Waardenburg syndrome

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. Disruptions in myogenesis, particularly mutations in Pax3, can cause Waardenburg syndrome I and III.
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[edit]

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.
Mutations in the EDN3, EDNRB, MITF, PAX3, SNAI2, and SOX10 are the genes that are affected from Waardenburg Syndrome. Some of these genes are involved in the making of melanocytes, which makes the pigment melanin. Melanin is an important pigment in the development of hair, eye color, skin, and functions of the inner ear. So the mutation of these genes can lead to abnormal pigmentation and hearing loss.^[5] PAX3 and MTIF gene mutation occurs in type I and II (WS1 and WS2). Type III (WS3) shows mutations of the PAX3 gene also. SOX10, EDN3, or EDNRB gene mutations occur in type IV. Type IV (WS4) can also affect portions of nerve cell development that potentially can lead to intestinal issues.

Signs and symptoms[edit]

There are five major and five minor diagnostic criteria for Waardenburg syndrome.
Major:

• sensorineural hearing loss
• iris pigmentary abnormality ( heterochromia iridum- different colors of iris in two eyes or heterochromia iridis - two different colors of iris in same eye or characteristic brilliant blue iris)
• hair hypopigmentation (white forelock or white hairs at other sites on the body) (poliosis)
• dystopia canthorum (lateral displacement of inner canthi)
• first‐degree relative previously diagnosed with Waardenburg syndrome

Minor:

• skin hypopigmentation (congenital leukoderma/white skin patches - Vitiligo )
• medial eyebrow flare (synophrys)
• broad nasal root (dystopia canthorum)
• hypoplasia alae nasi
• premature graying of the hair (before age 30).

Epidemiology[edit]

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.^[6]
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[edit]

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[edit]

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;^[7]
• 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.
Type I is associated with more permanent hearing loss as for Type III over time hearing will be lost. Both are similar physically but there is no way to diagnose by eye, but to distinguish differences genetic testing is needed. Type II is most common out of all and its phenotypes are permanent hearing loss and heterochromia iridis (two different colored eyes) While Type IV has most of the symptoms associated with type II patients also tend to develop Hirschsprung's disease, intestinal problems, which can be life-threatening and surgery is needed for enlarged colon and failure to pass feces.^[8]

Inheritance[edit]

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.

Types I and III inheritance of this trait is autosomal dominant. There is a 50% chance that a child of an affected parent will be affected. Symptoms vary and so the extremity of symptoms cannot be determined. Types II and IV is autosomal recessive, symptoms are not definite they vary just as the other type’s symptoms will. A study was done on a rare case of a double heterozygous child with each parent having only single mutations in MTIF or PAX3. The affect of double heterozygous mutations in the genes MTIF and PAX3 in WS1 and WS2 can increase the pigment-affected symptoms. It leads to the conclusion that the double mutation of MTIF is associated with the extremity of Waardenburg Syndrome and may affect the phenotypes or symptoms of the syndrome ^[9]

Treatment[edit]

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[edit]

Waardenburg syndrome is known to occur in ferrets. The affected individual will usually have a small white stripe along the top or back of the head and sometimes down the back of the neck (this is known as a "blaze" coat pattern), or a solid white head from nose to shoulders (known as a "panda" coat pattern). The ferret will often have a very slightly flatter skull than ferrets without the syndrome and may have unusually wide-set eyes. As a ferret's sense of hearing is poor to begin with, associated deafness is not easily noticeable except for a lack of reaction to loud noises. 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, 75% of US ferrets with a blaze or white head sold from pet stores are deaf.^[10]
Domesticated cats with blue eyes and white coats are often completely deaf.^[11] Whether or not this is a result of Waardenburg syndrome remains unclear.^[12] Deafness is far more common in white cats than in those with other coat colors. According to the ASPCA Complete Guide to Cats, "17 to 20 percent of white cats with nonblue eyes are deaf; 40 percent of "odd-eyed" white cats with one blue eye are deaf; and 65 to 85 percent of blue-eyed white cats are deaf."^[13] In the 1980's, college genetic classes taught that the genes for deafness and white coat color were closely linked, resulting in the majority of cats with completely white coats and bluer eyes being deaf.^[14] The newer evidence cited above refutes this simplistic idea.

In popular culture[edit]

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.
The book Reconstructing Amelia by Kimberly McCreight features several characters with Waardenburg symptoms.

Other contributors[edit]

• 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[edit]

• Chediak–Higashi syndrome
• List of cutaneous conditions

References[edit]

1. ^ ^{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 totalis sive partialis, Albinismus circumscriptus (leucismus, poliosis) et Surditas congenita (surdimutitas)". Am. J. Hum. Genet. 3 (3): 195–253. PMC 1716407. PMID 14902764. 
2. ^ Petrus Johannes Waardenburg at Who Named It?
3. ^ Klein-Waardenburg syndrome at Who Named It?
4. ^ Arias S (1971). "Genetic Heterogeneity in the Waardenburg Syndrome". Birth Defects Original Article Series 7 (4): 87–101. PMID 5006208. 
5. ^ Kumar, Sudesh, and Kiran Rao. “Waardenburg Syndrome: A Rare Genetic Disorder, A Report of Two Cases.” Indian Journal of Human Genetics 18.2 (2012): 254-255. Academic Search Premier. Web. 4 Apr. 2014.,
6. ^ Egbalian F (2008). "Waardenburg-Shah Syndrome; A Case Report and Review of the Literature". Iranian Journal of Pediatrics 18 (1): 71–74. 
7. ^ "Premature Graying Of Hair". 
8. ^ Baral, Viviane, et al. “Screening of MTIF and SOX10 Regulatory Regions In Waardenburg Syndrome Type 2. “Plos ONE 7.7 (2012): 1-8. Academic Search Premier. Web. 4 Apr. 2014.
9. ^ Yang, T, et al. “Double Heterozygous Mutations Of MTIF and PAX3 Result in Waardenburg Syndrome With Increased Penetrance In Pigmentary defects.” Clinical Genetics 83.1 (2013): 78-62. Academic Search Premier. Web. 3 Apr. 2014.
10. ^ Matulich E. "Deafness in Ferrets". Cypresskeep.com. 
11. ^ Webb AA, Cullen CC (2010). "Coat color and coat color pattern-related neurologic and neuro-ophthalmic diseases". The Canadian Veterinary Journal 51 (6): 653–657. PMC 2871368. PMID 20808581. 
12. ^ Geigy CA, Heid S, Steffen F, Danielson K, Jaggy A, Gaillard C (2007). "Does a pleiotropic gene explain deafness and blue irises in white cats?". Veterinary Journal 173 (3): 548–553. doi:10.1016/j.tvjl.2006.07.021. PMID 16956778. 
13. ^ Richards J (1999). ASPCA Complete Guide to Cats: Everything You Need to Know About Choosing and Caring for Your Pet. Chronicle Books. p. 71. ISBN 9780811819299. 
14. ^ DeeAnn Williams Visk, personal recollection.

External links[edit]

• GeneReviews/NCBI/NIH/UW entry on Waardenburg Syndrome Type I
• OMIM Genetic disorder catalog — Waardenburg syndrome

v t e Inborn error of amino acid metabolism (E70–E72, 270) K→acetyl-CoA Lysine/straight chain Glutaric acidemia type 1 type 2 Hyperlysinemia Pipecolic acidemia Saccharopinuria Leucine 3-hydroxy-3-methylglutaryl-CoA lyase deficiency 3-Methylcrotonyl-CoA carboxylase deficiency 3-Methylglutaconic aciduria 1 Isovaleric acidemia Maple syrup urine disease Tryptophan Hypertryptophanemia G G→pyruvate→citrate Glycine D-Glyceric acidemia Glutathione synthetase deficiency Sarcosinemia Glycine→Creatine: GAMT deficiency Glycine encephalopathy G→glutamate→ α-ketoglutarate Histidine Carnosinemia Histidinemia Urocanic aciduria Proline Hyperprolinemia Prolidase deficiency Glutamate/glutamine SSADHD G→propionyl-CoA→ succinyl-CoA Valine Hypervalinemia Isobutyryl-CoA dehydrogenase deficiency Maple syrup urine disease Isoleucine 2-Methylbutyryl-CoA dehydrogenase deficiency Beta-ketothiolase deficiency Maple syrup urine disease Methionine Cystathioninuria Homocystinuria Hypermethioninemia General BC/OA Methylmalonic acidemia Methylmalonyl-CoA mutase deficiency Propionic acidemia G→fumarate Phenylalanine/tyrosine Phenylketonuria 6-Pyruvoyltetrahydropterin synthase deficiency Tetrahydrobiopterin deficiency Tyrosinemia Alkaptonuria/Ochronosis Type I tyrosinemia Type II tyrosinemia Type III tyrosinemia/Hawkinsinuria Tyrosine→Melanin Albinism: Ocular albinism (1) Oculocutaneous albinism (Hermansky–Pudlak syndrome) Waardenburg syndrome Tyrosine→Norepinephrine Dopamine beta hydroxylase deficiency reverse: Brunner syndrome G→oxaloacetate Urea cycle/Hyperammonemia (arginine aspartate) Argininemia Argininosuccinic aciduria Carbamoyl phosphate synthetase I deficiency Citrullinemia N-Acetylglutamate synthase deficiency Ornithine transcarbamylase deficiency/translocase deficiency Transport/ IE of RTT Solute carrier family: Cystinuria Hartnup disease Iminoglycinuria Lysinuric protein intolerance Fanconi syndrome: Oculocerebrorenal syndrome Cystinosis Other 2-Hydroxyglutaric aciduria Aminoacylase 1 deficiency Ethylmalonic encephalopathy Fumarase deficiency Trimethylaminuria Index of inborn errors of metabolism v t e Description Metabolism Enzymes and pathways: citric acid cycle enzymes glycolysis enzymes glycogenesis and glycogenolysis intermediates fructose and galactose intermediates pentose phosphate intermediates glycoproteins enzymes glycosaminoglycans proteoglycan enzymes lipid intermediates phospholipid metabolism cholesterol and steroid intermediates lipoprotein sphingolipids enzymes eicosanoids enzymes amino acid intermediates urea cycle enzymes heme and porphyrin intermediates metabolism nucleotide intermediates Disorders Citric acid cycle and electron transport chain Carbohydrate Glycoprotein Proteoglycan Fatty-acid Phospholipid Cholesterol and steroid Lipid Lipid storage Eicosanoid Amino acid Purine-pyrimidine Heme metabolism Symptoms and signs Treatment Drugs lipid-modifying other

v t e Pigmentation disorders/Dyschromia (L80–L81, 709.0) Hypo-/ leucism Loss of melanocytes vitiligo: Quadrichrome vitiligo Vitiligo ponctué syndromic Alezzandrini syndrome Vogt–Koyanagi–Harada syndrome melanocyte development: Piebaldism Waardenburg syndrome Tietz syndrome 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 Leukoderma w/o hypomelanosis Vasospastic macule Woronoff's ring Nevus anemicus 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 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 Linear Incontinentia pigmenti Scratch dermatitis Shiitake mushroom dermatitis Other/ungrouped Acanthosis nigricans Freckle Familial progressive hyperpigmentation Pallister–Killian syndrome Periorbital hyperpigmentation Photoleukomelanodermatitis of Kobori Postinflammatory hyperpigmentation Transient neonatal pustular melanosis 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 Dyschromatoses Dyschromatosis symmetrica hereditaria Dyschromatosis universalis hereditaria Index of skin v t e Description Anatomy Physiology Development Disease Infections Vesiculobullous Dermatitis and eczema Papulosquamous Urticaria and erythema Radiation-related Pigmentation Mucinoses Keratosis, ulcer, atrophy, and necrobiosis Vasculitis Fat Congenital Tumors nevi and melanomas epidermis dermis Symptoms and signs eponymous Treatment Procedures Drugs disinfectants emollients and protectives itch psoriasis other Wound and ulcer

v t e 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 (3) Helix-turn-helix domains 3.1 ARX Ohtahara syndrome Lissencephaly X2 MNX1 Currarino syndrome HOXD13 SPD1 Synpolydactyly PDX1 MODY 4 LMX1B Nail–patella syndrome MSX1 Tooth and nail syndrome OFC5 PITX2 Axenfeld syndrome 1 POU4F3 DFNA15 POU3F4 DFNX2 ZEB1 Posterior polymorphous corneal dystrophy Fuchs' dystrophy 3 ZEB2 Mowat–Wilson syndrome 3.2 PAX2 Papillorenal syndrome PAX3 Waardenburg syndrome 1&3 PAX4 MODY 9 PAX6 Gillespie syndrome Coloboma of optic nerve PAX8 Congenital hypothyroidism 2 PAX9 STHAG3 3.3 FOXC1 Axenfeld syndrome 3 Iridogoniodysgenesis, dominant type FOXC2 Lymphedema–distichiasis syndrome FOXE1 Bamforth–Lazarus syndrome FOXE3 Anterior segment mesenchymal dysgenesis FOXF1 ACD/MPV FOXI1 Enlarged vestibular aqueduct FOXL2 Premature ovarian failure 3 FOXP3 IPEX 3.5 IRF6 Van der Woude syndrome Popliteal pterygium syndrome (4) β-Scaffold factors with minor groove contacts 4.2 Hyperimmunoglobulin E syndrome 4.3 Holt–Oram syndrome Li–Fraumeni syndrome Ulnar–mammary syndrome 4.7 Campomelic dysplasia MODY 3 MODY 5 SF1 SRY XY gonadal dysgenesis Premature ovarian failure 7 SOX10 Waardenburg syndrome 4c Yemenite deaf-blind hypopigmentation syndrome 4.11 Cleidocranial dysostosis (0) Other transcription factors 0.6 Kabuki syndrome Ungrouped TCF4 Pitt–Hopkins syndrome ZFP57 TNDM1 TP63 Rapp–Hodgkin syndrome/Hay–Wells syndrome/Ectrodactyly–ectodermal dysplasia–cleft syndrome 3/Limb–mammary syndrome/OFC8 Transcription coregulators Coactivator: CREBBP Rubinstein–Taybi syndrome Corepressor: HR (Atrichia with papular lesions) See also transcription factors and intracellular receptors B structural perx skel cili mito nucl sclr DNA/RNA/protein synthesis drep trfc tscr tltn membrane icha slcr atpa abct othr transduction iter csrc itra trfk

v t e 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 Müllerian 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) 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 drep trfc tscr tltn membrane icha slcr atpa abct othr transduction iter csrc itra trfk

v t e Extracellular ligand disorders Cytokine EDA Hypohidrotic ectodermal dysplasia Camurati-Engelmann disease Ephrin Craniofrontonasal dysplasia WNT Tetra-amelia syndrome TGF OFC 11 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 drep trfc tscr tltn membrane icha slcr atpa abct othr transduction iter csrc itra trfk