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wikipedia | https://en.wikipedia.org/wiki/Diastrophic_dysplasia | YJWxNNZ | Diastrophic dysplasia | C1857255 | 10 | diastrophic dysplasia. itila I, Weiffenbach B, Kidd KK, De La Chapelle A (December 1991). "A linkage map spanning the locus for diastrophic dysplasia (DTD)". Genomics. 11 (4): 968–973. doi:10.1016/0888-7543(91)90021-6. PMID 1783404.
^ "diastrophic - Definition from the Merriam-Webster Online Dictionary". Retrieved 2009-03-12.
This article incorporates some public domain text from The U.S. National Library of Medicine
External links
ClassificationDICD-10: Q77.5OMIM: 222600MeSH: C536170 C536170, C536170DiseasesDB: 30759External resourceseMedicine: orthoped/632Orphanet: 628
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wikipedia | https://en.wikipedia.org/wiki/Diastrophic_dysplasia | YJWxNNZ | Diastrophic dysplasia | C1857255 | 10 | diastrophic dysplasia. Webster Online Dictionary". Retrieved 2009-03-12.
This article incorporates some public domain text from The U.S. National Library of Medicine
External links
ClassificationDICD-10: Q77.5OMIM: 222600MeSH: C536170 C536170, C536170DiseasesDB: 30759External resourceseMedicine: orthoped/632Orphanet: 628
GeneReviews/NCBI/NIH/UW entry on Diastrophic Dysplasia
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wikipedia | https://en.wikipedia.org/wiki/Diastrophic_dysplasia | YJWxNNZ | Diastrophic dysplasia | C1857255 | 10 | diastrophic dysplasia. NIH/UW entry on Diastrophic Dysplasia
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wikipedia | https://en.wikipedia.org/wiki/Diastrophic_dysplasia | YJWxNNZ | Diastrophic dysplasia | C1857255 | 10 | diastrophic dysplasia. -variant:small-caps;border-bottom:none;text-decoration:none;cursor:inherit}.mw-parser-output .navbar-ct-full{font-size:114%;margin:0 7em}.mw-parser-output .navbar-ct-mini{font-size:114%;margin:0 4em}.mw-parser-output .infobox .navbar{font-size:100%}.mw-parser-output .navbox .navbar{display:block;font-size:100%}.mw-parser-output .navbox-title .navbar{float:left;text-align:left;margin-right:0.5em}vteOsteochondrodysplasiaOsteodysplasia//osteodystrophyDiaphysis
Camurati–Engelmann disease
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wikipedia | https://en.wikipedia.org/wiki/Diastrophic_dysplasia | YJWxNNZ | Diastrophic dysplasia | C1857255 | 10 | diastrophic dysplasia. obox .navbar{font-size:100%}.mw-parser-output .navbox .navbar{display:block;font-size:100%}.mw-parser-output .navbox-title .navbar{float:left;text-align:left;margin-right:0.5em}vteOsteochondrodysplasiaOsteodysplasia//osteodystrophyDiaphysis
Camurati–Engelmann disease
Metaphysis
Metaphyseal dysplasia
Jansen's metaphyseal chondrodysplasia
Schmid metaphyseal chondrodysplasia
Epiphysis
Spondyloepiphyseal dysplasia congenita
Multiple epiphyseal dysplasia
Otospondylomegaepiphyseal dysplasia
Osteosclerosis
Raine syndrome
Osteopoikilosis
Osteopetrosis
Other/ungrouped
FLNB
Boomerang dysplasia
Opsismodysplasia
Polyostotic fibrous dysplasia
McCune–Albright syndrome
Chondrodysplasia/chondrody | [
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] |
wikipedia | https://en.wikipedia.org/wiki/Diastrophic_dysplasia | YJWxNNZ | Diastrophic dysplasia | C1857255 | 10 | diastrophic dysplasia. Engelmann disease
Metaphysis
Metaphyseal dysplasia
Jansen's metaphyseal chondrodysplasia
Schmid metaphyseal chondrodysplasia
Epiphysis
Spondyloepiphyseal dysplasia congenita
Multiple epiphyseal dysplasia
Otospondylomegaepiphyseal dysplasia
Osteosclerosis
Raine syndrome
Osteopoikilosis
Osteopetrosis
Other/ungrouped
FLNB
Boomerang dysplasia
Opsismodysplasia
Polyostotic fibrous dysplasia
McCune–Albright syndrome
Chondrodysplasia/chondrodystrophy(including dwarfism)Osteochondroma
osteochondromatosis
Hereditary multiple exostoses
Chondroma/enchondroma
enchondromatosis
Ollier disease
Maffucci syndrome
Growth factor receptorFGFR2:
Antley–Bixler syndrome
FGFR3:
Achondroplasia
Hypochondroplasia
Thanatophoric dysplasia
COL2A1 collagen disease
Achondrogenesis
type 2
Hypochondrogenesis
SLC26A2 sulfation defect
Achondrogenesis
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wikipedia | https://en.wikipedia.org/wiki/Diastrophic_dysplasia | YJWxNNZ | Diastrophic dysplasia | C1857255 | 10 | diastrophic dysplasia. dysplasia/chondrodystrophy(including dwarfism)Osteochondroma
osteochondromatosis
Hereditary multiple exostoses
Chondroma/enchondroma
enchondromatosis
Ollier disease
Maffucci syndrome
Growth factor receptorFGFR2:
Antley–Bixler syndrome
FGFR3:
Achondroplasia
Hypochondroplasia
Thanatophoric dysplasia
COL2A1 collagen disease
Achondrogenesis
type 2
Hypochondrogenesis
SLC26A2 sulfation defect
Achondrogenesis
type 1B
Autosomal recessive multiple epiphyseal dysplasia
Atelosteogenesis, type II
Diastrophic dysplasia
Chondrodysplasia punctata
Rhizomelic chondrodysplasia punctata
Conradi–Hünermann syndrome
Other dwarfism
Fibrochondrogenesis
Short rib – polydactyly syndrome
Majewski's polydactyly syndrome
Léri–Weill dyschondrosteosis
vteGenetic disorder, membrane: Solute carrier disorders1-10
SLC1A3
Episodic ataxia 6
SLC2A1 | [
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] |
wikipedia | https://en.wikipedia.org/wiki/Diastrophic_dysplasia | YJWxNNZ | Diastrophic dysplasia | C1857255 | 10 | diastrophic dysplasia. ation defect
Achondrogenesis
type 1B
Autosomal recessive multiple epiphyseal dysplasia
Atelosteogenesis, type II
Diastrophic dysplasia
Chondrodysplasia punctata
Rhizomelic chondrodysplasia punctata
Conradi–Hünermann syndrome
Other dwarfism
Fibrochondrogenesis
Short rib – polydactyly syndrome
Majewski's polydactyly syndrome
Léri–Weill dyschondrosteosis
vteGenetic disorder, membrane: Solute carrier disorders1-10
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 | [
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wikipedia | https://en.wikipedia.org/wiki/Diastrophic_dysplasia | YJWxNNZ | Diastrophic dysplasia | C1857255 | 10 | diastrophic dysplasia. 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
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wikipedia | https://en.wikipedia.org/wiki/Diastrophic_dysplasia | YJWxNNZ | Diastrophic dysplasia | C1857255 | 10 | diastrophic dysplasia. 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
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Cached time: 20210110170123
Cache expiry: 2592000
Dynamic content: false
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Real time usage: 0.477 seconds
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wikipedia | https://en.wikipedia.org/wiki/Diastrophic_dysplasia | YJWxNNZ | Diastrophic dysplasia | C1857255 | 10 | diastrophic dysplasia. red syndrome
SLC35C1
CDOG 2C
SLC39A4
Acrodermatitis enteropathica
SLC40A1
African iron overload
see also solute carrier family
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wikipedia | https://en.wikipedia.org/wiki/Diastrophic_dysplasia | YJWxNNZ | Diastrophic dysplasia | C1857255 | 10 | diastrophic dysplasia. % 89.871 1 Template:Refimprove
20.72% 81.825 1 Template:Infobox_medical_condition_(new)
17.58% 69.428 1 Template:Ambox
16.32% 64.457 1 Template:Medical_resources
10.84% 42.812 2 Template:Hlist
9.52% 37.616 5 Template:Navbox
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wikipedia | https://en.wikipedia.org/wiki/Diastrophic_dysplasia | YJWxNNZ | Diastrophic dysplasia | C1857255 | 10 | diastrophic dysplasia. in parser cache with key enwiki:pcache:idhash:1492129-0!canonical and timestamp 20210110170123 and revision id 995972589. Serialized with JSON.
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omim | https://www.omim.org/entry/260555 | lPLwKPx | PARTINGTON-ANDERSON SYNDROME | C1850075 | 11 | partington-anderson syndrome. In a brother and sister from one family and a girl from a second, unrelated family, Partington and Anderson (1994) described a seemingly new syndrome comprising pre- and postnatal growth deficiency, developmental delay, a friendly personality, microcephaly, and a distinctive facial appearance marked by thick eyebrows, full cheeks, and a short nose with the columella inserted below the nasal alae. They suggested that the disorder is inherited as an autosomal recessive. The parents were not consanguineous in either family. Thick curly hair of the head in infancy may be a feature. | [
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omim | https://www.omim.org/entry/251700 | 2LL4rmG | MICROPHTHALMIA WITH HYPEROPIA, RETINAL DEGENERATION, MACROPHAKIA, AND DENTAL ANOMALIES | C1968637 | 12 | microphthalmia with hyperopia, retinal degeneration, macrophakia, and dental anomalies. In a sibship of 7 without parental consanguinity, Franceschetti and Gernet (1965) found 4 (3 males, 1 female) with marked microphthalmia diagnosed by ultrasound, with cornea of normal size. Associated ocular features were high-grade hyperopia, macrophakia, retinal degeneration reminiscent of fundus albipunctatus (136880) or fundus flavimaculatus (see 248200), hemeralopia, and glaucoma. All 4 affected individuals had extremely poor dentition; the sister had full dentures by 31 years of age.
HEENT
- Microphthalmos
- Normal-sized cornea
- High-grade hypermetropia
- Macrophakia
- Retinal degeneration
- Glaucoma
- Dental anomalies
Inheritance
- Autosomal recessive
▲ Close | [
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omim | https://www.omim.org/entry/251700 | 2LL4rmG | MICROPHTHALMIA WITH HYPEROPIA, RETINAL DEGENERATION, MACROPHAKIA, AND DENTAL ANOMALIES | C1968637 | 12 | microphthalmia with hyperopia, retinal degeneration, macrophakia, and dental anomalies. imaculatus (see 248200), hemeralopia, and glaucoma. All 4 affected individuals had extremely poor dentition; the sister had full dentures by 31 years of age.
HEENT
- Microphthalmos
- Normal-sized cornea
- High-grade hypermetropia
- Macrophakia
- Retinal degeneration
- Glaucoma
- Dental anomalies
Inheritance
- Autosomal recessive
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] |
omim | https://www.omim.org/entry/614009 | rD474Pr | BLEEDING DISORDER, PLATELET-TYPE, 13, SUSCEPTIBILITY TO | C3279614 | 13 | bleeding disorder, platelet-type, 13, susceptibility to. A number sign (#) is used with this entry because susceptibility to this platelet-type bleeding disorder (BDPLT13) is conferred by heterozygous mutation in the gene encoding the thromboxane A2 receptor (TBXA2R; 188070) on chromosome 19p13.
Description
Susceptibility to platelet-type bleeding disorder-13 is due to a defective thromboxane A2 receptor on platelets. The susceptibility is inherited in an autosomal dominant pattern, but clinical features, including mild mucocutaneous bleeding, occur only in the presence of a 'second hit' affecting platelet function; this second hit may be either in the TBXA2R gene or in another gene affecting the coagulation cascade (summary by Mumford et al., 2010).
Clinical Features
Weiss and Lages (1977) reported a 10-year-old boy with easy bruising and excessive bleeding after a tooth extraction at age 2 years. Laboratory studies showed normal platelet counts | [
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] |
omim | https://www.omim.org/entry/614009 | rD474Pr | BLEEDING DISORDER, PLATELET-TYPE, 13, SUSCEPTIBILITY TO | C3279614 | 13 | bleeding disorder, platelet-type, 13, susceptibility to. clinical features, including mild mucocutaneous bleeding, occur only in the presence of a 'second hit' affecting platelet function; this second hit may be either in the TBXA2R gene or in another gene affecting the coagulation cascade (summary by Mumford et al., 2010).
Clinical Features
Weiss and Lages (1977) reported a 10-year-old boy with easy bruising and excessive bleeding after a tooth extraction at age 2 years. Laboratory studies showed normal platelet counts, but defective second phase platelet aggregation in response to epinephrine or ADP. Addition of platelet-rich plasma from a normal person who had ingested aspirin resulted in platelet aggregation, indicating that the defect was not in cyclooxygenase (PTGS1; 176805). Addition of prostaglandin G2 did not result in patient platelet aggregation, suggesting a defect in the production of or response to thromboxane A2. Weiss and Lages (1977) postulated a | [
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omim | https://www.omim.org/entry/614009 | rD474Pr | BLEEDING DISORDER, PLATELET-TYPE, 13, SUSCEPTIBILITY TO | C3279614 | 13 | bleeding disorder, platelet-type, 13, susceptibility to. a tooth extraction at age 2 years. Laboratory studies showed normal platelet counts, but defective second phase platelet aggregation in response to epinephrine or ADP. Addition of platelet-rich plasma from a normal person who had ingested aspirin resulted in platelet aggregation, indicating that the defect was not in cyclooxygenase (PTGS1; 176805). Addition of prostaglandin G2 did not result in patient platelet aggregation, suggesting a defect in the production of or response to thromboxane A2. Weiss and Lages (1977) postulated a defect in thromboxane synthesis (TBXAS1; 274180). However, in a follow-up study, Lages et al. (1981) found that the patient's platelets did not aggregate in response to TBXAS1 generated from arachidonic acid in normal platelets, but were capable of synthesizing thromboxane from both arachidonic acid and prostaglandin G2. Patient platelets also showed a defect in mobilization of intracellular calcium. Overall, the findings indicated that | [
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omim | https://www.omim.org/entry/614009 | rD474Pr | BLEEDING DISORDER, PLATELET-TYPE, 13, SUSCEPTIBILITY TO | C3279614 | 13 | bleeding disorder, platelet-type, 13, susceptibility to. to thromboxane A2. Weiss and Lages (1977) postulated a defect in thromboxane synthesis (TBXAS1; 274180). However, in a follow-up study, Lages et al. (1981) found that the patient's platelets did not aggregate in response to TBXAS1 generated from arachidonic acid in normal platelets, but were capable of synthesizing thromboxane from both arachidonic acid and prostaglandin G2. Patient platelets also showed a defect in mobilization of intracellular calcium. Overall, the findings indicated that the defect in this patient did not result from a thromboxane synthetase deficiency, but may be due to impaired platelet response to thromboxane A2 and impaired mobilization of platelet calcium, consistent with the possibility that thromboxane A2 may act as a calcium ionophore. Ushikubi et al. (1987) and Fuse et al. (1993) reported 2 unrelated patients with a mild bleeding disorder caused by impaired platelet aggregation responses to TBXA2 and | [
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omim | https://www.omim.org/entry/614009 | rD474Pr | BLEEDING DISORDER, PLATELET-TYPE, 13, SUSCEPTIBILITY TO | C3279614 | 13 | bleeding disorder, platelet-type, 13, susceptibility to. a defect in mobilization of intracellular calcium. Overall, the findings indicated that the defect in this patient did not result from a thromboxane synthetase deficiency, but may be due to impaired platelet response to thromboxane A2 and impaired mobilization of platelet calcium, consistent with the possibility that thromboxane A2 may act as a calcium ionophore. Ushikubi et al. (1987) and Fuse et al. (1993) reported 2 unrelated patients with a mild bleeding disorder caused by impaired platelet aggregation responses to TBXA2 and its analogs, despite a normal response to thrombin. Although the patients' platelets exhibited normal binding activities to TXA2 analogs, they showed decreased GTPase activity and second messenger formation when stimulated by a stable TXA2 agonist. Platelets also showed defective intracellular calcium mobilization in response to these stimuli. This led to the proposal that the defect in the patients was due to impaired coupling of TBXA2R to the G protein. Hirata et al. (1994) | [
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] |
omim | https://www.omim.org/entry/614009 | rD474Pr | BLEEDING DISORDER, PLATELET-TYPE, 13, SUSCEPTIBILITY TO | C3279614 | 13 | bleeding disorder, platelet-type, 13, susceptibility to. mild bleeding disorder caused by impaired platelet aggregation responses to TBXA2 and its analogs, despite a normal response to thrombin. Although the patients' platelets exhibited normal binding activities to TXA2 analogs, they showed decreased GTPase activity and second messenger formation when stimulated by a stable TXA2 agonist. Platelets also showed defective intracellular calcium mobilization in response to these stimuli. This led to the proposal that the defect in the patients was due to impaired coupling of TBXA2R to the G protein. Hirata et al. (1994) provided follow-up of the patient reported by Ushikubi et al. (1987). The patient's son, daughter, and brother had a similar, but milder, defect in platelet aggregation in response to a TXA2 agonist. Mumford et al. (2010) reported a 14-year-old white boy with a history of easy bruising and prolonged epistaxis since infancy. Laboratory studies showed lack | [
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] |
omim | https://www.omim.org/entry/614009 | rD474Pr | BLEEDING DISORDER, PLATELET-TYPE, 13, SUSCEPTIBILITY TO | C3279614 | 13 | bleeding disorder, platelet-type, 13, susceptibility to. 2R to the G protein. Hirata et al. (1994) provided follow-up of the patient reported by Ushikubi et al. (1987). The patient's son, daughter, and brother had a similar, but milder, defect in platelet aggregation in response to a TXA2 agonist. Mumford et al. (2010) reported a 14-year-old white boy with a history of easy bruising and prolonged epistaxis since infancy. Laboratory studies showed lack of platelet aggregation in response to low doses of arachidonic acid and impaired aggregation in response to a TBXA2 agonist. Platelets from the father showed a similar pattern, although he had no bleeding symptoms.
Inheritance
Susceptibility to this bleeding disorder due to defective thromboxane A2 receptor is an autosomal dominant trait (Hirata et al., 1994).
Molecular Genetics
In affected members of 2 unrelated families with a bleeding disorder (Ushikubi et | [
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] |
omim | https://www.omim.org/entry/614009 | rD474Pr | BLEEDING DISORDER, PLATELET-TYPE, 13, SUSCEPTIBILITY TO | C3279614 | 13 | bleeding disorder, platelet-type, 13, susceptibility to. bruising and prolonged epistaxis since infancy. Laboratory studies showed lack of platelet aggregation in response to low doses of arachidonic acid and impaired aggregation in response to a TBXA2 agonist. Platelets from the father showed a similar pattern, although he had no bleeding symptoms.
Inheritance
Susceptibility to this bleeding disorder due to defective thromboxane A2 receptor is an autosomal dominant trait (Hirata et al., 1994).
Molecular Genetics
In affected members of 2 unrelated families with a bleeding disorder (Ushikubi et al., 1987 and Fuse et al., 1993), Hirata et al. (1994) identified a heterozygous mutation in the TBXA2 gene (R60L; 188070.0001). The mutant receptor expressed in Chinese hamster ovary cells showed normal ligand binding affinities, but decreased agonist-induced second messenger formation. Dominant inheritance of the disorder suggested that the mutation produces a dominant-negative effect. In a | [
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omim | https://www.omim.org/entry/614009 | rD474Pr | BLEEDING DISORDER, PLATELET-TYPE, 13, SUSCEPTIBILITY TO | C3279614 | 13 | bleeding disorder, platelet-type, 13, susceptibility to. 2 unrelated families with a bleeding disorder (Ushikubi et al., 1987 and Fuse et al., 1993), Hirata et al. (1994) identified a heterozygous mutation in the TBXA2 gene (R60L; 188070.0001). The mutant receptor expressed in Chinese hamster ovary cells showed normal ligand binding affinities, but decreased agonist-induced second messenger formation. Dominant inheritance of the disorder suggested that the mutation produces a dominant-negative effect. In a 14-year-old white boy with a mild mucocutaneous bleeding disorder characterized by defective platelet response to TBXA2, Mumford et al. (2010) identified a heterozygous mutation in the TBXA2R gene (D304N; 188070.0002). The patient's father, who also carried the mutation, had no bleeding symptoms. In vitro studies of platelets from both the boy and his | [
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omim | https://www.omim.org/entry/614009 | rD474Pr | BLEEDING DISORDER, PLATELET-TYPE, 13, SUSCEPTIBILITY TO | C3279614 | 13 | bleeding disorder, platelet-type, 13, susceptibility to. disorder suggested that the mutation produces a dominant-negative effect. In a 14-year-old white boy with a mild mucocutaneous bleeding disorder characterized by defective platelet response to TBXA2, Mumford et al. (2010) identified a heterozygous mutation in the TBXA2R gene (D304N; 188070.0002). The patient's father, who also carried the mutation, had no bleeding symptoms. In vitro studies of platelets from both the boy and his father showed impaired aggregation and ATP secretion responses to arachidonic acid and a TBXA2R agonist. In vitro functional expression studies in CHO cells showed normal surface membrane expression of the mutant protein, but there was significantly decreased binding and a significant reduction (more than 85%) in intracellular calcium levels in response to a TBXA2R agonist compared to wildtype, consistent with a loss of function. Noting the phenotypic differences between the boy and his | [
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omim | https://www.omim.org/entry/614009 | rD474Pr | BLEEDING DISORDER, PLATELET-TYPE, 13, SUSCEPTIBILITY TO | C3279614 | 13 | bleeding disorder, platelet-type, 13, susceptibility to. bleeding symptoms. In vitro studies of platelets from both the boy and his father showed impaired aggregation and ATP secretion responses to arachidonic acid and a TBXA2R agonist. In vitro functional expression studies in CHO cells showed normal surface membrane expression of the mutant protein, but there was significantly decreased binding and a significant reduction (more than 85%) in intracellular calcium levels in response to a TBXA2R agonist compared to wildtype, consistent with a loss of function. Noting the phenotypic differences between the boy and his father, Mumford et al. (2010) speculated that the clinical bleeding phenotype demonstrated by the boy represented the effect of the heterozygous D304N mutation combined with an additional unidentified hemostatic defect. Mumford et al. (2010) concluded that heterozygosity for mutations in the TBXA2R gene is sufficient to cause abnormal platelet functional responses in vitro, but is insufficient to cause clinically significant dysfunction in vivo. In an individual whose platelets showed | [
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omim | https://www.omim.org/entry/614009 | rD474Pr | BLEEDING DISORDER, PLATELET-TYPE, 13, SUSCEPTIBILITY TO | C3279614 | 13 | bleeding disorder, platelet-type, 13, susceptibility to. loss of function. Noting the phenotypic differences between the boy and his father, Mumford et al. (2010) speculated that the clinical bleeding phenotype demonstrated by the boy represented the effect of the heterozygous D304N mutation combined with an additional unidentified hemostatic defect. Mumford et al. (2010) concluded that heterozygosity for mutations in the TBXA2R gene is sufficient to cause abnormal platelet functional responses in vitro, but is insufficient to cause clinically significant dysfunction in vivo. In an individual whose platelets showed defective response to TBXA2 in vitro, Flamm et al. (2012) identified a heterozygous mutation in the TBXA2R gene (V241G; 188070.0003). In vitro functional expression studies showed normal expression of the mutant receptor, but impaired calcium mobilization and aggregation in response to a TBXA2 agonist. Because G protein signaling through ADP was normal, Flamm et al. (2012) concluded that | [
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omim | https://www.omim.org/entry/614009 | rD474Pr | BLEEDING DISORDER, PLATELET-TYPE, 13, SUSCEPTIBILITY TO | C3279614 | 13 | bleeding disorder, platelet-type, 13, susceptibility to. to cause clinically significant dysfunction in vivo. In an individual whose platelets showed defective response to TBXA2 in vitro, Flamm et al. (2012) identified a heterozygous mutation in the TBXA2R gene (V241G; 188070.0003). In vitro functional expression studies showed normal expression of the mutant receptor, but impaired calcium mobilization and aggregation in response to a TBXA2 agonist. Because G protein signaling through ADP was normal, Flamm et al. (2012) concluded that the mutation caused abnormal coupling of TBXA2R to Gq, resulting in impaired calcium mobilization. The individual's platelets also showed impaired response to the anticoagulants aspirin and indomethacin, which inhibit the production of thromboxane A2. The individual had no self-reported bleeding tendencies.
INHERITANCE
- Autosomal dominant
HEAD & NECK
Nose
- Epistaxis
SKIN, NAILS, & HAIR
Skin
- Ecchymoses
- Easy bruising
HEMATOLOGY
- Bleeding tendency, | [
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] |
omim | https://www.omim.org/entry/614009 | rD474Pr | BLEEDING DISORDER, PLATELET-TYPE, 13, SUSCEPTIBILITY TO | C3279614 | 13 | bleeding disorder, platelet-type, 13, susceptibility to. ADP was normal, Flamm et al. (2012) concluded that the mutation caused abnormal coupling of TBXA2R to Gq, resulting in impaired calcium mobilization. The individual's platelets also showed impaired response to the anticoagulants aspirin and indomethacin, which inhibit the production of thromboxane A2. The individual had no self-reported bleeding tendencies.
INHERITANCE
- Autosomal dominant
HEAD & NECK
Nose
- Epistaxis
SKIN, NAILS, & HAIR
Skin
- Ecchymoses
- Easy bruising
HEMATOLOGY
- Bleeding tendency, mild
- Defective platelet aggregation in response to arachidonic acid
- Defective platelet calcium mobilization
- Normal platelet count
- Normal serum thromboxane B2
MOLECULAR BASIS
- Susceptibility conferred by mutation in the platelet thromboxane A2 receptor gene (TBXA2R,
188070.0001
)
▲ Close | [
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] |
omim | https://www.omim.org/entry/614009 | rD474Pr | BLEEDING DISORDER, PLATELET-TYPE, 13, SUSCEPTIBILITY TO | C3279614 | 13 | bleeding disorder, platelet-type, 13, susceptibility to. hymoses
- Easy bruising
HEMATOLOGY
- Bleeding tendency, mild
- Defective platelet aggregation in response to arachidonic acid
- Defective platelet calcium mobilization
- Normal platelet count
- Normal serum thromboxane B2
MOLECULAR BASIS
- Susceptibility conferred by mutation in the platelet thromboxane A2 receptor gene (TBXA2R,
188070.0001
)
▲ Close | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. SummaryClinical characteristics.Trichohepatoenteric syndrome (THES), generally considered to be a neonatal enteropathy, is characterized by intractable diarrhea (seen in almost all affected children), woolly hair (seen in all), intrauterine growth restriction, facial dysmorphism, and short stature. Additional findings include poorly characterized immunodeficiency, recurrent infections, skin abnormalities, and liver disease. Mild intellectual disability (ID) is seen in about 50% of affected individuals. Less common findings include congenital heart defects and platelet anomalies. To date 52 affected individuals have been reported.Diagnosis/testing.The diagnosis of THES is established in a proband with biallelic pathogenic variants in either TTC37 or SKIV2L.Management.Treatment of manifestations: To promote maximal weight gain and linear growth, most children initially require parenteral nutrition (PN). As tolerated, oral feeding (typically a semi-elemental diet) can be combined with PN. On the rare occasion that | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. Less common findings include congenital heart defects and platelet anomalies. To date 52 affected individuals have been reported.Diagnosis/testing.The diagnosis of THES is established in a proband with biallelic pathogenic variants in either TTC37 or SKIV2L.Management.Treatment of manifestations: To promote maximal weight gain and linear growth, most children initially require parenteral nutrition (PN). As tolerated, oral feeding (typically a semi-elemental diet) can be combined with PN. On the rare occasion that PN is unnecessary, anecdotal reports describe use of mainly an amino acid-based formula. To reduce the burden of infections, immunoglobulins can be supplemented in those with low immunoglobulin levels or immunoglobulin functional abnormalities. Patient-specific management of ID is based on age-appropriate assessments of cognitive development, speech and language development, and psychosocial skills.Surveillance: For children not receiving PN: close monitoring of nutritional status by a pediatric nutritionist to assure prompt intervention as needed. Yearly | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. with PN. On the rare occasion that PN is unnecessary, anecdotal reports describe use of mainly an amino acid-based formula. To reduce the burden of infections, immunoglobulins can be supplemented in those with low immunoglobulin levels or immunoglobulin functional abnormalities. Patient-specific management of ID is based on age-appropriate assessments of cognitive development, speech and language development, and psychosocial skills.Surveillance: For children not receiving PN: close monitoring of nutritional status by a pediatric nutritionist to assure prompt intervention as needed. Yearly assessment of: diarrhea for changes that could suggest inflammatory bowel disease; liver function and size; immunoglobulin serum concentration and functionality; TSH level for evidence of hypothyroidism. Periodic assessment of: cognitive development, speech and language, and psychosocial skills for evidence of ID.Genetic counseling.THES 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 | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. to assure prompt intervention as needed. Yearly assessment of: diarrhea for changes that could suggest inflammatory bowel disease; liver function and size; immunoglobulin serum concentration and functionality; TSH level for evidence of hypothyroidism. Periodic assessment of: cognitive development, speech and language, and psychosocial skills for evidence of ID.Genetic counseling.THES 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. Once the SKIV2L or TTC37 pathogenic variants have been identified in an affected family member, carrier testing of at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible.DiagnosisTo date, no diagnostic algorithm for trichohepatoenteric syndrome (THES) has been published.Suggestive FindingsTHES should be suspected in individuals with the following clinical findings | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the SKIV2L or TTC37 pathogenic variants have been identified in an affected family member, carrier testing of at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing are possible.DiagnosisTo date, no diagnostic algorithm for trichohepatoenteric syndrome (THES) has been published.Suggestive FindingsTHES should be suspected in individuals with the following clinical findings :Growth failure. * Intrauterine growth restriction (IUGR) / small for gestational age (SGA), short statureIntractable/chronic diarrhea * beginning in infancy that persists despite bowel rest or, on rare occasion, shows very early-onset inflammatory bowel disease (VEOIBD) of infancy. Endoscopic evaluation is often normal, but can resemble IBD. Intestinal biopsy findings range from mild villous atrophy to severe villous atrophy .Woolly, brittle, easily break | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. suspected in individuals with the following clinical findings :Growth failure. * Intrauterine growth restriction (IUGR) / small for gestational age (SGA), short statureIntractable/chronic diarrhea * beginning in infancy that persists despite bowel rest or, on rare occasion, shows very early-onset inflammatory bowel disease (VEOIBD) of infancy. Endoscopic evaluation is often normal, but can resemble IBD. Intestinal biopsy findings range from mild villous atrophy to severe villous atrophy .Woolly, brittle, easily breakable hair. Hair analysis using light microscopy showed trichorrhexis nodosa in 42/52 individuals .Immunodeficiency that is poorly characterized, but typically low immunoglobulin levels and/or poor antibody production after immunization. Monoclonal hyper-IgA has been described .Liver disease, mostly hepatomegaly and/or elevated liver enzymes; fibrosis or cirrhosis can occur. Hemochromatosis has been described, particularly when liver findings are significant .Café au lait spots or dyschromic | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. Woolly, brittle, easily breakable hair. Hair analysis using light microscopy showed trichorrhexis nodosa in 42/52 individuals .Immunodeficiency that is poorly characterized, but typically low immunoglobulin levels and/or poor antibody production after immunization. Monoclonal hyper-IgA has been described .Liver disease, mostly hepatomegaly and/or elevated liver enzymes; fibrosis or cirrhosis can occur. Hemochromatosis has been described, particularly when liver findings are significant .Café au lait spots or dyschromic spots have been described in nearly half of individuals reported . Of note, a subset of affected individuals from the Arabian peninsula have pelvic, girdle, and lower-limb skin hyperpigmentation .* The association of neonatal intractable diarrhea and IUGR suggests the diagnosis of THES.Establishing the DiagnosisThe diagnosis of THES is established in a proband with biallelic pathogenic variants in TTC37 or SKIV2L (Table 1).Molecular genetic testing approaches | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. au lait spots or dyschromic spots have been described in nearly half of individuals reported . Of note, a subset of affected individuals from the Arabian peninsula have pelvic, girdle, and lower-limb skin hyperpigmentation .* The association of neonatal intractable diarrhea and IUGR suggests the diagnosis of THES.Establishing the DiagnosisThe diagnosis of THES is established in a proband with biallelic pathogenic variants in TTC37 or SKIV2L (Table 1).Molecular genetic testing approaches can include a combination of gene-targeted testing (serial single-gene testing or a multigene panel) and comprehensive
genomic testing depending on the phenotype.Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of THES is broad, children with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with a | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. Table 1).Molecular genetic testing approaches can include a combination of gene-targeted testing (serial single-gene testing or a multigene panel) and comprehensive
genomic testing depending on the phenotype.Gene-targeted testing requires that the clinician determine which gene(s) are likely involved, whereas genomic testing does not. Because the phenotype of THES is broad, children with the distinctive findings described in Suggestive Findings are likely to be diagnosed using gene-targeted testing (see Option 1), whereas those with a phenotype indistinguishable from many other inherited disorders with diarrhea, liver disease, and immunodeficiency will be more likely to be diagnosed using genomic testing (see Option 2).Option 1When the phenotypic and laboratory findings suggest the diagnosis of THES, molecular genetic testing approaches can include serial single-gene testing or use of a multigene panel.Serial single-gene testing. Sequence analysis of TTC37 is performed first and – if no pathogenic variants are identified – followed by | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. Option 1), whereas those with a phenotype indistinguishable from many other inherited disorders with diarrhea, liver disease, and immunodeficiency will be more likely to be diagnosed using genomic testing (see Option 2).Option 1When the phenotypic and laboratory findings suggest the diagnosis of THES, molecular genetic testing approaches can include serial single-gene testing or use of a multigene panel.Serial single-gene testing. Sequence analysis of TTC37 is performed first and – if no pathogenic variants are identified – followed by sequence analysis of SKIV2L. If only one pathogenic variant is found, gene-targeted deletion/duplication analysis could be considered; however, to date no exon or whole-gene deletions or duplications have been reported in either gene.A multigene very early-onset IBD (VEOIBD) panel that includes SKIV2L and TTC37 and other genes of interest (see Differential Diagnosis) typically provides the best opportunity to identify the genetic cause of | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. no pathogenic variants are identified – followed by sequence analysis of SKIV2L. If only one pathogenic variant is found, gene-targeted deletion/duplication analysis could be considered; however, to date no exon or whole-gene deletions or duplications have been reported in either gene.A multigene very early-onset IBD (VEOIBD) panel that includes SKIV2L and TTC37 and other genes of interest (see Differential Diagnosis) typically provides the best opportunity to identify the genetic cause of the condition at the most reasonable cost while limiting identification of 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; conversely, given the rarity of THES, some panels for diarrhea | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. best opportunity to identify the genetic cause of the condition at the most reasonable cost while limiting identification of 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; conversely, given the rarity of THES, some panels for diarrhea, hepatic disease, and immunodeficiency may not include these genes. (3) 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 2When the phenotype is indistinguishable from many other inherited disorders with diarrhea, hepatic disease, and immunodeficiency, comprehensive
genomic testing (which does | [
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] |
gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. of THES, some panels for diarrhea, hepatic disease, and immunodeficiency may not include these genes. (3) 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 2When the phenotype is indistinguishable from many other inherited disorders with diarrhea, hepatic disease, and immunodeficiency, comprehensive
genomic testing (which does not require the clinician to determine which gene are likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible, although not yet easily analyzed in a clinical setting.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 Trichohepatoenteric SyndromeView in own windowGene 1Proportion of THESAttributed to Pathogenic | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. immunodeficiency, comprehensive
genomic testing (which does not require the clinician to determine which gene are likely involved) is the best option. Exome sequencing is most commonly used; genome sequencing is also possible, although not yet easily analyzed in a clinical setting.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 Trichohepatoenteric SyndromeView in own windowGene 1Proportion of THESAttributed to PathogenicVariants in GeneProportion of Pathogenic Variants 2 Detectable by MethodSequenceanalysis 3Gene-targeted deletion/duplication analysis 4SKIV2L16/52 5(31%)All variants reported to dateUnknown, none reported to dateTTC3736/52 6(69%)All variants reported to dateUnknown, none reported to date1. See Table A. Genes and Databases for chromosome locus and protein.2 | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. THESAttributed to PathogenicVariants in GeneProportion of Pathogenic Variants 2 Detectable by MethodSequenceanalysis 3Gene-targeted deletion/duplication analysis 4SKIV2L16/52 5(31%)All variants reported to dateUnknown, none reported to dateTTC3736/52 6(69%)All variants reported to dateUnknown, none reported to date1. 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. Gene-targeted deletion/duplication | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. 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. 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. n=6: Fabre et al ; n=4: Monies et al (patients #1, 2, 3, 5); n=2: Lee et al (patients LL, LF) | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. 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. n=6: Fabre et al ; n=4: Monies et al (patients #1, 2, 3, 5); n=2: Lee et al (patients LL, LF); n=1: Morgan et al , Kammermeier et al , Zheng et al , Kammermeier et al 6. n=12: Hartley et al ; n=9: Fabre et al ; n=2: Kotecha et al , Chong et al , Lee et al , Kinnear et al ; n=1: Bozzetti et al , Kammermeier | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. et al (patients LL, LF); n=1: Morgan et al , Kammermeier et al , Zheng et al , Kammermeier et al 6. n=12: Hartley et al ; n=9: Fabre et al ; n=2: Kotecha et al , Chong et al , Lee et al , Kinnear et al ; n=1: Bozzetti et al , Kammermeier et al , Monies et al (patient #4), Oz-Levi et al , Rider et al , Lee et al (patient CHT), Kammermeier et al Clinical CharacteristicsClinical DescriptionTrichohepatoenteric syndrome (THES) is considered a syndrome of neonatal enteropathy . THES is characterized by the association of intractable diarrhea (seen in almost all affected children), woolly hair (seen in all, | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. et al , Kammermeier et al , Monies et al (patient #4), Oz-Levi et al , Rider et al , Lee et al (patient CHT), Kammermeier et al Clinical CharacteristicsClinical DescriptionTrichohepatoenteric syndrome (THES) is considered a syndrome of neonatal enteropathy . THES is characterized by the association of intractable diarrhea (seen in almost all affected children), woolly hair (seen in all, but may not be obvious at a young age or due to cultural grooming practices), intrauterine growth restriction (IUGR), facial dysmorphism, and short stature, as well as poorly characterized immunodeficiency (sometimes with macrophage activation syndrome), recurrent infections, skin abnormalities, and liver disease. Intellectual disability (ID) is seen in about 50% of children. Less common findings include congenital heart defects and platelet anomalies. To date 52 affected individuals have been reported (see | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. woolly hair (seen in all, but may not be obvious at a young age or due to cultural grooming practices), intrauterine growth restriction (IUGR), facial dysmorphism, and short stature, as well as poorly characterized immunodeficiency (sometimes with macrophage activation syndrome), recurrent infections, skin abnormalities, and liver disease. Intellectual disability (ID) is seen in about 50% of children. Less common findings include congenital heart defects and platelet anomalies. To date 52 affected individuals have been reported (see Table 1).Intractable diarrhea usually begins in the first days of life but sometimes can be delayed until later in the first year of life. The diarrhea persists despite bowel rest (i.e., use of parenteral nutrition). Stools are watery; in rare cases blood can be found. The diarrhea leads to malabsorption and failure to thrive, which typically requires parenteral nutrition (see Management). To date, the diarrhea has appeared to be lifelong .Very | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. 52 affected individuals have been reported (see Table 1).Intractable diarrhea usually begins in the first days of life but sometimes can be delayed until later in the first year of life. The diarrhea persists despite bowel rest (i.e., use of parenteral nutrition). Stools are watery; in rare cases blood can be found. The diarrhea leads to malabsorption and failure to thrive, which typically requires parenteral nutrition (see Management). To date, the diarrhea has appeared to be lifelong .Very rarely, the clinical presentation can resemble so-called very early-onset inflammatory bowel disease (VEOIBD).In the only instance in which immunodeficiency was reported to be the major clinical finding, the child never manifested the characteristic diarrhea .Woolly, brittle hair. Detailed clinical descriptions of the hair provided for 41 individuals included the following: woolly (n=22), poorly pigmented / light (n=18), easily removable / brittle ( | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. diarrhea has appeared to be lifelong .Very rarely, the clinical presentation can resemble so-called very early-onset inflammatory bowel disease (VEOIBD).In the only instance in which immunodeficiency was reported to be the major clinical finding, the child never manifested the characteristic diarrhea .Woolly, brittle hair. Detailed clinical descriptions of the hair provided for 41 individuals included the following: woolly (n=22), poorly pigmented / light (n=18), easily removable / brittle (n=19), and unmanageable / unable to be combed (n=15) (e.g., Bozzetti et al , Busoni et al ).Growth failureIntrauterine growth restriction (IUGR) / small for gestational age (SGA). Most children are below the 10th centile at birth either for height or for weight .Short stature. Despite adequate nutrition, the last recorded height in more than 50% | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. ), easily removable / brittle (n=19), and unmanageable / unable to be combed (n=15) (e.g., Bozzetti et al , Busoni et al ).Growth failureIntrauterine growth restriction (IUGR) / small for gestational age (SGA). Most children are below the 10th centile at birth either for height or for weight .Short stature. Despite adequate nutrition, the last recorded height in more than 50% of affected individuals was below the 3rd centile .Although to date no adult with THES has been described in detail, the heights in the three older individuals for whom that information was available were the following:148 cm (-2.36 SD) in a woman age 27 years 171 cm (-0.74 SD) in a man age 18 years -5 SD in a woman age 17 years Immunodeficiency. Children are prone to recurrent infection . Both viral infections | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. last recorded height in more than 50% of affected individuals was below the 3rd centile .Although to date no adult with THES has been described in detail, the heights in the three older individuals for whom that information was available were the following:148 cm (-2.36 SD) in a woman age 27 years 171 cm (-0.74 SD) in a man age 18 years -5 SD in a woman age 17 years Immunodeficiency. Children are prone to recurrent infection . Both viral infections (respiratory syncytial virus , Epstein Barr virus ) and bacterial infections have been reported.Nine of 15 individuals with THES had a transient hemophagocytic syndrome / macrophage activation syndrome ; however, no specific data were provided about diagnosis or management.Infection was implicated in the death of seven of 21 patients.Liver disease, found in about half of patients, is mostly cirrhosis and fibrosis . In seven of 17 individuals for whom the cause of death was described, liver disease ( | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. prone to recurrent infection . Both viral infections (respiratory syncytial virus , Epstein Barr virus ) and bacterial infections have been reported.Nine of 15 individuals with THES had a transient hemophagocytic syndrome / macrophage activation syndrome ; however, no specific data were provided about diagnosis or management.Infection was implicated in the death of seven of 21 patients.Liver disease, found in about half of patients, is mostly cirrhosis and fibrosis . In seven of 17 individuals for whom the cause of death was described, liver disease (mostly liver failure or cirrhosis) was implicated . One patient developed a hepatoblastoma .Pathology showed iron overload and sometimes hemochromatosis . In some instances, hemochromatosis improved with time .Mild intellectual disability, described in about half of patients , is poorly characterized.Brain MRI – when performed – appears normal .Skin abnormalities. The most common are café au lait spots that preferentially appear on the lower limbs . Later in life, xerosis and/or rubber | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. of death was described, liver disease (mostly liver failure or cirrhosis) was implicated . One patient developed a hepatoblastoma .Pathology showed iron overload and sometimes hemochromatosis . In some instances, hemochromatosis improved with time .Mild intellectual disability, described in about half of patients , is poorly characterized.Brain MRI – when performed – appears normal .Skin abnormalities. The most common are café au lait spots that preferentially appear on the lower limbs . Later in life, xerosis and/or rubbery skin can be observed.Congenital cardiac defects, which are seldom seen, vary. The following were observed among 12 patients with cardiac or aortic defects: ventricular septal defect (n=2) ; atrial septal defect (n=2) ; tetralogy of Fallot (n=1) . Others had a bicuspid aortic valve with or without other anomalies, an aortic defect, or a mildly dilated aortic sinus.Platelets can be enlarged with no known functional | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. life, xerosis and/or rubbery skin can be observed.Congenital cardiac defects, which are seldom seen, vary. The following were observed among 12 patients with cardiac or aortic defects: ventricular septal defect (n=2) ; atrial septal defect (n=2) ; tetralogy of Fallot (n=1) . Others had a bicuspid aortic valve with or without other anomalies, an aortic defect, or a mildly dilated aortic sinus.Platelets can be enlarged with no known functional defect .Facial dysmorphism that is mild and nonspecific is observed in nearly all affected individuals. The main findings (coarse features, a wide forehead, broad nasal root, and hypertelorism) can become more apparent with time .Findings observed in a few affected individuals that could be part of the phenotypic spectrum of THES or unrelated findings include the following:Hypothyroidism. n=3/15 affected individuals Dental abnormalities:Peg teeth. n=2 Narrow pointed teeth | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. Platelets can be enlarged with no known functional defect .Facial dysmorphism that is mild and nonspecific is observed in nearly all affected individuals. The main findings (coarse features, a wide forehead, broad nasal root, and hypertelorism) can become more apparent with time .Findings observed in a few affected individuals that could be part of the phenotypic spectrum of THES or unrelated findings include the following:Hypothyroidism. n=3/15 affected individuals Dental abnormalities:Peg teeth. n=2 Narrow pointed teeth and dental dysplasia. n=2 Inguinal hernia. n=2 One individual each:Small kidneys Perthe syndrome Glaucoma Polycystic kidney Thymus atrophy (in an individual without a molecular diagnosis) Phenotype Correlations by GeneCurrent data suggest that individuals with biallelic pathogenic variants in either SKIV2L or TTC37 are indistinguishable clinically.Genotype-Phenotype CorrelationsBecause most pathogenic variants are private, genotype/phenotype correlations are difficult.Of note, the phenotypes | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. teeth. n=2 Narrow pointed teeth and dental dysplasia. n=2 Inguinal hernia. n=2 One individual each:Small kidneys Perthe syndrome Glaucoma Polycystic kidney Thymus atrophy (in an individual without a molecular diagnosis) Phenotype Correlations by GeneCurrent data suggest that individuals with biallelic pathogenic variants in either SKIV2L or TTC37 are indistinguishable clinically.Genotype-Phenotype CorrelationsBecause most pathogenic variants are private, genotype/phenotype correlations are difficult.Of note, the phenotypes were indistinguishable in the five individuals with the recurrent TTC37 variant (Trp936Ter) and those with other TTC37 pathogenic variants .PrevalenceTHES is rare. To date about 50 affected individuals have been reported.The best estimate of prevalence is 1:1,000,000 births, based on the French cohort of Fabre & Badens .Affected individuals have been reported worldwide.As with all autosomal recessive disorders, the prevalence may be | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. are difficult.Of note, the phenotypes were indistinguishable in the five individuals with the recurrent TTC37 variant (Trp936Ter) and those with other TTC37 pathogenic variants .PrevalenceTHES is rare. To date about 50 affected individuals have been reported.The best estimate of prevalence is 1:1,000,000 births, based on the French cohort of Fabre & Badens .Affected individuals have been reported worldwide.As with all autosomal recessive disorders, the prevalence may be increased in highly consanguineous populations.Differential DiagnosisTable 3. Monogenic Disorders with Intractable Diarrhea to Consider in the Differential Diagnosis of Trichohepatoenteric SyndromeView in own windowDisorderGeneMOIDistinguishing Clinical Features of Differential Diagnosis DisorderCongenital tufting enteropathy(OMIM 613217)EPCAMARSpecific intestinal pathology (tuft)IPEX syndromeFOXP3XLLow regulatory T cellsGastrointestinal defects and | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. autosomal recessive disorders, the prevalence may be increased in highly consanguineous populations.Differential DiagnosisTable 3. Monogenic Disorders with Intractable Diarrhea to Consider in the Differential Diagnosis of Trichohepatoenteric SyndromeView in own windowDisorderGeneMOIDistinguishing Clinical Features of Differential Diagnosis DisorderCongenital tufting enteropathy(OMIM 613217)EPCAMARSpecific intestinal pathology (tuft)IPEX syndromeFOXP3XLLow regulatory T cellsGastrointestinal defects and immunodeficiency syndrome (OMIM 243150)TTC7AARDuodenal atresiaSyndromic congenital tufting enteropathy (OMIM 270420)SPINT2ARSpecific intestinal pathology (tuft)Choanal atresiaAR = autosomal recessive; IPEX = immune dysregulation, polyendocrinopathy, enteropathy, X-linked; MOI = mode of inheritance; XL = X-linkedSee Diarrhea, congenital: OMIM Phenotypic | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. T cellsGastrointestinal defects and immunodeficiency syndrome (OMIM 243150)TTC7AARDuodenal atresiaSyndromic congenital tufting enteropathy (OMIM 270420)SPINT2ARSpecific intestinal pathology (tuft)Choanal atresiaAR = autosomal recessive; IPEX = immune dysregulation, polyendocrinopathy, enteropathy, X-linked; MOI = mode of inheritance; XL = X-linkedSee Diarrhea, congenital: OMIM Phenotypic Series to view genes associated with this phenotype in OMIM.ManagementEvaluations Following Initial DiagnosisTo establish the extent of disease and needs in an individual diagnosed with trichohepatoenteric syndrome (THES), the following evaluations are recommended:Nutritional evaluation by a specialist pediatric nutritionistImmunologic assessment with serum IgG, IgM, IgA; immunophenotyping; if immunization has been performed before, evaluation of the level of specific antibodies to detect a rapid loss of protective antibodies, | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. e Diarrhea, congenital: OMIM Phenotypic Series to view genes associated with this phenotype in OMIM.ManagementEvaluations Following Initial DiagnosisTo establish the extent of disease and needs in an individual diagnosed with trichohepatoenteric syndrome (THES), the following evaluations are recommended:Nutritional evaluation by a specialist pediatric nutritionistImmunologic assessment with serum IgG, IgM, IgA; immunophenotyping; if immunization has been performed before, evaluation of the level of specific antibodies to detect a rapid loss of protective antibodies, which would require immunoglobulin supplementationLiver assessment: ultrasound evaluation; assessment of liver enzymes (ALT/AST, GGT); in case of abnormalities, consult a pediatric hepatologist for recommendations on additional investigationsCardiac evaluation for congenital malformationsAge-appropriate assessment of cognitive development, speech and language development, and psychosocial skillsConsultation with a clinical geneticist and/or genetic counselorTreatment of ManifestationsNo specific treatment is available. The goals of the treatment are | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. detect a rapid loss of protective antibodies, which would require immunoglobulin supplementationLiver assessment: ultrasound evaluation; assessment of liver enzymes (ALT/AST, GGT); in case of abnormalities, consult a pediatric hepatologist for recommendations on additional investigationsCardiac evaluation for congenital malformationsAge-appropriate assessment of cognitive development, speech and language development, and psychosocial skillsConsultation with a clinical geneticist and/or genetic counselorTreatment of ManifestationsNo specific treatment is available. The goals of the treatment are to promote maximal weight gain and linear growth, to reduce the burden of infections, and to provide patient-specific management of intellectual disability.Weight gain. Most children, when first diagnosed, require parenteral nutrition (PN) to achieve appropriate weight gain and catch-up growth. Although PN is usually required, it can be combined (as tolerated) with oral feeding – typically a semi-elemental diet . About 30%-50% of patients can become independent of parenteral | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. available. The goals of the treatment are to promote maximal weight gain and linear growth, to reduce the burden of infections, and to provide patient-specific management of intellectual disability.Weight gain. Most children, when first diagnosed, require parenteral nutrition (PN) to achieve appropriate weight gain and catch-up growth. Although PN is usually required, it can be combined (as tolerated) with oral feeding – typically a semi-elemental diet . About 30%-50% of patients can become independent of parenteral nutrition after prolonged PN. Of note, promotion of oral feeding as tolerated (rather than enteral tube feeding) should help prevent future eating disorders.To date nine individuals have been reported in whom PN was unnecessary . In three of the nine, the diet was an amino acid formula ; it is not clear if weight gain was adequate, or if catch-up growth was achieved.When early-onset manifestations are those of inflammatory bowel disease (IBD), infections should be | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. % of patients can become independent of parenteral nutrition after prolonged PN. Of note, promotion of oral feeding as tolerated (rather than enteral tube feeding) should help prevent future eating disorders.To date nine individuals have been reported in whom PN was unnecessary . In three of the nine, the diet was an amino acid formula ; it is not clear if weight gain was adequate, or if catch-up growth was achieved.When early-onset manifestations are those of inflammatory bowel disease (IBD), infections should be ruled out and routine management of IBD with steroids, azathioprine, and anti-TNF (tumor necrosis factor) antibody can be considered; however, this routine IBD management may result in only transient improvement, or no improvement .Growth. Anecdotal experience shows no efficacy of growth hormone treatment .Infection. Immunoglobulin supplementation for those with low immunoglobulin levels appears to lower the rate of infection .Of note, hematopoietic stem cell transplantation (HSCT) – reported twice to date – has been | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. disease (IBD), infections should be ruled out and routine management of IBD with steroids, azathioprine, and anti-TNF (tumor necrosis factor) antibody can be considered; however, this routine IBD management may result in only transient improvement, or no improvement .Growth. Anecdotal experience shows no efficacy of growth hormone treatment .Infection. Immunoglobulin supplementation for those with low immunoglobulin levels appears to lower the rate of infection .Of note, hematopoietic stem cell transplantation (HSCT) – reported twice to date – has been unsuccessful: one patient succumbed to infection and the other showed only mild improvement .Intellectual disability is managed specifically according to the results of age-appropriate assessments of cognitive development, speech and language development, and psychosocial skills.Tooth shape abnormalities. Evaluation of abnormal dentition in children is especially important because teeth are required for development of speech, nutrition, self-esteem, and well-being. The National Foundation for Ectodermal Dysplasias (NFED) website provides | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. – reported twice to date – has been unsuccessful: one patient succumbed to infection and the other showed only mild improvement .Intellectual disability is managed specifically according to the results of age-appropriate assessments of cognitive development, speech and language development, and psychosocial skills.Tooth shape abnormalities. Evaluation of abnormal dentition in children is especially important because teeth are required for development of speech, nutrition, self-esteem, and well-being. The National Foundation for Ectodermal Dysplasias (NFED) website provides further resources and information.Hair changes. Fragile hair and hair loss can have a deeper-than-expected emotional impact on a patient and family. Counseling may be helpful. Also, hair prosthetics (wigs) are available through Locks of Love and other organizations; some insurance provides two wigs per year in growing children with alopecia. A prescription for a cranial prosthesis may or may not aid insurance reimbursement.SurveillanceAlthough there are no consensus guidelines | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. Dysplasias (NFED) website provides further resources and information.Hair changes. Fragile hair and hair loss can have a deeper-than-expected emotional impact on a patient and family. Counseling may be helpful. Also, hair prosthetics (wigs) are available through Locks of Love and other organizations; some insurance provides two wigs per year in growing children with alopecia. A prescription for a cranial prosthesis may or may not aid insurance reimbursement.SurveillanceAlthough there are no consensus guidelines, the following surveillance is recommended:For children not receiving parenteral nutrition, close monitoring of nutritional status by a pediatric nutritionist to assure prompt intervention should nutritional deficiency become a concernYearly assessment of the following main features:Diarrhea. If the nature of the diarrhea changes (e.g., appearance of bloody diarrhea), investigation of possible inflammatory bowel disease (IBD) is warranted .Liver function. Ultrasound examination and measurement of liver enzymes (AST, ALT | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. Although there are no consensus guidelines, the following surveillance is recommended:For children not receiving parenteral nutrition, close monitoring of nutritional status by a pediatric nutritionist to assure prompt intervention should nutritional deficiency become a concernYearly assessment of the following main features:Diarrhea. If the nature of the diarrhea changes (e.g., appearance of bloody diarrhea), investigation of possible inflammatory bowel disease (IBD) is warranted .Liver function. Ultrasound examination and measurement of liver enzymes (AST, ALT, GGT), International Normalized Ratio (INR), and bilirubinSerum concentration of IgG, IgM, IgA, and immunoglobulin functionality (i.e., immunophenotyping) even if results at the time of initial evaluation were normal. Consultation with an immunologist is warranted if immunoglobulin levels are low or if normal immunoglobulin levels are associated with a loss of specific protective antibody.TSH level for evidence of hypothyroidismAssessment of cognitive development, speech and language, | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. measurement of liver enzymes (AST, ALT, GGT), International Normalized Ratio (INR), and bilirubinSerum concentration of IgG, IgM, IgA, and immunoglobulin functionality (i.e., immunophenotyping) even if results at the time of initial evaluation were normal. Consultation with an immunologist is warranted if immunoglobulin levels are low or if normal immunoglobulin levels are associated with a loss of specific protective antibody.TSH level for evidence of hypothyroidismAssessment of cognitive development, speech and language, and psychosocial skills for evidence of intellectual disability at ages 2, 4, 8, 12, and 15 years unless concerns appear earlierAs evolution of the dermatologic features (mostly hypo- or hyperpigmented patches and hair abnormalities) is unknown, regular evaluation by a dermatologist seems reasonable.Evaluation of Relatives at RiskSee Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.Therapies Under InvestigationSearch ClinicalTrials.gov in the US and EU Clinical | [
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gene_reviews | https://www.ncbi.nlm.nih.gov/books/NBK475802/ | roVQQEk | Trichohepatoenteric Syndrome | C1857276 | 14 | trichohepatoenteric syndrome. of cognitive development, speech and language, and psychosocial skills for evidence of intellectual disability at ages 2, 4, 8, 12, and 15 years unless concerns appear earlierAs evolution of the dermatologic features (mostly hypo- or hyperpigmented patches and hair abnormalities) is unknown, regular evaluation by a dermatologist seems reasonable.Evaluation of Relatives at RiskSee Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.Therapies Under InvestigationSearch 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. | [
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wikipedia | https://en.wikipedia.org/wiki/Tricho-hepato-enteric_syndrome | 6Dm1ALx | Tricho-hepato-enteric syndrome | C1857276 | 15 | tricho-hepato-enteric syndrome. Tricho-hepato-enteric syndromeOther namesIntractable diarrhea of infancy with facial dysmorphismTypical facial abnormalities with prominent forehead and cheeks, broad nasal root and wide-spaced eyes. Abnormal hairs are woolly, easily removed and poorly pigmented.
Tricho-hepato-enteric syndrome (THE), also known as syndromic or phenotypic diarrhea, is an extremely rare congenital bowel disorder which manifests itself as intractable diarrhea in infants with intrauterine growth retardation, hair and facial abnormalities. Many also have liver disease and abnormalities of the immune system. The associated malabsorption leads to malnutrition and failure to thrive.
It is thought to be a genetic disorder with an autosomal recessive inheritance pattern, although responsible genes have not been found and the exact cause remains unknown. Prognosis is poor; many patients die before the age of 5 (mainly from infections or cirrhosis), although most patients nowadays survive with intravenous feeding (parenteral nutrition).
Contents
1 Symptoms
2 | [
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wikipedia | https://en.wikipedia.org/wiki/Tricho-hepato-enteric_syndrome | 6Dm1ALx | Tricho-hepato-enteric syndrome | C1857276 | 15 | tricho-hepato-enteric syndrome. with intrauterine growth retardation, hair and facial abnormalities. Many also have liver disease and abnormalities of the immune system. The associated malabsorption leads to malnutrition and failure to thrive.
It is thought to be a genetic disorder with an autosomal recessive inheritance pattern, although responsible genes have not been found and the exact cause remains unknown. Prognosis is poor; many patients die before the age of 5 (mainly from infections or cirrhosis), although most patients nowadays survive with intravenous feeding (parenteral nutrition).
Contents
1 Symptoms
2 Genetics
3 Diagnosis
3.1 Facial features
3.2 Liver
3.3 Small bowel
3.4 Hair
3.5 Platelets
3.6 Other
4 Treatment
5 Epidemiology
6 Footnotes
7 References
8 External links
Symptoms
Tricho-hepato-enteric syndrome is one particular form of intractable diarrhea of infancy, presenting typically in the first month of life. These babies were usually born small for their age and continue to experience failure to thrive, usually | [
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wikipedia | https://en.wikipedia.org/wiki/Tricho-hepato-enteric_syndrome | 6Dm1ALx | Tricho-hepato-enteric syndrome | C1857276 | 15 | tricho-hepato-enteric syndrome. intravenous feeding (parenteral nutrition).
Contents
1 Symptoms
2 Genetics
3 Diagnosis
3.1 Facial features
3.2 Liver
3.3 Small bowel
3.4 Hair
3.5 Platelets
3.6 Other
4 Treatment
5 Epidemiology
6 Footnotes
7 References
8 External links
Symptoms
Tricho-hepato-enteric syndrome is one particular form of intractable diarrhea of infancy, presenting typically in the first month of life. These babies were usually born small for their age and continue to experience failure to thrive, usually with a final short stature. Typical facial features include prominent forehead and cheeks, a broad nasal root and widely spaced eyes (hypertelorism). Their hairs are woolly, easily removed and poorly pigmented. Liver disease is mainly present as cirrhosis or fibrosis, and staining might reveal high iron content of the liver cells (consistent with hemochromatosis). Most evaluated patients had some degree of decrease in intelligence.
Genetics
The syndrome appears to be | [
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wikipedia | https://en.wikipedia.org/wiki/Tricho-hepato-enteric_syndrome | 6Dm1ALx | Tricho-hepato-enteric syndrome | C1857276 | 15 | tricho-hepato-enteric syndrome. age and continue to experience failure to thrive, usually with a final short stature. Typical facial features include prominent forehead and cheeks, a broad nasal root and widely spaced eyes (hypertelorism). Their hairs are woolly, easily removed and poorly pigmented. Liver disease is mainly present as cirrhosis or fibrosis, and staining might reveal high iron content of the liver cells (consistent with hemochromatosis). Most evaluated patients had some degree of decrease in intelligence.
Genetics
The syndrome appears to be due to mutations in the gene tetratricopeptide repeat domain 37 (TTC37) which encodes the protein Thespin or the SKIV2L gene. This gene is expressed is in the adrenal gland, amniotic fluid, bladder, blood, bone, bone marrow, brain, cervix, connective tissue, ear, epididymis, eye, heart, intestine, kidney, liver, lung, lymph nodes, mammary glands, mouth, muscle, nerve, | [
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wikipedia | https://en.wikipedia.org/wiki/Tricho-hepato-enteric_syndrome | 6Dm1ALx | Tricho-hepato-enteric syndrome | C1857276 | 15 | tricho-hepato-enteric syndrome. of decrease in intelligence.
Genetics
The syndrome appears to be due to mutations in the gene tetratricopeptide repeat domain 37 (TTC37) which encodes the protein Thespin or the SKIV2L gene. This gene is expressed is in the adrenal gland, amniotic fluid, bladder, blood, bone, bone marrow, brain, cervix, connective tissue, ear, epididymis, eye, heart, intestine, kidney, liver, lung, lymph nodes, mammary glands, mouth, muscle, nerve, oesophagus, ovary, pancreas, pharynx, placenta, prostate, pituitary gland, salivary gland, testis, thyroid, tonsil, thymus, trachea, skin, uterus, spleen, spinal cord, stomach and vascular tissue. It is also expressed in ascites and various embryonic tissues. It is expressed at high level in the intestine, lung, lymph nodes, pituitary and vascular tissues. This gene is also known as KIAA0372, MGC32587 | [
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wikipedia | https://en.wikipedia.org/wiki/Tricho-hepato-enteric_syndrome | 6Dm1ALx | Tricho-hepato-enteric syndrome | C1857276 | 15 | tricho-hepato-enteric syndrome. nodes, mammary glands, mouth, muscle, nerve, oesophagus, ovary, pancreas, pharynx, placenta, prostate, pituitary gland, salivary gland, testis, thyroid, tonsil, thymus, trachea, skin, uterus, spleen, spinal cord, stomach and vascular tissue. It is also expressed in ascites and various embryonic tissues. It is expressed at high level in the intestine, lung, lymph nodes, pituitary and vascular tissues. This gene is also known as KIAA0372, MGC32587 and TPR repeat protein 37.
This gene is located on the Crick (minus) strand of the long arm of chromosome 5 (5q15). The gene is 91,113 bases in length and encodes a protein of 1564 amino acid residues with twenty tetratricopeptide repeats. It has 43 exons of which exons 1, 2 and 3 are non coding. The predicted molecular weight of the protein is 175.486 kiloDaltons and its | [
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wikipedia | https://en.wikipedia.org/wiki/Tricho-hepato-enteric_syndrome | 6Dm1ALx | Tricho-hepato-enteric syndrome | C1857276 | 15 | tricho-hepato-enteric syndrome. known as KIAA0372, MGC32587 and TPR repeat protein 37.
This gene is located on the Crick (minus) strand of the long arm of chromosome 5 (5q15). The gene is 91,113 bases in length and encodes a protein of 1564 amino acid residues with twenty tetratricopeptide repeats. It has 43 exons of which exons 1, 2 and 3 are non coding. The predicted molecular weight of the protein is 175.486 kiloDaltons and its predicted pI is 7.47. Its function is unknown but it may have adenylate cyclase activity and calcium- and calmodulin-responsive adenylate cyclase activity. A homolog has been identified in the frog (Xenopus tropicalis), the mouse (Mus musculus) and the rat (Rattus norvegicus). In the mouse this gene is located on chromosome 13.
Diagnosis
Microscopic analysis of the hair shaft showing breaks located at nodes in the hair | [
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wikipedia | https://en.wikipedia.org/wiki/Tricho-hepato-enteric_syndrome | 6Dm1ALx | Tricho-hepato-enteric syndrome | C1857276 | 15 | tricho-hepato-enteric syndrome. the protein is 175.486 kiloDaltons and its predicted pI is 7.47. Its function is unknown but it may have adenylate cyclase activity and calcium- and calmodulin-responsive adenylate cyclase activity. A homolog has been identified in the frog (Xenopus tropicalis), the mouse (Mus musculus) and the rat (Rattus norvegicus). In the mouse this gene is located on chromosome 13.
Diagnosis
Microscopic analysis of the hair shaft showing breaks located at nodes in the hair (trichorrhexis nodosa) and longitudinal breaks.
Small intestine biopsy of a patient with THE syndrome showing severe villous atrophy with intense mononuclear cell infiltration in the lamina propria. (Courtesy of Prof. Michel Peuchmaur, Hôpital Robert Debré, Paris, France)
Facial features
The typical facial features are low-set ears, prominent eyes with hypertelorism, broad flat nose, prominent forehead and large mouth | [
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wikipedia | https://en.wikipedia.org/wiki/Tricho-hepato-enteric_syndrome | 6Dm1ALx | Tricho-hepato-enteric syndrome | C1857276 | 15 | tricho-hepato-enteric syndrome. the hair shaft showing breaks located at nodes in the hair (trichorrhexis nodosa) and longitudinal breaks.
Small intestine biopsy of a patient with THE syndrome showing severe villous atrophy with intense mononuclear cell infiltration in the lamina propria. (Courtesy of Prof. Michel Peuchmaur, Hôpital Robert Debré, Paris, France)
Facial features
The typical facial features are low-set ears, prominent eyes with hypertelorism, broad flat nose, prominent forehead and large mouth.
Liver
There may be fibrosis with bile duct proliferation, occasional giant cells and regenerative parenchymal nodules. Siderosis is common.
Small bowel
Microscopic examination of a biopsy of the small bowel in these patients shows villous atrophy with low or no mononuclear cell infiltration of the lamina propria nor specific abnormalities involving the epithelium. The amount of villous atrophy does not explain the severity of the diarrhea.
Studies of enterocyte brush-border ion transporter proteins (sodium-hydrogen exchanger 2 | [
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wikipedia | https://en.wikipedia.org/wiki/Tricho-hepato-enteric_syndrome | 6Dm1ALx | Tricho-hepato-enteric syndrome | C1857276 | 15 | tricho-hepato-enteric syndrome. m, broad flat nose, prominent forehead and large mouth.
Liver
There may be fibrosis with bile duct proliferation, occasional giant cells and regenerative parenchymal nodules. Siderosis is common.
Small bowel
Microscopic examination of a biopsy of the small bowel in these patients shows villous atrophy with low or no mononuclear cell infiltration of the lamina propria nor specific abnormalities involving the epithelium. The amount of villous atrophy does not explain the severity of the diarrhea.
Studies of enterocyte brush-border ion transporter proteins (sodium-hydrogen exchanger 2, sodium-hydrogen exchanger 3, aquaporin 7, sodium iodide symporter and hydrogen potassium adenosine triphosphatase) showed reduced expression or mislocalization in all patients with different profiles for each.
Hair
Microscopic analysis of the hair shows twisted hairs of unequal size and different shapes (pili torti, aniso- and poikilotrichosis), longitudinal breaks and breaks located at nodes (trichorrhexis nodosa). Scanning electron microscopy | [
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] |
wikipedia | https://en.wikipedia.org/wiki/Tricho-hepato-enteric_syndrome | 6Dm1ALx | Tricho-hepato-enteric syndrome | C1857276 | 15 | tricho-hepato-enteric syndrome. -border ion transporter proteins (sodium-hydrogen exchanger 2, sodium-hydrogen exchanger 3, aquaporin 7, sodium iodide symporter and hydrogen potassium adenosine triphosphatase) showed reduced expression or mislocalization in all patients with different profiles for each.
Hair
Microscopic analysis of the hair shows twisted hairs of unequal size and different shapes (pili torti, aniso- and poikilotrichosis), longitudinal breaks and breaks located at nodes (trichorrhexis nodosa). Scanning electron microscopy might reveal hair budding (trichorrhexis blastysis). Biochemical analysis may reveal sulfur-deficient brittle hair (trichothiodystrophy; note that disulfide bonds determine hair waviness).
Platelets
Platelets may be enlarged. The membrane surface connected canalicular system is disrupted with prominent tubules and small membranous vesicles. Alpha granules may be missing from the platelets. Despite these abnormalities there is no increased tendency to bleed in this syndrome.
Other
More | [
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wikipedia | https://en.wikipedia.org/wiki/Tricho-hepato-enteric_syndrome | 6Dm1ALx | Tricho-hepato-enteric syndrome | C1857276 | 15 | tricho-hepato-enteric syndrome. trichorrhexis nodosa). Scanning electron microscopy might reveal hair budding (trichorrhexis blastysis). Biochemical analysis may reveal sulfur-deficient brittle hair (trichothiodystrophy; note that disulfide bonds determine hair waviness).
Platelets
Platelets may be enlarged. The membrane surface connected canalicular system is disrupted with prominent tubules and small membranous vesicles. Alpha granules may be missing from the platelets. Despite these abnormalities there is no increased tendency to bleed in this syndrome.
Other
More than 90% of patients present immune defects. Low immunoglobulin level, a defect in antibody production after vaccination, monoclonal hyper IgA, and low lymphocyte count have been reported. In these cases, some patients may need immunoglobulin supplementation.
Treatment
No specific treatment or cure exists. Affected children usually need total parenteral nutrition through a central venous catheter. Further worsening of liver damage should however be avoided if possible. Diarrhea will likely continue even though food stops passing through the | [
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wikipedia | https://en.wikipedia.org/wiki/Tricho-hepato-enteric_syndrome | 6Dm1ALx | Tricho-hepato-enteric syndrome | C1857276 | 15 | tricho-hepato-enteric syndrome. increased tendency to bleed in this syndrome.
Other
More than 90% of patients present immune defects. Low immunoglobulin level, a defect in antibody production after vaccination, monoclonal hyper IgA, and low lymphocyte count have been reported. In these cases, some patients may need immunoglobulin supplementation.
Treatment
No specific treatment or cure exists. Affected children usually need total parenteral nutrition through a central venous catheter. Further worsening of liver damage should however be avoided if possible. Diarrhea will likely continue even though food stops passing through the gastrointestinal system. They can subsequently be managed with tube feeding, and some may be weaned from nutritional support during adolescence.
Epidemiology
Tricho-hepato-enteric syndrome is estimated to affect 1 in 300,000 to 400,000 live births in Western Europe. This syndrome was first reported in 1982 with a report on 2 siblings, and as of 2008 there were around 25 published cases in medical journals. There seem to be no racial differences in its occurrence | [
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wikipedia | https://en.wikipedia.org/wiki/Tricho-hepato-enteric_syndrome | 6Dm1ALx | Tricho-hepato-enteric syndrome | C1857276 | 15 | tricho-hepato-enteric syndrome. will likely continue even though food stops passing through the gastrointestinal system. They can subsequently be managed with tube feeding, and some may be weaned from nutritional support during adolescence.
Epidemiology
Tricho-hepato-enteric syndrome is estimated to affect 1 in 300,000 to 400,000 live births in Western Europe. This syndrome was first reported in 1982 with a report on 2 siblings, and as of 2008 there were around 25 published cases in medical journals. There seem to be no racial differences in its occurrence. It might be more common, as many genetic diseases, in areas with high levels of consanguinity.
Footnotes
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wikipedia | https://en.wikipedia.org/wiki/Tricho-hepato-enteric_syndrome | 6Dm1ALx | Tricho-hepato-enteric syndrome | C1857276 | 15 | tricho-hepato-enteric syndrome. . There seem to be no racial differences in its occurrence. It might be more common, as many genetic diseases, in areas with high levels of consanguinity.
Footnotes
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wikipedia | https://en.wikipedia.org/wiki/Tricho-hepato-enteric_syndrome | 6Dm1ALx | Tricho-hepato-enteric syndrome | C1857276 | 15 | tricho-hepato-enteric syndrome. ;font-size:100%}.mw-parser-output .cs1-visible-error{font-size:100%}.mw-parser-output .cs1-maint{display:none;color:#33aa33;margin-left:0.3em}.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font | [
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wikipedia | https://en.wikipedia.org/wiki/Tricho-hepato-enteric_syndrome | 6Dm1ALx | Tricho-hepato-enteric syndrome | C1857276 | 15 | tricho-hepato-enteric syndrome. -parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}Fabre A, André N, Breton A, Broué P, Badens C, Roquelaure B (March 2007). "Intractable diarrhea with "phenotypic anomalies" and tricho-hepato-enteric syndrome: two names for the same disorder". Am. J. Med. Genet. A. 143 (6): 584–8. doi:10.1002 | [
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wikipedia | https://en.wikipedia.org/wiki/Tricho-hepato-enteric_syndrome | 6Dm1ALx | Tricho-hepato-enteric syndrome | C1857276 | 15 | tricho-hepato-enteric syndrome. .citation .mw-selflink{font-weight:inherit}Fabre A, André N, Breton A, Broué P, Badens C, Roquelaure B (March 2007). "Intractable diarrhea with "phenotypic anomalies" and tricho-hepato-enteric syndrome: two names for the same disorder". Am. J. Med. Genet. A. 143 (6): 584–8. doi:10.1002/ajmg.a.31634. PMID 17318842.
^ a b c Goulet O, Vinson C, Roquelaure B, Brousse N, Bodemer C, Cézard JP (2008). "Syndromic (phenotypic) diarrhea in early infancy". Orphanet J Rare Dis. 3: 6. doi:10.1186/1750-1172-3- | [
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