjugate ocular movements \- Ataxia \- Somatic myoclonus \- Irritability \- Dancing eyes \- Dancing feet Inheritance \- Autosomal recessive ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
POLYMYOCLONUS, INFANTILE
|
c1849731
| 7,394 |
omim
|
https://www.omim.org/entry/263550
| 2019-09-22T16:23:16 |
{"mesh": ["C535524"], "omim": ["263550"]}
|
Prostate cancer is a common disease that affects men, usually in middle age or later. In this disorder, certain cells in the prostate become abnormal and multiply without control or order to form a tumor. The prostate is a gland that surrounds the male urethra and helps produce semen, the fluid that carries sperm.
Early prostate cancer usually does not cause pain, and most affected men exhibit no noticeable symptoms. Men are often diagnosed as the result of health screenings, such as a blood test for a substance called prostate specific antigen (PSA) or a medical procedure called a digital rectal exam. As the tumor grows larger, signs and symptoms can include difficulty starting or stopping the flow of urine, a feeling of not being able to empty the bladder completely, blood in the urine or semen, or pain with ejaculation. However, these changes can also occur with many other genitourinary conditions. Having one or more of these symptoms does not necessarily mean that a man has prostate cancer.
The severity and outcome of prostate cancer varies widely. Early-stage prostate cancer can usually be treated successfully, and some older men have prostate tumors that grow so slowly that they may never cause health problems during their lifetime, even without treatment. In other men, however, the cancer is much more aggressive; in these cases, prostate cancer can be life-threatening.
Some cancerous tumors can invade surrounding tissue and spread to other parts of the body. Tumors that begin at one site and then spread to other areas of the body are called metastatic cancers. The signs and symptoms of metastatic cancer depend on where the disease has spread. If prostate cancer spreads, cancerous cells most often appear in the lymph nodes, bones, lungs, liver, or brain. Bone metastases of prostate cancer most often cause pain in the lower back, pelvis, or hips.
A small percentage of all prostate cancers cluster in families. These hereditary cancers are associated with inherited gene mutations. Hereditary prostate cancers tend to develop earlier in life than non-inherited (sporadic) cases.
## Frequency
About 1 in 7 men will be diagnosed with prostate cancer at some time during their life. In addition, studies indicate that many older men have undiagnosed prostate cancer that is non-aggressive and unlikely to cause symptoms or affect their lifespan. While most men who are diagnosed with prostate cancer do not die from it, this common cancer is still the second leading cause of cancer death among men in the United States.
More than 60 percent of prostate cancers are diagnosed after age 65, and the disorder is rare before age 40. In the United States, African Americans have a higher risk of developing prostate cancer than do men of other ethnic backgrounds, and they also have a higher risk of dying from the disease.
## Causes
Cancers occur when genetic mutations build up in critical genes, specifically those that control cell growth and division or the repair of damaged DNA. These changes allow cells to grow and divide uncontrollably to form a tumor. In most cases of prostate cancer, these genetic changes are acquired during a man's lifetime and are present only in certain cells in the prostate. These changes, which are called somatic mutations, are not inherited. Somatic mutations in many different genes have been found in prostate cancer cells. Less commonly, genetic changes present in essentially all of the body's cells increase the risk of developing prostate cancer. These genetic changes, which are classified as germline mutations, are usually inherited from a parent. In people with germline mutations, changes in other genes, together with environmental and lifestyle factors, also influence whether a person will develop prostate cancer.
Inherited mutations in particular genes, such as BRCA1, BRCA2, and HOXB13, account for some cases of hereditary prostate cancer. Men with mutations in these genes have a high risk of developing prostate cancer and, in some cases, other cancers during their lifetimes. In addition, men with BRCA2 or HOXB13 gene mutations may have a higher risk of developing life-threatening forms of prostate cancer.
The proteins produced from the BRCA1 and BRCA2 genes are involved in fixing damaged DNA, which helps to maintain the stability of a cell's genetic information. For this reason, the BRCA1 and BRCA2 proteins are considered to be tumor suppressors, which means that they help keep cells from growing and dividing too fast or in an uncontrolled way. Mutations in these genes impair the cell's ability to fix damaged DNA, allowing potentially damaging mutations to persist. As these defects accumulate, they can trigger cells to grow and divide uncontrollably and form a tumor.
The HOXB13 gene provides instructions for producing a protein that attaches (binds) to specific regions of DNA and regulates the activity of other genes. On the basis of this role, the protein produced from the HOXB13 gene is called a transcription factor. Like BRCA1 and BRCA2, the HOXB13 protein is thought to act as a tumor suppressor. HOXB13 gene mutations may result in impairment of the protein's tumor suppressor function, resulting in the uncontrolled cell growth and division that can lead to prostate cancer.
Inherited variations in dozens of other genes have been studied as possible risk factors for prostate cancer. Some of these genes provide instructions for making proteins that interact with the proteins produced from the BRCA1, BRCA2, or HOXB13 genes. Others act as tumor suppressors through different pathways. Changes in these genes probably make only a small contribution to overall prostate cancer risk. However, researchers suspect that the combined influence of variations in many of these genes may significantly impact a person's risk of developing this form of cancer.
In many families, the genetic changes associated with hereditary prostate cancer are unknown. Identifying additional genetic risk factors for prostate cancer is an active area of medical research.
In addition to genetic changes, researchers have identified many personal and environmental factors that may contribute to a person's risk of developing prostate cancer. These factors include a high-fat diet that includes an excess of meat and dairy and not enough vegetables, a largely inactive (sedentary) lifestyle, obesity, excessive alcohol use, or exposure to certain toxic chemicals. A history of prostate cancer in closely related family members is also an important risk factor, particularly if the cancer occurred at an early age.
### Learn more about the genes associated with Prostate cancer
* AR
* BRCA1
* BRCA2
* CDH1
* EP300
* EZH2
* FGFR2
* FGFR4
* GNMT
* HNF1B
* HOXB13
* IGF2
* ITGA6
* LRP2
* MED12
* NBN
* PCNT
* PTEN
* SRD5A2
* STAT3
* TGFBR1
* WRN
* WT1
Additional Information from NCBI Gene:
* CD82
* CHEK2
* EHBP1
* ELAC2
* EPHB2
* KLF6
* MAD1L1
* MSMB
* MSR1
* MXI1
* PLXNB1
* RNASEL
* ZFHX3
## Inheritance Pattern
Many cases of prostate cancer are not related to inherited gene changes. These cancers are associated with somatic mutations that occur only in certain cells in the prostate.
When prostate cancer is related to inherited gene changes, the way that cancer risk is inherited depends on the gene involved. For example, mutations in the BRCA1, BRCA2, and HOXB13 genes are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase a person's chance of developing cancer. In other cases, the inheritance of prostate cancer risk is unclear. It is important to note that people inherit an increased risk of cancer, not the disease itself. Not all people who inherit mutations in these genes will develop cancer.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Prostate cancer
|
c0376358
| 7,395 |
medlineplus
|
https://medlineplus.gov/genetics/condition/prostate-cancer/
| 2021-01-27T08:25:22 |
{"gard": ["4520"], "mesh": ["D011471"], "omim": ["176807", "607592", "604845", "601518", "611100", "611955", "611868", "611928", "611958", "611959", "614731", "608656", "608658", "609299", "609558", "610321", "602759", "610997", "300147", "300704", "615452", "609717", "603688", "605097"], "synonyms": []}
|
A number sign (#) is used with this entry because HMG-CoA lyase deficiency is caused by homozygous or compound heterozygous mutation in the HMGCL gene (613898) on chromosome 1p.
Description
3-Hydroxy-3-methylglutaryl-CoA lyase deficiency is a rare autosomal recessive disorder with the cardinal manifestations of metabolic acidosis without ketonuria, hypoglycemia, and a characteristic pattern of elevated urinary organic acid metabolites, including 3-hydroxy-3-methylglutaric, 3-methylglutaric, and 3-hydroxyisovaleric acids. Urinary levels of 3-methylcrotonylglycine may be increased. Dicarboxylic aciduria, hepatomegaly, and hyperammonemia may also be observed. Presenting clinical signs include irritability, lethargy, coma, and vomiting (summary by Gibson et al., 1988).
Clinical Features
Faull et al. (1976) reported a 7-month-old male infant from Australia with metabolic acidosis and hypoglycemia, who excreted organic acids suggestive of a defect in 3-hydroxy-3-methylglutaryl CoA lyase, the enzyme that catalyzes the final step of leucine degradation and plays a key role in ketone body formation. The profile of urinary organic acids was different from that of 3 previously identified defects of leucine degradation--maple syrup urine disease (248600), isovaleric acidemia (243500), and methylcrotonylglycinemia (210200). Wysocki and Hahnel (1976) demonstrated marked deficiency of 3-hydroxy-3-methylglutaryl coenzyme A lyase activity in leukocytes from the infant reported by Faull et al. (1976). Both parents had reduced levels of HMG-CoA lyase in leukocytes. The biochemical diagnosis is made by the finding of abnormal organic aciduria with greatly increased urinary excretion of 3-hydroxy-3-methylglutaric acid and related substances. The enzyme can be measured in leukocytes and fibroblasts. Shilkin et al. (1981) provided further follow-up on this patient. At the age of 4 years and 7 months, he appeared to be well and developing satisfactorily. His diet had been difficult to control and the biochemical defect was exceedingly sensitive to small amounts of leucine in the diet.
Duran et al. (1979) observed a Moroccan family with 4 of 7 sibs affected. Prenatal diagnosis was possible by demonstration of HMG acid in the mother's urine. Recessive inheritance was supported by intermediate levels of lyase activity in both parents.
Leonard et al. (1979) reported a patient with HGM-CoA lyase deficiency presenting as Reye syndrome.
Robinson et al. (1980) described the case of a 2-year-old boy with acute fever, malaise, and somnolence with hepatomegaly, hyperammonemia, high SGOT, hypoglycemia and mild acidosis. Liver biopsy showed diffuse accumulation of lipid droplets in swollen hepatocytes. Abnormal urinary metabolites included beta-hydroxy-beta-methyl-glutarate (HMG). In liver and cultured skin fibroblasts, HMG-CoA lyase activity was about 10% of normal. The urine had an odor resembling that of a cat. The child's parents were unrelated and came from San Miguel in the Azores. Robinson et al. (1980) noted features resembling Reye syndrome.
Wilson et al. (1984) stated that acute pancreatitis is found at autopsy in over 7% of cases of Reye syndrome. They reported a 5-year-old child with a history of recurrent hypoglycemia who presented with a Reye-like syndrome and acute pancreatitis. HMG-CoA lyase deficiency was established by enzymatic analysis of skin fibroblasts and lymphocytes. This disorder is one of an increasing list of inborn errors of metabolism that clinically present as Reye syndrome or nonketotic hypoglycemia.
Berry et al. (1981) found deficiency of 3-hydroxy-3-methylglutarate CoA lyase in liver and cultured fibroblasts of 2 related children ascertained because of abnormal metabolites in the urine: 3-hydroxy-3-methylglutaric acid, 3-methylglutaconic acid, 3-methylglutaric acid, and 3-hydroxyisovaleric acid. A shortage of glucose-sparing ketone bodies normally produced during fasting was thought to be responsible for the hypoglycemia that characterizes this metabolic defect. The absence of ketonuria in this disorder is a direct consequence of the metabolic lesion. HMG-CoA lyase is involved in ketogenesis, and the patient with the deficiency is compromised in the ability to generate ketone bodies.
Despite the clinical heterogeneity observed with HMG-CoA lyase deficiency, Sovik et al. (1984) could find no evidence of biochemical heterogeneity (residual enzyme activity in cultured fibroblasts was equally low in all 7 cases studied) or genetic heterogeneity (no complementation was observed in heterokaryons).
Roe et al. (1986) demonstrated 3-methylglutarylcarnitine in the urine of 4 patients with this disorder and suggested this as the cause of an apparently secondary carnitine deficiency. They suggested that dietary supplementation with carnitine may be warranted.
Wysocki and Hahnel (1986) reviewed 12 patients, and Gibson et al. (1988) reported 5 others. Gibson et al. (1988) reviewed 18 reported cases.
Ribes et al. (1990) described sudden death in a 13-month-old boy with HMG-CoA lyase deficiency.
Barash et al. (1990) determined HMG-CoA lyase activity by the spectrophotometric method of Wanders et al. (1988) in polymorphonuclear leukocytes and lymphocytes obtained from 33 persons in 4 generations of a highly consanguineous Arab-Bedouin family. Seven subjects were obligatory heterozygotes, being parents and grandparents of 3 propositi; in 7 additional subjects, enzyme activities in both cell types were in the heterozygous range. No asymptomatic homozygotes were found.
Grunert et al. (2017) reviewed the clinical presentation and outcome in a series of 37 patients with HMGCLD, including 30 from Turkey and the rest from Belgium, Germany, The Netherlands, and Switzerland. Most patients (94%) presented with an acute metabolic decompensation in the first year of life, approximately half in the neonatal period. The most common clinical symptoms were recurrent vomiting, seizures, and impaired vigilance. The most common laboratory findings were hypoglycemia, acidosis, an increased anion gap, hyperammonemia, and elevated transaminase activities. Of 32 patients, 10 had no further metabolic decompensations after diagnosis, and 22 had at least one more metabolic crisis, most often associated with infections, especially gastroenteritis or respiratory tract infections. Half of the patients had normal cognitive development, and the remainder had psychomotor deficits of variable severity. Six of the patients had died at a mean age of 11 years (range, 4 months to 40 years).
Clinical Management
HMG-CoA lyase deficiency is treatable by diet and avoidance of prolonged fasting. Leucine is restricted and supplementary glucose given to prevent hypoglycemia. Without treatment, death occurs early (Duran et al., 1979; Gibson et al., 1988).
Inheritance
HMG-CoA lyase deficiency is an autosomal recessive disorder (Mitchell et al., 1992).
Population Genetics
Muroi et al. (2000) stated that the incidence of HMG-CoA lyase deficiency is low, except in Saudi Arabia where the deficiency comprises 16% of all organic acidemia (Ozand et al., 1992). Otherwise, only 41 cases had been reported in the English literature and only 5 cases had been reported from Japan. Ozand et al. (1992) reported that the disorder in Saudi Arabian patients is particularly severe.
Molecular Genetics
Mitchell et al. (1993) characterized mutation in the HMGCL gene causing human HL deficiency; see 613898.0001-613898.0002.
By genomic Southern blot analysis and exonic PCR, Wang et al. (1996) found that 2 of 33 HMGCL-deficient patient probands were homozygous for different large deletions in the gene (see, e.g., 613898.0003).
Muroi et al. (2000) presented the results of a molecular analysis of all known 5 Japanese cases of HMG-CoA lyase deficiency together with their clinical phenotypes. Five different mutations were identified: 1 large deletion, 1 nonsense mutation, 1 missense mutation, and 2 splice mutations. A glu279-to-lys (613898.0005) mutation was found in homozygous state in 1 patient and in heterozygous state in a second; all of the other mutations were unique to each family.
Animal Model
By gene targeting, Wang et al. (1998) created a strain of HL-deficient mice. Heterozygous HL-deficient mice were clinically normal, and fibroblasts from homozygous HL-deficient embryos grew normally despite absence of HL activity. In contrast, homozygous HL-deficient embryos died at approximately 11.5 days postcoitum. Histologically, HL-deficient embryos showed marked vacuolization, particularly in the liver. Ultrastructural studies of hepatocytes obtained before death from HL-deficient embryos showed abnormal dilated mitochondria. HL-deficient mice are the first mammalian example of a disease primarily affecting CoA ester metabolism with abnormal prenatal development.
INHERITANCE \- Autosomal recessive HEAD & NECK Head \- Microcephaly (in some patients) RESPIRATORY \- Tachydyspnea \- Kussmal breathing ABDOMEN Liver \- Hepatomegaly Gastrointestinal \- Recurrent vomiting \- Refusal of nutrition SKIN, NAILS, & HAIR Skin \- Paleness MUSCLE, SOFT TISSUES \- Muscular hypotonia NEUROLOGIC Central Nervous System \- Seizures \- Myoclonus \- Spasticity \- Coma (uncommon) \- Abnormal MRI \- White matter abnormalities \- Abnormalities of the basal ganglia \- Abnormal EEG \- Psychomotor retardation, mild to severe (in some patients) Behavioral Psychiatric Manifestations \- Apathy/lethargy \- Somnolence METABOLIC FEATURES \- Metabolic acidosis HEMATOLOGY \- Anemia \- Decreased prothrombin time LABORATORY ABNORMALITIES \- Acidosis \- Hyperammonemia \- Increased anion gap \- Hypoglycemia \- Hyperuricemia \- Elevated transaminase activity \- Elevated lactate level MISCELLANEOUS \- Triggers for acute decompensation include infections, vaccinations, and dietary changes \- Sensitivity to dietary leucine \- Variable features present during metabolic decompensation \- Long-term complications may include mental retardation, seizures, hypotonia, and spasticity MOLECULAR BASIS \- Caused by mutation in the 3-hydroxy-3-methylglutaryl-Coenzyme A lyase gene (HMGCL, 613898.0001 ) ▲ Close
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
3-HYDROXY-3-METHYLGLUTARYL-CoA LYASE DEFICIENCY
|
c1533587
| 7,396 |
omim
|
https://www.omim.org/entry/246450
| 2019-09-22T16:25:56 |
{"omim": ["246450"], "orphanet": ["20"], "synonyms": ["Alternative titles", "HMG-CoA LYASE DEFICIENCY", "HMGCL DEFICIENCY", "HL DEFICIENCY", "HYDROXYMETHYLGLUTARIC ACIDURIA"]}
|
A rare genetic cerebral small vessel disease characterized by recurrent ischemic strokes, often with a predilection for the pons, with typical onset in the fourth or fifth decade of life. Patients present progressive cognitive and motor impairment with pyramidal, bulbar, and cerebellar symptoms, among others. Brain imaging shows multiple lacunar infarcts, typically with involvement of the pons, as well as variable leukoencephalopathy of the cerebral hemispheres.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Pontine autosomal dominant microangiopathy with leukoencephalopathy
|
None
| 7,397 |
orphanet
|
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=477749
| 2021-01-23T18:10:24 |
{"omim": ["618564"], "synonyms": ["PADMAL"]}
|
## Summary
### Clinical characteristics.
ATP8B1 deficiency encompasses a phenotypic spectrum ranging from severe to intermediate to mild, based on an individual's clinical findings and laboratory test results, including liver biopsy.
Severe ATP8B1 deficiency is characterized by onset of symptoms of cholestasis (pruritus and attacks of jaundice) within the first few months of life. Secondary manifestations such as coagulopathy (due to vitamin K deficiency), malabsorption, and poor weight gain may present earlier than age three months. Without surgical intervention, cirrhosis and evolution to end-stage hepatic failure and death usually ensue before the third decade.
Mild ATP8B1 deficiency is characterized by intermittent episodes of cholestasis manifest as severe pruritus and jaundice; chronic liver damage does not typically develop. In contrast to patients in whom bouts of cholestasis are induced only by particular triggers known to increase risk of cholestasis (drug exposure, shifts in hormonal milieu [including those resulting from ingestion of contraceptive drugs or from pregnancy], coexistent malignancy), some or all bouts of cholestasis in individuals with mild ATP8B1 deficiency have different or unknown triggers.
### Diagnosis/testing.
The diagnosis of ATP8B1 deficiency is suspected based on clinical and laboratory findings (often including liver biopsy findings), and confirmed by identification of biallelic ATP8B1 pathogenic variants.
### Management.
Treatment of manifestations: Standard pharmacologic therapies for pruritus associated with cholestasis (e.g., ursodeoxycholic acid, cholestyramine, and/or rifampin) may be temporarily effective but in the long term are relatively ineffective in severe disease. Nutritional therapy and supplementation of fat-soluble vitamins are useful in severe cholestasis. In severe disease, partial external biliary diversion (PEBD) surgery may reduce pruritus. In some individuals it even slows or reverses progression of hepatic fibrosis. Alternative surgical procedures include ileal exclusion, partial internal biliary diversion, and external diversion with a button device. When liver disease fails to respond to this type of surgery or progresses to cirrhosis in patients with severe ATP8B1 deficiency, orthotopic liver transplantation (LTX) is necessary for long-term survival; however, particular complications are relatively common after LTX.
Additional treatment options are available for milder disease, including temporary measures such as nasobiliary drainage and extracorporeal liver support therapy, which may shorten a bout of cholestasis.
### Genetic counseling.
ATP8B1 deficiency is inherited in an autosomal recessive manner. The parents of an affected individual are generally obligate carriers of a pathogenic variant. Intrahepatic cholestasis of pregnancy (ICP) has been reported occasionally in mothers of some individuals with ATP8B1 deficiency. At conception, each sib of a proband has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible if the pathogenic variants in the family are known.
## Diagnosis
ATP8B1 deficiency encompasses a phenotypic spectrum ranging from severe to intermediate to mild, based on an individual's clinical findings and laboratory test results, including liver biopsy.
Severe ATP8B1 deficiency should be considered in children with unremitting cholestasis (typically beginning within the first few months of life) manifest as jaundice, failure to thrive, and/or hemorrhage (due to the coagulopathy of vitamin K deficiency) that has evolved into cirrhosis and end-stage liver disease or that appears likely to evolve to that stage if untreated.
Mild ATP8B1 deficiency should be considered in persons with intermittent manifestations of intrahepatic cholestasis. Although the first episode of cholestasis in infancy may herald disease anywhere along the phenotypic continuum, the older the age at the first episode, the less likely the individual is to develop severe disease.
In mild-to-moderate ATP8B1 deficiency the age at onset of the first episode of cholestasis and the length of episodes and length of disease-free intervals between episodes vary greatly. Episodes of cholestasis typically involve jaundice and pruritus; however, milder episodes may include pruritus only.
"Triggers" for episodes of intrahepatic cholestasis in patients with intermittent cholestasis may include intercurrent illness, ingestion of a drug, or a shift in hormonal milieu (endogenous or exogenous in origin). Paraneoplastic cholestasis must be considered.
Other manifestations (malaise, abdominal discomfort, loose stools) lack specificity.
Extrahepatic manifestations in ATP8B1 deficiency include hearing loss, pancreatitis, pancreatic insufficiency, kidney stones, and resistance to parathyroid hormone [de Pagter et al 1976, Bull et al 1998, Nagasaka et al 2004, Stapelbroek et al 2009, Pawlikowska et al 2010, Folvik et al 2012]. Patients may have diarrhea not solely attributable to fat malabsorption [Davit-Spraul et al 2010, Pawlikowska et al 2010]. Children with severe ATP8B1 deficiency typically manifest failure to thrive and poor growth, beyond that expected in cholestasis alone [Pawlikowska et al 2010]; puberty may also be delayed.
### Testing
#### Laboratory Studies Consistent with ATP8B1 Deficiency
Serum studies consistent with severe ATP8B1 deficiency. See Table 1.
* Low-to-normal serum γ-GT (gamma-glutamyltranspeptidase) activity despite conjugated hyperbilirubinemia and/or severe pruritus
Note: (1) Because γ-GT activity is elevated in most types of cholestasis, forms of cholestasis in which γ-GT is not elevated are called "low-γ-GT cholestasis." (2) Low-to-normal serum γ-GT activity despite conjugated hyperbilirubinemia is also found in disorders of bile acid synthesis and in disorders of bile acid conjugation. See Fast-atom bombardment ionization mass spectrometry (FAB-MS) analysis of urine.
* Serum concentrations of cholesterol are usually not elevated (an unusual finding in cholestasis).
* Serum concentrations of total bile acids are elevated, often markedly so [Davit-Spraul et al 2010, Pawlikowska et al 2010].
Serum studies consistent with mild ATP8B1 deficiency. γ-GT activity is low despite hyperbilirubinemia (see Table 1).
### Table 1.
Clinical Biochemistry Test Results in ATP8B1 Deficiency
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PhenotypeSerum γ-GT ActivitySerum Concentration of CholesterolSerum Concentration of Total Bile AcidsSerum Concentration of Conjugated Bilirubin
SevereLow to normal 1Low to normal 1
(HDL low, oxidized LDL high, triglycerides high) 2Markedly elevatedHigh early w/resolution & subsequent elevation w/end-stage liver disease
MildLow to normal 3Usually low to normal during symptomatic periods 4Markedly elevated during symptomatic periods; normal between episodesNormal between episodes; variable increases during symptomatic periods
1\.
Usually elevated in cholestatic liver disease; see Serum studies consistent with severe ATP8B1 deficiency.
2\.
Nagasaka et al [2005], Nagasaka et al [2009], Pawlikowska et al [2010]
3\.
May be elevated at onset or at resolution of an episode of cholestasis
4\.
Detailed study of one individual with mild ATP8B1 deficiency demonstrated low HDL and other lipid abnormalities during a bout of cholestasis [Nagasaka et al 2007].
Fast-atom bombardment ionization mass spectrometry (FAB-MS) analysis of urine. Normal bile acid species present in elevated concentrations indicate normal bile acid synthesis and conjugation. In ATP8B1 deficiency FAB-MS shows elevated levels of normal bile acid species without unusual bile acid species.
Gas-chromatography / FAB-MS analysis of bile. Depletion of dihydroxy-bile acid species (principally chenodeoxycholic acid) is compatible with ATP8B1 deficiency [Tazawa et al 1985, Emerick et al 2008].
Note: Such analyses of bile and urine should be conducted, if possible, more than two weeks after the last administration of ursodeoxycholic acid (see Management). The presence of this choleretic, an exogenous dihydroxy-bile acid, in bile and urine samples may make interpretation of results more difficult.
Sweat chloride. Concentration of electrolytes in sweat may be elevated.
#### Liver Biopsy
Findings typical of severe ATP8B1 deficiency at presentation are bland intracanalicular cholestasis and scant intrahepatocytic cholestasis.
* At presentation, individuals with ATP8B1 deficiency generally do not have underlying hepatobiliary structural abnormalities; such abnormalities may develop as the disease evolves. Although inflammation, fibrosis, ductular reaction (bile ductular proliferation), and signs of injury to hepatocytes are not features in early stages of severe ATP8B1 deficiency, they develop over months to years [Bull et al 1997]. As the disease progresses, fibrosis of portal tracts develops; centrilobular fibrosis, with perivenular and pericellular accentuation, is generally seen; and bridging fibrosis, both portal-portal and portal-central, supervenes. Neocholangiolar metaplasia in centrilobular regions may make it difficult to distinguish draining venules from portal venules. When cirrhosis evolves, its pattern is micronodular.
* None of the usual signs of injury to hepatocytes in cholestatic disorders of infancy (swelling of hepatocytes, rarefaction of hepatocyte cytoplasm, multinucleation of large hepatocytes ("giant-cell change"), and necrosis of individual hepatocytes) is typical of severe ATP8B1 deficiency. Instead, the usual findings are small, tidy-appearing hepatocytes and varying degrees of rosetting of hepatocytes around variably dilated - even pseudoacinar - lumina of bile canaliculi ("bland intralobular cholestasis," principally intracanalicular rather than hepatocellular). Similar findings are present in mild ATP8B1 deficiency during episodes of cholestasis.
* Although hepatocytes with three or four nuclei may rarely be encountered, cytoplasmic volume per nucleus is not increased: Multinucleate cells are different from "giant cells," an important distinction.
* The bile within canalicular lumina generally appears wispy or pale, unlike the khaki-colored pigment typical in other forms of cholestasis.
* Coarsely granular canalicular bile may be found on transmission electron microscopy (TEM), although treatment with ursodeoxycholic acid may alter this finding. Bile is not ultrastructurally abnormal in mild ATP8B1 deficiency when cholestasis is not present.
* Bile ducts are small and inconspicuous and may appear hypoplastic, with interlobular biliary-tract radicles that are only a cell or two broad in cross-section, a characteristic best ascribed to lack of trophic bile flow. Paucity of interlobular bile ducts, however, is not seen.
Findings in mild ATP8B1 deficiency during an episode of cholestasis resemble those at presentation in severe ATP8B1 deficiency.
Immunohistochemical analysis may be available on a research basis (see Molecular Genetics).
#### Laboratory Studies Diagnostic of ATP8B1 Deficiency
Identification of biallelic ATP8B1 pathogenic variants confirms the diagnosis of ATP8B1 deficiency (see Table 2).
### Table 2.
Summary of Molecular Genetic Testing Used ATP8B1 Deficiency
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Gene 1Test MethodVariants Detected 2Variant Detection Frequency by Test Method 3
ATP8B1Sequence analysis 4Sequence variants 5Unknown
Deletion/duplication analysis 6Exon or whole-gene deletions & duplicationsSee footnote 7
1\.
See Table A. Genes and Databases for chromosome locus and protein.
2\.
See Molecular Genetics for information on allelic variants.
3\.
The ability of the test method used to detect a variant that is present in the indicated gene.
4\.
Examples of pathogenic variants detected by sequence analysis may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.
5\.
For alleles associated with ATP8B1 deficiency in different populations, see Molecular Genetics and Pauli-Magnus et al [2005].
6\.
Testing that identifies exon or whole-gene deletions/duplications not readily detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA; included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.
7\.
Exon and multiexon deletions have been reported in affected individuals (see Table A, HGMD).
### Testing Strategy
To confirm/establish the diagnosis of ATP8B1 deficiency in a proband
1.
Standard clinical-biochemistry tests in cholestasis, including serum γ-GT activity, serum cholesterol concentration, and serum bile acid concentration. Cholestasis, as manifest by direct hyperbilirubinemia and/or hypercholanemia, in the setting of a normal to low γ-GT for age suggests ATP8B1 or ABCB11 deficiency (see Differential Diagnosis). Absence of pruritus and/or near normal serum bile acid concentrations suggests a bile acid synthesis or conjugation defect.
Notes: Bilirubin levels may not be an accurate marker of cholestasis. Substantially elevated aminotransferase activity values at presentation with progressive familial intrahepatic cholestasis (PFIC) suggest ABCB11 deficiency rather than ATP8B1 deficiency [Pawlikowska et al 2010].
2.
FAB-MS analysis of urine to evaluate for a defect in bile acid synthesis or conjugation
3.
Liver biopsy before initiation of ursodeoxycholic acid (UDCA) therapy (or 2 weeks following withdrawal of UDCA). Liver tissue should be routinely processed and examined by light microscopy. A sample should be primarily fixed for transmission electron microscopy.
Note: Liver biopsy may not be necessary if a sib has been definitively diagnosed or if the proband is from an ethnic group in which the disease is relatively common. Genotyping is essential in these cases as a means of confirming a diagnosis.
4.
Molecular genetic testing
* In certain populations in which specific ATP8B1 pathogenic variants are prevalent (Amish, Inuit; see Molecular Genetics), ATP8B1 sequence analysis can replace steps 2 and 3.
* If biallelic ATP8B1 pathogenic variants have been identified in an affected family member, at-risk sibs can undergo molecular genetic testing; steps 1-3 above are not necessary.
* Molecular genetic testing may include ATP8B1 sequence analysis followed by ATP8B1 deletion/duplication analysis for individuals in whom only one mutated allele is identified by sequencing. Alternatively, a multigene panel that includes ATP8B1 may be available. For an introduction to multigene panels click here. More detailed information for clinicians ordering genetic tests can be found here.
## Clinical Characteristics
### Clinical Description
ATP8B1 deficiency encompasses a phenotypic spectrum ranging from severe through intermediate to mild, based on an individual's clinical findings and laboratory test results, including liver biopsy.
Severe ATP8B1 deficiency is characterized by infantile onset of intermittent cholestasis that progresses to cirrhosis, hepatic failure, and death. Mild ATP8B1 deficiency was initially thought to involve intermittent symptomatic cholestasis with a lack of hepatic fibrosis; however, some persons with clinically diagnosed mild disease have hepatic fibrosis at biopsy. Furthermore, in some persons with ATP8B1 deficiency the clinical findings can span the phenotypic spectrum, shifting over time from the mild end of the spectrum (episodic cholestasis) to the severe end of the spectrum (persistent cholestasis) [van Ooteghem et al 2002].
Extrahepatic disease manifestations. Some individuals with ATP8B1 deficiency (severe or mild) have:
* Sensorineural hearing loss, which can progress with time. Hearing loss is attributed to defects in the composition of membranes of inner ear cilia [Stapelbroek et al 2009, Pawlikowska et al 2010].
* Resistance to parathyroid hormone [Nagasaka et al 2004];
* Pancreatitis or pancreatic exocrine insufficiency [Tygstrup et al 1999, Davit-Spraul et al 2010, Pawlikowska et al 2010, Folvik et al 2012];
* Diarrhea independent of pancreatic insufficiency and of failure to absorb fats appropriately [Davit-Spraul et al 2010, Pawlikowska et al 2010, Folvik et al 2012];
* Kidney stones or other kidney disease [Tygstrup et al 1999, Folvik et al 2012].
Less well-documented extrahepatic manifestations for which patients may be at increased risk include:
* Pneumonia. Because cardiolipin can disrupt surfactant function within pulmonary alveoli and because ATP8B1 depletes cardiolipin, ATP8B1 deficiency could increase the risk for (or severity of) pneumonia by increasing alveolar cardiolipin [Pawlikowska et al 2010, Ray et al 2010].
* Delayed puberty.
#### Severe ATP8B1 Deficiency
Severe ATP8B1 deficiency is characterized by onset of symptoms of cholestasis (pruritus and attacks of jaundice) within the first few months of life. Secondary manifestations such as coagulopathy (due to vitamin K deficiency), malabsorption, and poor weight gain may present earlier than age three months.
Malnutrition plays a role in growth retardation; however, symmetric somatic growth failure and delayed puberty may be manifestations of the systemic nature of ATP8B1 deficiency.
Without surgical intervention (see Management), cirrhosis and evolution to end-stage hepatic failure and death usually ensue before the third decade.
While onset in the first year of life with progression to cirrhosis by the end of the first decade of life is typical in severe ATP8B1 deficiency, variability has been noted, even within a single family [Bourke et al 1996, Bull et al 1999, Klomp et al 2004].
The age and type of symptoms at onset vary among individuals. Affected children typically present in the first year of life with severe pruritus with or without jaundice [Pawlikowska et al 2010]. The onset of pruritus is difficult to pinpoint because detection depends on an infant's ability to scratch in a coordinated manner. Irritability may be an initial manifestation of pruritus in some infants. Some individuals have been treated for long periods for chronic dermatologic conditions because of long-standing pruritus without typical hallmarks of liver disease.
Although children may initially experience episodes of severe cholestasis followed by disease-free intervals, cholestasis eventually becomes nonremitting. Pruritus is typically severe and persistent; jaundice is often intermittent. Pruritus is disproportionately severe for the degree of hyperbilirubinemia, but proportional to the elevation in serum bile acids. Typical features of chronic liver disease, including (but not limited to) those that emanate from complications of portal hypertension, may develop.
Growth retardation becomes evident in early childhood. This may be secondary to nutritional complications of cholestasis, which typically result in weight loss out of proportion to loss of linear growth. Alternatively, symmetric failure to thrive, consistent with a somatic defect in growth, may be manifest [Pawlikowska et al 2010].
Cirrhosis and its attendant complications, including hepatic failure and death, typically ensue in the absence of surgical intervention such as partial biliary diversion or liver transplantation (see Management).
Complications of nutritional deficiencies can result in significant morbidity and mortality, especially hemorrhage secondary to vitamin K deficiency. Specific monitoring for, and treatment of, fat-soluble vitamin (A, D, E, and K) deficiency is essential (see Management).
Prolonged malabsorption of fat-soluble vitamins may lead to easy bruising or bleeding (caused by vitamin K deficiency), rickets (caused by vitamin D deficiency), and neurologic abnormalities (caused by vitamin E deficiency). Episodes of epistaxis (in the absence of a coagulopathy or thrombocytopenia) may occur. Significant skin excoriations, caused by constant scratching, are frequent.
Coarsened, stubby hands and fingers have been reported in individuals with genetically undefined PFIC [Ooi et al 2001]. This feature has been encountered in children with genetically confirmed severe ATP8B1 deficiency [B Shneider, personal observation], as has nail dystrophy [Bourke et al 1996, Klomp et al 2004].
As ATP8B1 is expressed in a broad range of tissues, ATP8B1 deficiency can lead to systemic disease manifestations. Liver-related complications are the major consequences of severe ATP8B1 deficiency in most individuals. Some individuals may also manifest abnormalities of pancreatic and intestinal function [Pawlikowska et al 2010]. These may come more prominently to attention after orthotopic liver transplantation (LTX), as secretory diarrhea, pancreatitis, and persistence of growth retardation [Egawa et al 2002, Lykavieris et al 2003, Knisely 2004, Miyagawa-Hayashino et al 2009, Davit-Spraul et al 2010, Hori et al 2011].
Defects in the composition of membranes of enterocyte microvilli have been reported with ATP8B1 deficiency, and it has been suggested that these underlie diarrhea [Verhulst et al 2010].
Post-transplant steatohepatitis may also occur, and can evolve into cirrhosis [Lykavieris et al 2003, Miyagawa-Hayashino et al 2009, Davit-Spraul et al 2010, Hori et al 2011].
#### Mild ATP8B1 Deficiency
Mild ATP8B1 deficiency is characterized by intermittent episodes of cholestasis, severe pruritus, and jaundice in the absence of extrahepatic bile duct obstruction. Episodes may last from weeks to months. Symptom-free intervals may last from months to years.
In contrast to individuals in whom bouts of cholestasis are induced only by particular triggers known to increase risk of cholestasis (drug exposure, shifts in hormonal milieu [including those resulting from ingestion of contraceptive drugs or from pregnancy], coexistent malignancy), some or all bouts of cholestasis in individuals with mild ATP8B1 deficiency have different or unknown triggers.
In truly mild disease, chronic liver damage does not develop; however, in some individuals, ATP8B1 deficiency initially appears mild, but clinical monitoring over time or detection of fibrosis on liver biopsy indicates disease of intermediate severity [van Ooteghem et al 2002, van Mil et al 2004a].
### Penetrance
Pathogenic variants underlying severe ATP8B1 deficiency are likely fully penetrant; however, variable expressivity may be observed among sibs with the same pathogenic variant(s).
ATP8B1 pathogenic variants that usually confer mild episodic ATP8B1 deficiency can occasionally be found in individuals who have not had cholestasis despite having reached an age by which even mild disease is usually manifest; such findings indicate that such pathogenic variants can be incompletely penetrant [Klomp et al 2004].
### Genotype-Phenotype Correlations
Often, but not always, disease severity can be predicted if a pathogenic variant is known; as may be expected, pathogenic variants likely to severely impair ATP8B1 structure and/or function (e.g., nonsense and frameshift variants and large deletions) are more often found in individuals with severe disease.
Missense variants, which may have lesser impact on ATP8B1 structure/function, are found more commonly in individuals with mild disease [Klomp et al 2004].
The p.Ile661Thr pathogenic variant, which is frequently detected in persons with mild disease and of European descent, appears occasionally to be non-penetrant; however, it is also occasionally found in compound heterozygous form in persons with severe disease [Klomp et al 2004].
Family members with the same ATP8B1 pathogenic variants do not always have disease of the same clinical severity. In addition, clinical severity can change over time: mild disease diagnosed in childhood may progress in adulthood to severe disease.
### Nomenclature
Nomenclature for the conditions described in this GeneReview is in flux: the understanding of disease mechanisms is in transition from reliance on phenotypic features (giving rise to the PFIC and BRIC nomenclature), through the genetic mapping of disease loci (giving rise to the PFIC1 and BRIC1 nomenclature), to the identification of disease genes and the recognition of a continuum of disease severity (giving rise to severe and mild ATP8B1 deficiency nomenclature).
In this review, we have used the term:
* "ATP8B1 deficiency" to encompass the entire spectrum of severity of disease associated with ATP8B1 deficiency.
* "Severe ATP8B1 deficiency" to designate disease that may previously have been termed "progressive familial intrahepatic cholestasis type 1" (PFIC1) or "severe FIC1 (familial intrahepatic cholestasis 1) deficiency." (The gene symbol initially assigned to ATP8B1 was FIC1. The gene symbol ATP8B1 was assigned as understanding of ATPase gene families increased.)
* "Mild ATP8B1 deficiency" to designate disease that may previously have been termed "benign recurrent intrahepatic cholestasis type 1" (BRIC1) or "mild FIC1 (familial intrahepatic cholestasis 1) deficiency."
Severe ATP8B1 deficiency in individuals of Amish ancestry was previously called Byler disease, after the kindred in which PFIC was first described [Clayton et al 1969].
Severe ATP8B1 deficiency in individuals of Inuit ancestry was previously called Greenland childhood cholestasis or Greenland familial cholestasis [Nielsen et al 1986, Ornvold et al 1989, Eiberg & Nielsen 1993].
### Prevalence
The prevalence of ATP8B1 deficiency is unknown. It has been considered rare, but misdiagnosis or imprecise diagnosis may have contributed to underestimation of prevalence.
First described as Byler disease in children of Amish descent [Clayton et al 1969], it has now been reported in individuals of all races and many ethnicities. Outside certain restricted populations (e.g., the Amish and Inuit), no specific population is known to be at a higher risk for ATP8B1 deficiency, although certain mutated alleles are more prevalent in particular populations.
Carrier frequencies for ATP8B1 deficiency are unknown, except for the Greenland Inuit in whom the carrier frequency of the pathogenic variant p.Asp554Asn appears quite high. Population studies indicate that the frequency of this disease allele varies regionally in Greenland; the frequency of the mutated allele is high enough to warrant routine screening, reaching 0.16 in Ittoqqortoormiit, and 0.23 in Kuummiut, both in East Greenland [Eiberg & Nielsen 1993, Eiberg et al 2004, Nielsen & Eiberg 2004, Andersen et al 2006].
## Differential Diagnosis
Differential diagnosis most relevant in suspected ATP8B1 deficiency relates to other forms of cholestatic liver disease typically characterized by low or normal serum γ-GT levels. Low or normal serum γ-GT levels distinguish this group of disorders from the much more common and diffuse differential diagnosis of cholestasis in the setting of an elevated serum γ-GT level. Some individuals are diagnosed with PFIC accompanied by high serum γ-GT levels, and in some such individuals, mutation of ABCB4 (encoding MDR3) has been identified. Elevated serum γ-GT activity generally allows this form of pediatric cholestasis to be distinguished from ATP8B1 deficiency.
Relevant cholestatic liver diseases with low or normal serum γ-GT activity include the following:
ABCB11 deficiency. ABCB11 encodes ABCB11, also known as bile salt export pump (BSEP). Severe ABCB11 deficiency is also called PFIC type 2 (PFIC2); mild ABCB11 deficiency is also called BRIC type 2 (BRIC2). The clinical features of ABCB11 deficiency resemble in large part those of ATP8B1 deficiency; differences that facilitate differential diagnosis are discussed below.
Mutation of ABCB11 can lead to retention of bile salts within hepatocytes and to lack of bile salts within canalicular lumina. The detergent effect of bile salts is required for elution of γ-GT from canalicular walls into bile. Lack of intracanalicular bile salts thus has as a consequence that bile leaking between damaged hepatocytes into plasma does not carry with it eluted γ-GT. Serum γ-GT activity in ABCB11 deficiency thus is not elevated.
Early in disease, histopathologic findings in ABCB11 deficiency differ from those in ATP8B1 deficiency. In the former, retained bile salts within hepatocytes damage intrahepatocytic structures, manifest on histopathologic study of liver tissue as swelling, giant-cell change, and necrosis of hepatocytes. Moderate inflammation, varying degrees of fibrosis and elevations in serum transaminase activity accompany this parenchymal injury [Davit-Spraul et al 2010, Pawlikowska et al 2010]. Accumulations of bile pigment are found in hepatocytes as well as in lumina of bile canaliculi. Ultrastructural study of canalicular bile does not identify coarse granularity [Bull et al 1997]. Immunohistochemical study finds ectoenzymes, like γ-GT, expressed along canalicular walls, while expression of ABCB11 is often deficient. (ABCB11 is usually well expressed along bile canaliculi in ATP8B1 deficiency.)
In severe disease, results of some laboratory studies of serum at disease presentation differ between ATP8B1 and ABCB11 deficiencies. For example, serum transaminase activity values are higher at presentation in children with ABCB11 deficiency, consistent with the histopathologic findings indicating more inflammatory disease [Davit-Spraul et al 2010, Pawlikowska et al 2010]. At disease presentation, serum alkaline phosphatase activity is generally higher in severe ATP8B1 deficiency, while serum albumin, bile acid, and alphafetoprotein concentrations tend to be higher in severe ABCB11 deficiency [Davit-Spraul et al 2010, Pawlikowska et al 2010]. Sweat test results (at presentation or later) are more likely to be abnormal in ATP8B1 deficiency than in ABCB11 deficiency [Pawlikowska et al 2010].
Without normal ABCB11/BSEP function, post-hepatic bile (sampled from gallbladder or at ampulla of Vater) is deficient in bile salts [Emerick et al 2008]. Deficiency of primary bile salts in such bile thus can suggest either ATP8B1 deficiency or ABCB11 deficiency.
ABCB11 is expressed only at the apical (bile-canaliculus) membrane of hepatocytes. Mutation of ABCB11 thus leads to primary effects only within the liver. Those effects, with hepatocyte damage, lead to cholestasis. Secondary effects of cholestasis, such as pruritus and malabsorption, are like those of ATP8B1 deficiency. As expected for a disorder caused by mutation in a gene expressed only in hepatocytes, however, the primary manifestations of ABCB11 deficiency are limited to the liver, and extrahepatic disease manifestations are less common than in ATP8B1 deficiency. For example, while gallstone disease is more common in children with severe ABCB11 deficiency than in those with severe ATP8B1 deficiency, children with ATP8B1 deficiency appear more likely to manifest hearing loss, pancreatic disease, diarrhea, rickets, and poor growth [Davit-Spraul et al 2010, Pawlikowska et al 2010]. In contrast to ATP8B1 deficiency, after LTX in ABCB11 deficiency, diarrhea, pancreatitis, and steatosis of the allograft are not described.
ABCB11 deficiency is associated with hepatobiliary malignancy (both hepatocellular carcinoma and cholangiocarcinoma) in childhood [Knisely et al 2006, Scheimann et al 2007, Strautnieks et al 2008]. A single report of pancreatic adenocarcinoma against a background of ABCB11 deficiency has appeared [Bass et al 2010]. Malignancy is not a reported feature of ATP8B1 deficiency.
Some patients with ABCB11 deficiency who undergo LTX develop antibodies against ABCB11 [Keitel et al 2009, Jara et al 2009, Maggiore et al 2010, Siebold et al 2010]. The proportion of transplanted patients who develop such antibodies is unknown. In some such patients, these antibodies impede ABCB11 function and cholestasis develops. The proportion of such patients also is unknown. Disease ascribed to formation of antibodies against ATP8B1 after LTX in patients with ATP8B1 deficiency has not been reported.
Locus heterogeneity for low γ-GT PFIC and BRIC. Evidence indicates the existence of an additional disease locus (or loci) for low γ-GT PFIC and BRIC. Some individuals diagnosed on clinical and histopathologic evidence as having PFIC or BRIC do not show linkage to either ATP8B1 or ABCB11; others, on sequencing of both of these genes, have no detectable pathogenic variant [Bull et al 1997, Floreani et al 2000, Strautnieks et al 2001]. Mutation of TJP2, implicated in hypercholanemia [Carlton et al 2003], underlies some such instances of low γ-GT PFIC [Sambrotta et al 2014].
Inborn errors of bile acid biosynthesis. Synthesis of cholic and chenodeoxycholic acids (the principal human bile acids) from cholesterol comprises several steps, involving cytoplasmic, mitochondrial, and peroxisomal sites [Bove et al 2000]. Mutation in single genes that encode individual pathway enzymes thus may cause disease [Setchell et al 1998, Honda et al 1999, Bove et al 2000, Clayton et al 2002, Grange et al 2002, Setchell et al 2003]. Precursor bile acids are likely poor substrates for ABCB11 and thus accumulate in hepatocyte cytoplasm where they cause damage; cholestasis ensues. Although lack of primary bile salts in bile (see ABCB11 deficiency) precludes rises in serum γ-GT activity, γ-GT is well expressed along canalicular walls in the livers of such patients. For disorders of bile-acid conjugation, see Familial hypercholanemia.
Familial hypercholanemia (FHC) is a disorder with the hallmark feature of fluctuating, but often extremely elevated, concentrations of bile acids in serum. Affected individuals often manifest pruritus, malabsorption of fat-soluble vitamins, and failure to thrive. Most do not become jaundiced. Causative pathogenic variants in four genes, TJP2, BAAT, SLC27A5, and EPHX1, have been identified [Carlton et al 2003, Zhu et al 2003, Chong et al 2012]. BAAT and SLC27A5 encode enzymes involved in bile acid conjugation. Defects in bile acid conjugation can be identified by MS-FAB analysis of urine. Non-conjugated bile acids are poor substrates for ABCB11; they also can traverse cell membranes more readily than can conjugated bile acids. Thus, failure of serum γ-GT to rise in BAAT deficiency and SLC27A5 deficiency likely results from lack of detergent activity in canalicular bile. TJP2 is a scaffold protein in tight junctions, and the reported pathogenic variant is proposed to increase the permeability of tight junctions with regard to bile acids. EPHX1 is implicated in hepatocyte uptake of bile acids from plasma.
Smith-Lemli-Opitz syndrome (SLOS) can secondarily lead to low γ-GT cholestasis [Grange et al 2002] via decreased synthesis of bile acid precursors. SLOS can be diagnosed biochemically through measurement of serum concentrations of dehydrocholesterol and cholesterol.
Nonspecific failure of bile acid production. As in adulthood [Kajiwara et al 1991], acute hepatic failure in infancy can be associated with low γ-GT cholestasis, which is ascribed to nonspecific failure of bile acid production. In this situation, as in primary defects of bile acid synthesis, the detergent effect of bile acids is lacking. Thus, γ-GT is not likely to be eluted by bile from the surface membranes of cells in contact with bile and cannot reflux into plasma. Currently, acute and severe neonatal liver disease is not a known presentation of genetically documented ATP8B1 or ABCB11 deficiency; malabsorption-associated failure to synthesize proteins that require vitamin K as a cofactor must be distinguished from hepatocellular loss and failure to synthesize a broader range of proteins such as albumin and transferrin.
Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is an autosomal recessive condition characterized by Fanconi-type aminoaciduria, degeneration of anterior horn cells (i.e., lower motor neurons), conjugated hyperbilirubinemia without elevated γ-GT, and ichthyosis [Eastham et al 2001]. Pathogenic variants in VPS33B and VIPAR have been identified in individuals with ARC syndrome [Gissen et al 2004, Cullinane et al 2010]. In general, the extrahepatic findings strongly suggest the diagnosis [Bull et al 2006]. The proteins encoded by VPS33B and VIPAR subserve trafficking of various species, including γ-GT and ABCB11, to the canalicular membrane. Failure of γ-GT activity to rise in ARC syndrome, despite cholestasis, thus likely is multifactorial.
Microvillus inclusion disease (MVID). Pathogenic variants in MYO5B underlie this disorder of intracellular trafficking in which apical membranes of enterocytes in particular are poorly assembled [Müller et al 2008]. In individuals with MVID usual microvillus-lined inclusions are not seen in apical cytoplasm of hepatocytes. Evidence for abnormal composition or population of hepatocellular apical membranes, however, is provided by poor expression of γ-GT along bile canaliculi [Peters et al 2001; AS Knisely, personal observations]. Cholestasis in MVID is most often precipitated by parenteral alimentation but also may occur after small-bowel transplantation. In both settings, abnormal composition of canalicular membranes likely increases susceptibility to cholestasis, with failure of γ-GT to rise reflecting lack of γ-GT expression.
Drug-induced cholestasis and intrahepatic cholestasis of pregnancy (ICP). Cholestasis with symptoms like those of ATP8B1 deficiency may develop on exposure to a drug (including contraceptive drugs); cholestasis generally improves when the implicated drug is withdrawn. Similarly, the altered hormonal milieu and/or greater physiologic demands of pregnancy induce some women to develop intrahepatic cholestasis of pregnancy (ICP), in which symptoms typically appear during the third trimester and resolve after delivery. ICP is characterized by cholestasis manifest as pruritus with elevated serum bile acid levels, occasionally accompanied by jaundice. ICP confers an increased risk of fetal complications. Women with ICP generally do not experience symptoms between pregnancies and do not develop chronic liver damage. The frequency with which mutation of ATP8B1 predisposes to drug-induced cholestasis is not known.
Malignancy. Cholestasis with symptoms like those of ATP8B1 deficiency may rarely develop in association with malignancy (paraneoplastic cholestasis). This phenomenon should be borne in mind when evaluating intrahepatic cholestasis that is first manifest after infancy. Instances of paraneoplastic cholestasis associated with mutation of ATP8B1 are not yet described.
## Management
### Evaluations at Initial Diagnosis
To establish the extent of hepatobiliary disease and needs in an individual diagnosed with ATP8B1 deficiency, the authors recommend the following:
* Standard biochemical assays of hepatocellular function and of hepatobiliary injury
* Imaging studies of the liver, with liver biopsy if indicated by the findings on imaging studies or biochemical assays
* Assessment for evidence of portal hypertension to weigh implications for surgical intervention
### Treatment of Manifestations
#### Pharmacologic Therapy
Severe ATP8B1 deficiency. Although various medical therapies to alleviate symptoms and to stop or reverse the progression of liver damage have been tried, this disorder has, for the most part, been refractory to pharmacologic treatment. Standard treatments for pruritus associated with cholestasis (including choleretic agents such as phenobarbital and ursodeoxycholic acid [UDCA], cholestyramine, rifampin, antihistamines, carbamazepine, UV-B light therapy, and plasmapheresis) have been relatively ineffective in the long term. In addition, no data suggest that these therapies alter progression to end-stage liver disease.
Mild ATP8B1 deficiency. Some medications, including rifampicin, UDCA, and bile acid binding resin [Folvik et al 2012, Mizuochi et al 2012, Uegaki et al 2008] may have some efficacy.
#### Nutritional Therapy and Supplementation
Severe ATP8B1 deficiency
* Special attention must be paid to nutritional therapy which includes infant formulas with significant proportions of medium chain triglycerides, which can be absorbed relatively independent of bile flow.
* Nasogastric tube feeding has been useful in some infants.
* Fat-soluble vitamin supplementation using special preparations of vitamin E (e.g., tocopheryl polyethylene glycol-1000 succinate) is useful in severe cholestasis. Individual supplementation may be required to insure adequate levels of fat-soluble vitamins.
#### Other Approaches
Mild ATP8B1 deficiency. Additional temporary approaches such as nasobiliary drainage [Stapelbroek et al 2006, Toros et al 2012] and extracorporeal liver support therapy [Huster et al 2001, Saich et al 2005, Walensi et al 2012] may hasten the end of an episode of cholestasis. Note: Because some of these studies involved individuals with a clinical – but not a molecular – diagnosis of BRIC, it is uncertain whether their disease was the result of pathogenic variants in ATP8B1 or in a different gene.
Interruption of the enterohepatic circulation of bile acids. Since liver damage in severe ATP8B1 deficiency is thought to result from a build-up of bile acids in the liver, surgical interruption of the enterohepatic circulation of bile acids has been used as therapy. Such surgery can successfully reduce pruritus, with slowed or even reversed progression to hepatic fibrosis in some individuals [Felberbauer et al 2000, van Ooteghem et al 2002].
Surgical approaches reported to be successful in severe disease include [Hollands et al 1998, Ismail et al 1999, Rebhandl et al 1999, Melter et al 2000, Bustorff-Silva et al 2007, Clifton et al 2011]:
* Partial external biliary diversion (PEBD) in which the gallbladder apex is anastomosed to one end of a segment of bowel while the other end is used to create a cutaneous stoma from which bile is then drained and discarded*, interrupts the enterohepatic circulation of bile acids and reduces pruritus. In some individuals it even slows or reverses progression to hepatic fibrosis.
*PEBD includes cutaneous cholecystostomy, cholecysto-jejuno-cutaneostomy, cholecysto-appendico-cutaneostomy.
* The internal biliary bypass approach of cholecystojejunocolic anastomosis.
Alternative surgical procedures include ileal exclusion, external diversion with a button device, and biliary diversion to the colon.
Note: Which surgical procedure is most helpful in severe ATP8B1 deficiency is unknown, although PEBD is the most commonly performed surgery. As most studies of responses to these procedures in individuals diagnosed with PFIC [Kaliciński et al 2003, Kurbegov et al 2003] have been performed in genetically uncharacterized patients, differences in response that may depend on which gene is mutated or on the severity of the functional effects of different pathogenic variants have not been assessed.
Liver transplantation (LTX). Individuals with severe ATP8B1 deficiency whose liver disease progresses to decompensated cirrhosis, may require LTX for long-term survival. Individuals whose disease does not respond to surgical interruption of the enterohepatic circulation may also be candidates for LTX.
In some individuals with severe ATP8B1 deficiency, LTX constitutes definitive therapy; however, in others secretory diarrhea in the absence of steatorrhea continues or worsens after LTX [Knisely 2004, Lykavieris et al 2003]. The diarrhea can be severe and may require intravenous fluid administration. Bile acid chelators [Egawa et al 2002] may ameliorate diarrhea after LTX, as they may divert bile produced by the allograft away from the native gut [Usui et al 2009, Nicastro et al 2012]. Clonidine has palliated diarrhea after LTX in some patients [Kocoshis et al 2005].
Somatic growth failure can occur and may not be responsive to LTX.
Pancreatitis and steatohepatitis can occur after otherwise successful LTX [Egawa et al 2002, Lykavieris et al 2003, Miyagawa-Hayashino et al 2009, Davit-Spraul et al 2010, Hori et al 2011]. Steatohepatitis can be progressive and lead to cirrhosis. Both steatosis and diarrhea may respond when PEBD is used to divert the flow of bile from the allograft away from the native gut (which expresses functionally defective ATP8B1) [Usui et al 2009, Nicastro et al 2012].
Extrahepatic manifestations. Persons with sensorineural hearing loss may require hearing aids [Stapelbroek et al 2009, Pawlikowska et al 2010].
### Prevention of Primary Manifestations
Severe ATP8B1 deficiency. Surgical interruption of the enterohepatic circulation should be the primary therapy in individuals with severe ATP8B1 deficiency unless cirrhosis is present, in which case LTX should be considered.
Mild ATP8B1 deficiency. LTX appears difficult to justify in patients with mild, intermittently manifesting ATP8B1 deficiency. The role of surgical interruption of the enterohepatic circulation in mild ATP8B1 deficiency is unclear.
### Prevention of Secondary Complications
Fat-soluble vitamin supplementation is a key aspect of the management of the cholestasis seen in ATP8B1 deficiency. Vitamin supplementation is necessary to alleviate malabsorption of fat-soluble vitamins. Vitamin K administration in the newborn period is of critical importance.
Medium chain triglyceride based formulas may be useful in the prevention and/or treatment of growth failure.
### Surveillance
Periodic monitoring for fat-soluble vitamin deficiency is recommended.
Hearing screening is recommended at five-year intervals in individuals with no symptomatic evidence of hearing deficits.
Monitoring for hepatobiliary malignancy has not been shown to be necessary in ATP8B1 deficiency.
### Agents/Circumstances to Avoid
Susceptibility to sensorineural hearing loss in ATP8B1 deficiency may argue against use of aminoglycoside antibiotics or other potentially ototoxic agents.
### Evaluation of Relatives at Risk
See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.
### Therapies Under Investigation
Administration of 4-phenylbutyrate, a modifier of protein configuration, has improved expression/function of ATP8B1 in vitro [van der Velden et al 2010]. Extension to clinical use is under study [Gonzales & Jacquemin 2010].
Search ClinicalTrials.gov in the US and www.ClinicalTrialsRegister.eu in Europe for access to information on clinical studies for a wide range of diseases and conditions.
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
ATP8B1 Deficiency
|
c4551898
| 7,398 |
gene_reviews
|
https://www.ncbi.nlm.nih.gov/books/NBK1297/
| 2021-01-18T21:44:11 |
{"mesh": ["C535933"], "synonyms": ["FIC1 Deficiency"]}
|
Hürthle cell
Other namesAskanazy cell
Micrograph showing Hürthle cells in a Hürthle cell neoplasm. Pap stain.
Pronunciation
* /ˈhɪərtlə/
SpecialtyPathology
A Hürthle cell is a cell in the thyroid that is often associated with Hashimoto's thyroiditis[1] as well as benign and malignant tumors (Hürthle cell adenoma and Hürthle cell carcinoma,[2] formerly considered a subtype of follicular thyroid cancer). This version is a relatively rare form of differentiated thyroid cancer, accounting for only 3-10% of all differentiated thyroid cancers.[3] Oncocytes in the thyroid are often called Hürthle cells. Although the terms oncocyte, oxyphilic cell, and Hürthle cell are used interchangeably, Hürthle cell is used only to indicate cells of thyroid follicular origin.[4]
## Contents
* 1 Diseases
* 2 Diagnosis
* 3 Histology
* 4 Treatment
* 5 History
* 6 See also
* 7 References
* 8 External links
## Diseases[edit]
Hürthle cell tumors can be separated into Hürthle cell adenoma and carcinomas, which are respectively benign and malignant tumors arising from the follicular epithelium of the thyroid gland.[5] The mitochondrial DNA of Hürthle cell carcinoma contain somatic mutations.[5] Hürthle cell carcinomas consists of at least 75% Hürthle cells.[6] Chronic lymphocytic thyroiditis or Hashimoto's thyroiditis, along with cases of long-standing Graves' disease, show Hürthle cells present.[4]
## Diagnosis[edit]
Hürthle cell adenomas are most likely diagnosed much more frequently than Hürthle cell carcinomas. The female to male ratio for Hurthle cell adenomas is 8:1, while the ratio is 2:1 for the malignant version.[5] Hürthle cell cancer tends to occur in older patients. The median age at diagnosis for Hürthle cell carcinomas is approximately 61 years old.[5] Typically a painless thyroid mass is found in patients with this type of cancer.[5] As expected, patients with carcinoma usually present larger tumors than patients with adenoma. Rarely, the cancer can spread to the lymph nodes.[6] On few occasions, patients with Hürthle cell carcinoma have distant metastases in the lungs or surrounding bones.[5] Hürthle cell neoplasms are somewhat difficult to differentiate between being benign or malignant. Since the size and growth pattern of the tumor cannot be used to determine malignancy, although larger tumors have higher incidence of malignancy, Hürthle cell adenomas and carcinomas have to be separated by the presence, in the case of carcinomas, or absence, in the case of adenomas, of both capsular invasion and vascular invasion.[5] Tumors displaying only capsular invasion tend to behave less aggressively than those with vascular invasion.[7] Hürthle cell carcinomas are characterized as either minimally invasive or widely invasive tumors. While the minimally invasive or encapsulated carcinoma is fully surrounded by a fibrous capsule, the widely invasive carcinoma shows extensive area of both capsular and vascular invasion with the leftover capsule typically difficult to identify.[5] Classification is important since widely invasive tumors can have outcomes with a 55% mortality rate.[5]
## Histology[edit]
Hürthle cells arise from the follicular epithelium. Key features of these oncocytic cells include an eosinophilic granular cytoplasm and a vesicular nucleus with a large nucleolus.[5] A Hürthle cell is larger than a follicular cell, and its cellular material stains pink. Hürthle cells also tend to be large, polygonal cells with distinct cell borders.[4] The cytoplasm of the oncocytes in Hürthle cell adenomas and carcinomas is characterized by an eosinophilic granular nature, which is commonly due to the oncocytes' high content of mitochondria.[5] Some of these cells can contain up to 5,000 mitochondria, which fills the cytoplasm to the point of nearly excluding other organelles.[4] This high amount of mitochondria is reported to be a result of mutations in the mitochondrial DNA.[4] Some scientists have identified these mutations as deletions in the mitochondrial DNA of Hürthle cells found in neoplasms and Hashimoto's thyroiditis.[6]
## Treatment[edit]
A non-minimally invasive Hürthle cell carcinoma is typically treated by a total thyroidectomy followed by radioactive iodine therapy.[5] A Hürthle cell adenoma or a minimally invasive tumor can be treated by a thyroid lobectomy, although some surgeons will perform a total thyroidectomy to prevent the tumor from reappearing and metastasizing.[5] A modified radical neck dissection may be performed for clinically positive lymph nodes.
## History[edit]
The Hürthle cell is named after German histologist Karl Hürthle, who investigated thyroid secretory function, particularly in dogs.[8] However, this is a misnomer since Hürthle actually described parafollicular C cells.[4] The cell known as the Hürthle cell was first described in 1898 by Max Askanazy, who noted it in patients with Graves' disease.[4][9]
## See also[edit]
* Adenoma
* Oncocytoma
* Oxyphil cell
## References[edit]
1. ^ "Endocrine Pathology". Retrieved 2009-05-07.
2. ^ Grani, Giorgio; Lamartina, Livia; Durante, Cosimo; Filetti, Sebastiano; Cooper, David S (2018). "Follicular thyroid cancer and Hürthle cell carcinoma: challenges in diagnosis, treatment, and clinical management". The Lancet Diabetes & Endocrinology. 6 (6): 500–514. doi:10.1016/s2213-8587(17)30325-x. PMID 29102432.
3. ^ Aytug, Serhat (June 13, 2006). "Hurthle Cell Carcinoma". eMedicine. Cite journal requires `|journal=` (help)
4. ^ a b c d e f g Cannon, J. (2011). The Significance of Hurthle Cells in Thyroid Disease. The Oncologist. doi:10.1634/theoncologist.2010-0253
5. ^ a b c d e f g h i j k l m Schwab, M. (2011). Encyclopedia of Cancer. Encyclopedia of Cancer. doi:10.1016/B0-12-227555-1/00151-9
6. ^ a b c Montone, Kathleen T., Zubair W. Baloch, and Virginia A. LiVolsi. "The thyroid Hurthle (oncocytic) cell and its associated pathologic conditions: a surgical pathology and cytopathology review." Archives of Pathology and Laboratory Medicine 132.8 (2008): 1241-1250.
7. ^ Erickson, Lori A. "Hurthle Cell Thyroid Neoplasms." Atlas of Endocrine Pathology. Springer New York, 2014. 63-66.
8. ^ Hürthle, Karl (1894). "Beitrage zur Kenntnis des Sekretionsvorgangs in der Schilddruse". Archiv für die gesamte Physiologie des Menschen und der Tiere. 56: 10–44. doi:10.1007/bf01662011.
9. ^ M. Askanazy. Pathologisch-anatomische Beiträge zur Kenntniss des morbus basedowii, insbesondere uber die dabei auftretende Muskelerkrankkung. Deutsches Archiv für klinische Medicin, Leipzig, 1898, 61:118-186.
## External links[edit]
Classification
D
* ICD-10: C73.9
* ICD-O: 8290/0
* MeSH: D018249
* DiseasesDB: 31956
External resources
* eMedicine: med/1045
* EndocrineWeb at endocrineweb.com
* HKU at hku.hk
* Image at upmc.edu
* v
* t
* e
Glandular and epithelial cancer
Epithelium
Papilloma/carcinoma
* Small-cell carcinoma
* Combined small-cell carcinoma
* Verrucous carcinoma
* Squamous cell carcinoma
* Basal-cell carcinoma
* Transitional cell carcinoma
* Inverted papilloma
Complex epithelial
* Warthin's tumor
* Thymoma
* Bartholin gland carcinoma
Glands
Adenomas/
adenocarcinomas
Gastrointestinal
* tract: Linitis plastica
* Familial adenomatous polyposis
* pancreas
* Insulinoma
* Glucagonoma
* Gastrinoma
* VIPoma
* Somatostatinoma
* Cholangiocarcinoma
* Klatskin tumor
* Hepatocellular adenoma/Hepatocellular carcinoma
Urogenital
* Renal cell carcinoma
* Endometrioid tumor
* Renal oncocytoma
Endocrine
* Prolactinoma
* Multiple endocrine neoplasia
* Adrenocortical adenoma/Adrenocortical carcinoma
* Hürthle cell
Other/multiple
* Neuroendocrine tumor
* Carcinoid
* Adenoid cystic carcinoma
* Oncocytoma
* Clear-cell adenocarcinoma
* Apudoma
* Cylindroma
* Papillary hidradenoma
Adnexal and
skin appendage
* sweat gland
* Hidrocystoma
* Syringoma
* Syringocystadenoma papilliferum
Cystic, mucinous,
and serous
Cystic general
* Cystadenoma/Cystadenocarcinoma
Mucinous
* Signet ring cell carcinoma
* Krukenberg tumor
* Mucinous cystadenoma / Mucinous cystadenocarcinoma
* Pseudomyxoma peritonei
* Mucoepidermoid carcinoma
Serous
* Ovarian serous cystadenoma / Pancreatic serous cystadenoma / Serous cystadenocarcinoma / Papillary serous cystadenocarcinoma
Ductal, lobular,
and medullary
Ductal carcinoma
* Mammary ductal carcinoma
* Pancreatic ductal carcinoma
* Comedocarcinoma
* Paget's disease of the breast / Extramammary Paget's disease
Lobular carcinoma
* Lobular carcinoma in situ
* Invasive lobular carcinoma
Medullary carcinoma
* Medullary carcinoma of the breast
* Medullary thyroid cancer
Acinar cell
* Acinic cell carcinoma
* v
* t
* e
Tumours of endocrine glands
Pancreas
* Pancreatic cancer
* Pancreatic neuroendocrine tumor
* α: Glucagonoma
* β: Insulinoma
* δ: Somatostatinoma
* G: Gastrinoma
* VIPoma
Pituitary
* Pituitary adenoma: Prolactinoma
* ACTH-secreting pituitary adenoma
* GH-secreting pituitary adenoma
* Craniopharyngioma
* Pituicytoma
Thyroid
* Thyroid cancer (malignant): epithelial-cell carcinoma
* Papillary
* Follicular/Hurthle cell
* Parafollicular cell
* Medullary
* Anaplastic
* Lymphoma
* Squamous-cell carcinoma
* Benign
* Thyroid adenoma
* Struma ovarii
Adrenal tumor
* Cortex
* Adrenocortical adenoma
* Adrenocortical carcinoma
* Medulla
* Pheochromocytoma
* Neuroblastoma
* Paraganglioma
Parathyroid
* Parathyroid neoplasm
* Adenoma
* Carcinoma
Pineal gland
* Pinealoma
* Pinealoblastoma
* Pineocytoma
MEN
* 1
* 2A
* 2B
*[v]: View this template
*[t]: Discuss this template
*[e]: Edit this template
*[c.]: circa
*[AA]: Adrenergic agonist
*[AD]: Acetaldehyde dehydrogenase
*[HAART]: highly active antiretroviral therapy
*[Ki]: Inhibitor constant
*[nM]: nanomolars
*[MOR]: μ-opioid receptor
*[DOR]: δ-opioid receptor
*[KOR]: κ-opioid receptor
*[SERT]: Serotonin transporter
*[NET]: Norepinephrine transporter
*[NMDAR]: N-Methyl-D-aspartate receptor
*[M:D:K]: μ-receptor:δ-receptor:κ-receptor
*[ND]: No data
*[NOP]: Nociceptin receptor
*[BMI]: body mass index
*[OCD]: Obsessive-compulsive disorder
*[SSRIs]: Selective serotonin reuptake inhibitors
*[SNRIs]: Serotonin–norepinephrine reuptake inhibitor
*[TCAs]: Tricyclic antidepressants
*[MAOIs]: Monoamine oxidase inhibitors
*[MSNs]: medium spiny neurons
*[CREB]: cAMP response element-binding protein
*[NC]: neurogenic claudication
*[LSS]: lumbar spinal stenosis
*[DDD]: degenerative disc disease
*[CI]: confidence interval
*[E2]: estradiol
*[CEEs]: conjugated estrogens
*[Diff]: Difference
*[7d avg]: Average of the last 7 days
*[per 100k pop]: Deaths per 100,000 population using 10.12 Million as Sweden's total population
*[Cases per 100k]: Cases per 100,000 county population
*[Deaths per 100k]: Deaths per 100,000 county population
*[Percent]: Percent of total in category
*[Rate]: ICU-care cases per confirmed cases in each category
*[GER]: Germany
*[FRA]: France
*[ITA]: Italy
*[ESP]: Spain
*[DEN]: Denmark
*[SUI]: Switzerland
*[USA]: United States
*[COL]: Colombia
*[KAZ]: Kazakhstan
*[NED]: Netherlands
*[LIT]: Lithuania
*[POR]: Portugal
*[AUT]: Austria
*[AUS]: Australia
*[RUS]: Russia
*[LUX]: Luxembourg
*[UKR]: Ukraine
*[SLO]: Slovenia
*[GBR]: Great Britain
*[CZE]: Czech Republic
*[BEL]: Belgium
*[CAN]: Canada
*[DHT]: dihydrotestosterone
*[IM]: intramuscular injection
*[SC]: subcutaneous injection
*[MRIs]: monoamine reuptake inhibitors
*[GHB]: γ-hydroxybutyric acid
*[pop.]: population
*[et al.]: et alia (and others)
*[a.k.a.]: also known as
*[mRNA]: messenger RNA
*[kDa]: kilodalton
*[EPC]: Early Prostate Cancer
*[LAPC]: locally advanced prostate cancer
*[NSAAs]: nonsteroidal antiandrogens
*[NSAA]: nonsteroidal antiandrogen
*[GnRH]: gonadotropin-releasing hormone
*[ADT]: androgen deprivation therapy
*[LH]: luteinizing hormone
*[AR]: androgen receptor
*[CAB]: combined androgen blockade
*[LPC]: localized prostate cancer
*[CPA]: cyproterone acetate
*[U.S.]: United States
*[FDA]: Food and Drug Administration
|
Hürthle cell
|
c0949541
| 7,399 |
wikipedia
|
https://en.wikipedia.org/wiki/H%C3%BCrthle_cell
| 2021-01-18T18:42:25 |
{"mesh": ["D018249"], "umls": ["C0949541"], "icd-10": ["C73.9"], "wikidata": ["Q4223446"]}
|
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