Waardenburg syndrome |
Classification and external resources |
ICD-10 |
E70.3 (ILDS E70.32) |
ICD-9 |
270.2 |
DiseasesDB |
14021 33475 |
MedlinePlus |
001428 |
eMedicine |
ped/2422 derm/690 |
MeSH |
D014849 |
Waardenburg syndrome (also Waardenburg Shah Syndrome, Waardenburg-Klein syndrome, Mende's syndrome II, Van der Hoeve-Halbertsma-Waardenburg syndrome, Ptosis-Epicanthus syndrome, Van der Hoeve-Halbertsma-Gualdi syndrome, Waardenburg type Pierpont,[5] Van der Hoeve-Waardenburg-Klein syndrome, Waardenburg's syndrome II and Vogt’s syndrome.) is a rare genetic disorder most often characterized by varying degrees of deafness, minor defects in structures arising from the neural crest, and pigmentation anomalies.
It was first described in 1951[1]
Contents
- 1 Eponyms and classification
- 2 Signs and symptoms
- 3 Epidemiology
- 4 Classification
- 5 Symptoms
- 6 Inheritance
- 7 Treatment
- 8 In animals
- 9 In Popular Culture
- 10 Other Contributors
- 11 See also
- 12 References
- 13 External links
|
Eponyms and classification
Waardenburg syndrome is named after Dutch ophthalmologist Petrus Johannes Waardenburg (1886–1979), who described the syndrome in detail in 1951.[1][2] The condition he described is now categorized as WS1. Swiss ophthalmologist David Klein also made contributions towards the understanding of the syndrome.[3]
WS2 was identified in 1971, to describe cases where "dystopia canthorum" did not present.[4] WS2 is now split into subtypes, based upon the gene responsible.
Other types have been identified, but they are less common.
Signs and symptoms
There are five major and five minor diagnostic criteria for Waardenburg syndrome.
Major:
- sensorineural hearing loss
- iris pigmentary abnormality (two eyes different color or iris bicolor or characteristic brilliant blue iris)
- hair hypopigmentation (white forelock or white hairs at other sites on the body)
- dystopia canthorum (lateral displacement of inner canthi)
- first‐degree relative previously diagnosed with Waardenburg syndrome
Minor:
- skin hypopigmentation (congenital leukoderma/white skin patches)
- medial eyebrow flare (synophrys)
- broad nasal root
- hypoplasia alae nasi
- premature graying of the hair (before age 30).
Epidemiology
The overall incidence is ~1/42,000 to 1/50,000 people. Types I and II are the most common types of the syndrome, whereas types III and IV are rare. Type 4 is also known as Waardenburg‐Shah syndrome (association of Waardenburg syndrome with Hirschsprung disease).
Type 4 is rare with only 48 cases reported up to 2002.[5]
About 1 in 30 students in schools for the deaf have Waardenburg syndrome. All races and both sexes are affected equally. The highly variable presentation of the syndrome makes it difficult to arrive at precise figures for its prevalence.
Classification
Subtypes of the syndrome are traceable to different genetic variations:
Type |
OMIM |
Gene |
Locus |
Also known as |
Type I, WS1 |
193500 |
PAX3 |
2q35 |
- |
Type IIa, WS2A (originally WS2) |
193510 |
MITF |
3p14.1-p12.3 |
- |
Type IIb, WS2B |
600193 |
WS2B |
1p21-p13.3 |
- |
Type IIc, WS2C |
606662 |
WS2C |
8p23 |
- |
Type IId, WS2D (very rare) |
608890 |
SNAI2 |
8q11 |
- |
Type III, WS3 |
148820 |
PAX3 |
2q35 |
Klein-Waardenburg syndrome |
Type IVa, WS4A |
277580 |
EDNRB |
13q22 |
|
Type IVb, WS4B |
613265 |
EDN3 |
20q13 |
|
Type IVc, WS4C |
613266 |
SOX10 |
22q13 |
|
Symptoms
Facial morphology of Waardenburg syndrome
Symptoms vary from one type of the syndrome to another and from one patient to another, but they include:
- Very pale or brilliantly blue eyes, eyes of two different colors (complete heterochromia), or eyes with one iris having two different colours (sectoral heterochromia);
- A forelock of white hair (poliosis), or premature graying of the hair;
- Appearance of wide-set eyes due to a prominent, broad nasal root (dystopia canthorum)—particularly associated with type I) also known as telecanthus;
- Moderate to profound hearing loss (higher frequency associated with type II);
- A low hairline and eyebrows that touch in the middle.
- Patches of white pigmentation on the skin have been observed in some people. Sometimes, abnormalities of the arms, associated with type III, have been observed.
- Type IV may include neurologic manifestations.
Waardenburg syndrome has also been associated with a variety of other congenital disorders, such as intestinal and spinal defects, elevation of the scapula, and cleft lip and palate. Sometimes this is concurrent with Hirschsprung disease.
Inheritance
This condition is usually inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to cause the disorder. In most cases, an affected person has one parent with the condition. A small percentage of cases result from new mutations in the gene; these cases occur in people with no history of the disorder in their family.
Some cases of type II and type IV Waardenburg syndrome appear to have an autosomal recessive pattern of inheritance, which means two copies of the gene must be altered for a person to be affected by the disorder. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene.
-
Waardenburg syndrome is usually inherited in an autosomal dominant pattern.
-
Types II and IV Waardenburg syndrome may sometimes have an autosomal recessive pattern of inheritance.
Treatment
There is currently no treatment or cure for Waardenburg syndrome. The symptom most likely to be of practical importance is deafness, and this is treated as any other irreversible deafness would be. In marked cases there may be cosmetic issues. Other abnormalities (neurological, structural, Hirschsprung disease) associated with the syndrome are treated symptomatically.
In animals
Waardenburg syndrome is known to occur in ferrets. The affected animal will usually have a small white stripe along the top or back of its head, sometimes down the back of the neck (known as a blaze) or a solid white head (from nose to shoulders; ferrets with this are known as a panda marked ferret) and a somewhat, although barely noticeably, flatter skull than normal ferrets. As a ferret's sense of hearing is poor to begin with it is not easily noticeable except for when the affected animal does not react to loud noises that non-affected ones will respond to. As the disorder is easily spread to offspring, the affected animal will not be used for breeding by private, reputable breeders, although it may still be neutered and sold as a pet. However, largely as a result of mass-breeding due to the "exotic" markings it gives (when compared to a standard sable/pole cat marked or albino ferret), 75% of US ferrets with a blaze or white head sold from pet stores are deaf.[6]
In Popular Culture
In the season 6 episode of Bones (TV Series), 'The Signs in the Silence', the team must solve a case in which the suspected killer has Waardenburg syndrome.
Enzo Macleod, protagonist of Peter May's series The Enzo Files, has Waardenburg syndrome. His eyes are different colors and he has a white streak in his hair. See pp. 17-18 of "Extraordinary People" (2006) by Peter Mays.
Other Contributors
- Waardenburg-Klein syndrome is named after Petrus Johannes Waardenburg (1886–1979), a Dutch ophthalmologist and geneticist, and David Klein, a Swiss human geneticist and ophthalmologist.
- Mende's syndrome II is named after Irmgard Mende (1938-), a German-American physician.
- Van der Hoeve-Halbertsma-Waardenburg Syndrome is named after Jan Van der Hoeve (1878-1952), a Dutch ophthalmologist, Nicolaas Adolf Halbertsma (1889-1968), Dutch physician and Petrus Johannes Waardenburg (1886–1979).
- Van der Hoeve-Halbertsma-Gualdi syndrome is named for Jan Van der Hoeve (1878-1952), Nicolaas Adolf Halbertsma (1889-1968) and Vincenzo Gualdi (1891-1976),an Italian physician.
- Vogt’s syndrome is named for Cecile Vogt (1875-1962), a French-German neuropathologist.
See also
- Chediak–Higashi syndrome
- List of cutaneous conditions
References
- ^ a b Waardenburg PJ (September 1951). "A new syndrome combining developmental anomalies of the eyelids, eyebrows and noseroot with pigmentary anomalies of the iris and head hair and with congenital deafness; Dystopia canthi medialis et punctorum lacrimalium lateroversa, hyperplasia supercilii medialis et radicis nasi, heterochromia iridum totaliis sive partialis, albinismus circumscriptus (leucismus, polioss) et surditas congenita (surdimutitas)". Am. J. Hum. Genet. 3 (3): 195–253. PMC 1716407. PMID 14902764. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1716407/.
- ^ doctor/1012 at Who Named It?
- ^ Klein-Waardenburg syndrome at Who Named It?
- ^ Arias S (1971). "Genetic heterogeneity in the Waardenburg syndrome". Birth Defects Orig. Artic. Ser. 07 (4): 87–101. PMID 5006208.
- ^ Egbalian F (2008). "Waardenburg Shah syndrome; A case report and review of the literature". Iran J Ped 18 (1): 71–7.
- ^ Erika Matulich, Ph.D, Cypresskeep.com
External links
- GeneReviews/NCBI/NIH/UW entry on Waardenburg Syndrome Type I
- OMIM Genetic disorder catalog — Waardenburg syndrome
Inborn error of amino acid metabolism (E70–E72, 270)
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K→acetyl-CoA |
Lysine/straight chain
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- Glutaric acidemia type 1
- type 2
- Hyperlysinemia
- Pipecolic acidemia
- Saccharopinuria
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Leucine
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- Maple syrup urine disease
- Isovaleric acidemia
- 3-Methylcrotonyl-CoA carboxylase deficiency
- 3-hydroxy-3-methylglutaryl-CoA lyase deficiency
- 3-Methylglutaconic aciduria 1
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Tryptophan
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G |
G→pyruvate→citrate
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Glycine
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- Sarcosinemia
- D-Glyceric acidemia
- Glutathione synthetase deficiency
- Glycine→Creatine: GAMT deficiency
- Glycine encephalopathy
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G→glutamate→
α-ketoglutarate
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Histidine
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- Carnosinemia
- Histidinemia
- Urocanic aciduria
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Proline
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- Hyperprolinemia
- Prolidase deficiency
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Glutamate/glutamine
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G→propionyl-CoA→
succinyl-CoA
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Valine
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- Maple syrup urine disease
- Hypervalinemia
- Isobutyryl-CoA dehydrogenase deficiency
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Isoleucine
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- Maple syrup urine disease
- Beta-ketothiolase deficiency
- 2-Methylbutyryl-CoA dehydrogenase deficiency
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Methionine
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- Hypermethioninemia
- Homocystinuria
- Cystathioninuria
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General BC/OA
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- Propionic acidemia
- Methylmalonic acidemia
- Methylmalonyl-CoA mutase deficiency
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G→fumarate
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Phenylalanine/tyrosine
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Phenylketonuria
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- Tetrahydrobiopterin deficiency
- 6-Pyruvoyltetrahydropterin synthase deficiency
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Tyrosinemia
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- Type II tyrosinemia
- Type III tyrosinemia/Hawkinsinuria
- Alkaptonuria/Ochronosis
- Type I tyrosinemia
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Tyrosine→Melanin
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- Albinism: Ocular albinism (1)
- Oculocutaneous albinism (Hermansky–Pudlak syndrome)
- Waardenburg syndrome
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Tyrosine→Norepinephrine
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- Dopamine beta hydroxylase deficiency
- reverse: Brunner syndrome
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G→oxaloacetate
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Urea cycle/Hyperammonemia
(arginine
|
- N-Acetylglutamate synthase deficiency
- Carbamoyl phosphate synthetase I deficiency
- Ornithine transcarbamylase deficiency/translocase deficiency
- Citrullinemia
- Argininosuccinic aciduria
- Argininemia
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Transport/
IE of RTT |
- Solute carrier family: Cystinuria
- Hartnup disease
- Lysinuric protein intolerance
- Iminoglycinuria
- Fanconi syndrome: Oculocerebrorenal syndrome
- Cystinosis
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Other |
- Trimethylaminuria
- 2-Hydroxyglutaric aciduria
- Fumarase deficiency
- Ethylmalonic encephalopathy
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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Pigmentation disorders/Dyschromia (L80–L81, 709.0)
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Hypo-/
leucism |
Loss of melanocytes
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vitiligo: Quadrichrome vitiligo · Vitiligo ponctué · syndromic (Alezzandrini syndrome · Vogt–Koyanagi–Harada syndrome)
melanocyte development: Piebaldism · Waardenburg syndrome · Tietz syndrome
|
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Loss of melanin/
amelanism
|
albinism: Oculocutaneous albinism · Ocular albinism
melanosome transfer: Hermansky–Pudlak syndrome · Chédiak–Higashi syndrome · Griscelli syndrome (Elejalde syndrome · Griscelli syndrome type 2 · Griscelli syndrome type 3)
other: Cross syndrome · ABCD syndrome · Albinism–deafness syndrome · Idiopathic guttate hypomelanosis · Phylloid hypomelanosis · Progressive macular hypomelanosis
|
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Leukoderma w/o
hypomelanosis
|
Vasospastic macule · Woronoff's ring · Nevus anemicus
|
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Ungrouped
|
ungrouped: Nevus depigmentosus · Postinflammatory hypopigmentation · Pityriasis alba · Vagabond's leukomelanoderma · Yemenite deaf-blind hypopigmentation syndrome · Wende–Bauckus syndrome
|
|
|
Hyper- |
Melanin/
Melanosis/
Melanism
|
Reticulated
|
Dermatopathia pigmentosa reticularis · Pigmentatio reticularis faciei et colli · Reticulate acropigmentation of Kitamura · Reticular pigmented anomaly of the flexures · Naegeli–Franceschetti–Jadassohn syndrome · Dyskeratosis congenita · X-linked reticulate pigmentary disorder · Galli–Galli disease · Revesz syndrome
|
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Diffuse/
circumscribed
|
Lentigo/Lentiginosis: Lentigo simplex · Liver spot · Centrofacial lentiginosis · Generalized lentiginosis · Inherited patterned lentiginosis in black persons · Ink spot lentigo · Lentigo maligna · Mucosal lentigines · Partial unilateral lentiginosis · PUVA lentigines
Melasma · Erythema dyschromicum perstans · Lichen planus pigmentosus · Café au lait spot · Poikiloderma (Poikiloderma of Civatte · Poikiloderma vasculare atrophicans) · Riehl melanosis
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Linear
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Incontinentia pigmenti · Scratch dermatitis · Shiitake mushroom dermatitis
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Other/ungrouped
|
Acanthosis nigricans (Acral acanthotic anomaly) · Freckle · Familial progressive hyperpigmentation · Pallister–Killian syndrome · Periorbital hyperpigmentation · Photoleukomelanodermatitis of Kobori · Postinflammatory hyperpigmentation · Transient neonatal pustular melanosis
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Other
pigments
|
iron: Hemochromatosis · Iron metallic discoloration · Pigmented purpuric dermatosis (Schamberg disease, Majocchi's disease, Gougerot–Blum syndrome, Doucas and Kapetanakis pigmented purpura/Eczematid-like purpura of Doucas and Kapetanakis, Lichen aureus, Angioma serpiginosum) · Hemosiderin hyperpigmentation
other metals: Argyria · Chrysiasis · Arsenic poisoning · Lead poisoning · Titanium metallic discoloration
other: Carotenosis · Tattoo · Tar melanosis
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Dyschromatoses |
Dyschromatosis symmetrica hereditaria · Dyschromatosis universalis hereditaria
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|
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noco (i/b/d/q/u/r/p/m/k/v/f)/cong/tumr (n/e/d), sysi/epon
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proc, drug (D2/3/4/5/8/11)
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Genetic disorder, protein biosynthesis: Transcription factor/coregulator deficiencies
|
|
(1) Basic domains |
1.2: Feingold syndrome · Saethre–Chotzen syndrome
1.3: Tietz syndrome
|
|
(2) Zinc finger
DNA-binding domains |
2.1 (Intracellular receptor): Thyroid hormone resistance · Androgen insensitivity syndrome (PAIS, MAIS, CAIS) · Kennedy's disease · PHA1AD pseudohypoaldosteronism · Estrogen insensitivity syndrome · X-linked adrenal hypoplasia congenita · MODY 1 · Familial partial lipodystrophy 3 · SF1 XY gonadal dysgenesis
2.2: Barakat syndrome · Tricho–rhino–phalangeal syndrome
2.3: Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome · Denys–Drash syndrome · Duane-radial ray syndrome · MODY 7 · MRX 89 · Townes–Brocks syndrome · Acrocallosal syndrome · Myotonic dystrophy 2
2.5: Autoimmune polyendocrine syndrome type 1
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(3) Helix-turn-helix domains |
3.1: ARX (Ohtahara syndrome, Lissencephaly X2) · HLXB9 (Currarino syndrome) · HOXD13 (SPD1 Synpolydactyly) · IPF1 (MODY 4) · LMX1B (Nail–patella syndrome) · MSX1 (Tooth and nail syndrome, OFC5) · PITX2 (Axenfeld syndrome 1) · POU4F3 (DFNA15) · POU3F4 (DFNX2) · ZEB1 (Posterior polymorphous corneal dystrophy 3, Fuchs' dystrophy 3) · ZEB2 (Mowat–Wilson syndrome)
3.2: PAX2 (Papillorenal syndrome) · PAX3 (Waardenburg syndrome 1&3) · PAX4 (MODY 9) · PAX6 (Gillespie syndrome, Coloboma of optic nerve) · PAX8 (Congenital hypothyroidism 2) · PAX9 (STHAG3)
3.3: FOXC1 (Axenfeld syndrome 3, Iridogoniodysgenesis, dominant type) · FOXC2 (Lymphedema–distichiasis syndrome) · FOXE1 (Bamforth–Lazarus syndrome) · FOXE3 (Anterior segment mesenchymal dysgenesis) · FOXF1 (ACD/MPV) · FOXI1 (Enlarged vestibular aqueduct) · FOXL2 (Premature ovarian failure 3) · FOXP3 (IPEX)
3.5: IRF6 (Van der Woude syndrome, Popliteal pterygium syndrome)
|
|
(4) β-Scaffold factors
with minor groove contacts |
4.2: Hyperimmunoglobulin E syndrome
4.3: Holt–Oram syndrome · Li–Fraumeni syndrome · Ulnar–mammary syndrome
4.7: Campomelic dysplasia · MODY 3 · MODY 5 · SF1 (SRY XY gonadal dysgenesis, Premature ovarian failure 7) · SOX10 (Waardenburg syndrome 4c, Yemenite deaf-blind hypopigmentation syndrome)
4.11: Cleidocranial dysostosis
|
|
(0) Other transcription factors |
0.6: Kabuki syndrome
|
|
Ungrouped |
TCF4 (Pitt–Hopkins syndrome) · ZFP57 (TNDM1) · TP63 (Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8)
|
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Transcription coregulators |
coactivator: CREBBP (Rubinstein–Taybi syndrome)
corepressor: HR (Atrichia with papular lesions)
|
|
see also transcription factors
- B structural
- perx
- skel
- cili
- mito
- nucl
- sclr
- DNA/RNA/protein synthesis
- membrane
- transduction
- trfk
|
|
Genetic disorder, membrane: cell surface receptor deficiencies
|
|
G protein-coupled receptor
(including hormone) |
Class A |
- TSHR (Congenital hypothyroidism 1)
- LHCGR (Male-limited precocious puberty)
- FSHR (XX gonadal dysgenesis)
- EDNRB (ABCD syndrome, Waardenburg syndrome 4a, Hirschsprung's disease 2)
- AVPR2 (Nephrogenic diabetes insipidus 1)
- PTGER2 (Aspirin-induced asthma)
|
|
Class B |
- PTH1R (Jansen's metaphyseal chondrodysplasia)
|
|
Class C |
- CASR (Familial hypocalciuric hypercalcemia)
|
|
Class F |
- FZD4 (Familial exudative vitreoretinopathy 1)
|
|
|
Enzyme-linked receptor
(including
growth factor) |
RTK |
- ROR2 (Robinow syndrome)
- FGFR1 (Pfeiffer syndrome, KAL2 Kallmann syndrome)
- FGFR2 (Apert syndrome, Antley-Bixler syndrome, Pfeiffer syndrome, Crouzon syndrome, Jackson-Weiss syndrome)
- FGFR3 (Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia, Muenke syndrome)
- INSR (Donohue syndrome
- Rabson–Mendenhall syndrome)
- NTRK1 (Congenital insensitivity to pain with anhidrosis)
- KIT (KIT Piebaldism, Gastrointestinal stromal tumor)
|
|
STPK |
- AMHR2 (Persistent Mullerian duct syndrome II)
- TGF beta receptors: Endoglin/Alk-1/SMAD4 (Hereditary hemorrhagic telangiectasia)
- TGFBR1/TGFBR2 (Loeys-Dietz syndrome)
|
|
GC |
- GUCY2D (Leber's congenital amaurosis 1)
|
|
|
JAK-STAT |
- Type I cytokine receptor: GH (Laron syndrome)
- CSF2RA (Surfactant metabolism dysfunction 4)
- MPL (Congenital amegakaryocytic thrombocytopenia)
|
|
TNF receptor |
- TNFRSF1A (TNF receptor associated periodic syndrome)
- TNFRSF13B (Selective immunoglobulin A deficiency 2)
- TNFRSF5 (Hyper-IgM syndrome type 3)
- TNFRSF13C (CVID4)
- TNFRSF13B (CVID2)
- TNFRSF6 (Autoimmune lymphoproliferative syndrome 1A)
|
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Lipid receptor |
- LRP: LRP2 (Donnai-Barrow syndrome)
- LRP4 (Cenani Lenz syndactylism)
- LRP5 (Worth syndrome, Familial exudative vitreoretinopathy 4, Osteopetrosis 1)
- LDLR (LDLR Familial hypercholesterolemia)
|
|
Other/ungrouped |
- Immunoglobulin superfamily: AGM3, 6
- Integrin: LAD1
- Glanzmann's thrombasthenia
- Junctional epidermolysis bullosa with pyloric atresia
EDAR (EDAR Hypohidrotic ectodermal dysplasia)
- PTCH1 (Nevoid basal cell carcinoma syndrome)
- BMPR1A (BMPR1A Juvenile polyposis syndrome)
- IL2RG (X-linked severe combined immunodeficiency)
|
|
- See also
- cell surface receptors
- B structural
- perx
- skel
- cili
- mito
- nucl
- sclr
- DNA/RNA/protein synthesis
- membrane
- transduction
- trfk
|
|
Extracellular ligand disorders
|
|
Cytokine |
- EDA Hypohidrotic ectodermal dysplasia
- Camurati-Engelmann disease
|
|
Ephrin |
- Craniofrontonasal dysplasia
|
|
WNT |
|
|
TGF |
|
|
Fas ligand |
- Autoimmune lymphoproliferative syndrome 1B
|
|
Endothelin |
- EDN3
- Waardenburg syndrome IVb
- Hirschsprung's disease 4
|
|
Other |
- DHH (DHH XY gonadal dysgenesis)
- BMP15 (Premature ovarian failure 4)
- TSHB (Congenital hypothyroidism 4)
|
|
- See also
- intercellular signaling peptides and proteins
- B structural
- perx
- skel
- cili
- mito
- nucl
- sclr
- DNA/RNA/protein synthesis
- membrane
- transduction
- trfk
|
|