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Waardenburg-Shah syndrome

MedGen UID:: 979427
•Concept ID:: CN296453
•: Disease or Syndrome

Synonyms:	Waardenburg syndrome, type 4; Waardenburg-Hirschsprung disease
Modes of inheritance:	Autosomal recessive inheritance MedGen UID: 141025 •Concept ID: C0441748 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Autosomal dominant inheritance MedGen UID: 141047 •Concept ID: C0443147 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Autosomal recessive inheritance (Orphanet) Autosomal dominant inheritance (Orphanet)

Related genes: Gene(s) associated with related conditions. For conditions in a hierarchy, the parent condition will list the genes associated with the children conditions.	SOX10, EDNRB, EDN3

Monarch Initiative:	MONDO:0019518
Orphanet:	ORPHA897

Definition

Waardenburg-Shah syndrome (WSS), also known as Waardenburg syndrome type 4 (WS4) is characterized by the association of Waardenburg syndrome (sensorineural hearing loss and pigmentary abnormalities) and Hirschsprung disease (aganglionic megacolon). [from ORDO]

Term Hierarchy

GTR
MeSH

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVWaardenburg-Shah syndrome

Phenotypic abnormality
- Abnormality of the integument
  - Abnormality of the skin
    - Abnormal skin morphology
      - Abnormality of skin pigmentation
        Hypopigmentation of the skin
        Waardenburg-Shah syndrome
        Waardenburg syndrome type 4A
        Waardenburg syndrome type 4B
        Waardenburg syndrome type 4C

Recent clinical studies

Etiology

The SOXE transcription factors-SOX8, SOX9 and SOX10-share a bi-partite transactivation mechanism.

Haseeb A, Lefebvre V
Nucleic Acids Res 2019 Jul 26;47(13):6917-6931. doi: 10.1093/nar/gkz523. PMID: 31194875 Free PMC Article

Analysis of SOX10 mutations identified in Waardenburg-Hirschsprung patients: Differential effects on target gene regulation.

Chan KK, Wong CK, Lui VC, Tam PK, Sham MH
J Cell Biochem 2003 Oct 15;90(3):573-85. doi: 10.1002/jcb.10656. PMID: 14523991

The importance of having your SOX on: role of SOX10 in the development of neural crest-derived melanocytes and glia.

Mollaaghababa R, Pavan WJ
Oncogene 2003 May 19;22(20):3024-34. doi: 10.1038/sj.onc.1206442. PMID: 12789277

Cloning and characterisation of the Sry-related transcription factor gene Sox8.

Schepers GE, Bullejos M, Hosking BM, Koopman P
Nucleic Acids Res 2000 Mar 15;28(6):1473-80. doi: 10.1093/nar/28.6.1473. PMID: 10684944 Free PMC Article

SOX10 mutations in patients with Waardenburg-Hirschsprung disease.

Pingault V, Bondurand N, Kuhlbrodt K, Goerich DE, Préhu MO, Puliti A, Herbarth B, Hermans-Borgmeyer I, Legius E, Matthijs G, Amiel J, Lyonnet S, Ceccherini I, Romeo G, Smith JC, Read AP, Wegner M, Goossens M
Nat Genet 1998 Feb;18(2):171-3. doi: 10.1038/ng0298-171. PMID: 9462749

See all (9)

Diagnosis

Neurological Waardenburg-Shah syndrome: a diagnostic challenge in a child with skin hypopigmentation and neurological manifestation.

Ng BW, Lee JS, Toh TH, Ngu LH
BMJ Case Rep 2022 Jun 20;15(6) doi: 10.1136/bcr-2022-250360. PMID: 35725288 Free PMC Article

The additional genetic diagnosis of homozygous sickle cell disease in a patient with Waardenburg-Shah syndrome: a case report.

Rankine-Mullings AE, Serjeant G, Ramsay Z, Hanchard NA, Asnani M
J Med Case Rep 2019 Jan 13;13(1):10. doi: 10.1186/s13256-018-1953-z. PMID: 30636638 Free PMC Article

Waardenburg-Shah Syndrome: a rare case in an Indian child.

Pattebahadur R, Singhi S, Maharana PK
BMJ Case Rep 2016 Sep 30;2016 doi: 10.1136/bcr-2016-216366. PMID: 27694333 Free PMC Article

Shah-Waardenburg syndrome.

Mahmoudi A, Rami M, Khattala K, Elmadi A, Afifi MA, Youssef B
Pan Afr Med J 2013;14:60. Epub 2013 Feb 12 doi: 10.11604/pamj.2013.14.60.1543. PMID: 23565307 Free PMC Article

Clinical variability of Waardenburg-Shah syndrome in patients with proximal 13q deletion syndrome including the endothelin-B receptor locus.

Tüysüz B, Collin A, Arapoğlu M, Suyugül N
Am J Med Genet A 2009 Oct;149A(10):2290-5. doi: 10.1002/ajmg.a.33031. PMID: 19764031

See all (9)

Prognosis

The SOXE transcription factors-SOX8, SOX9 and SOX10-share a bi-partite transactivation mechanism.

Haseeb A, Lefebvre V
Nucleic Acids Res 2019 Jul 26;47(13):6917-6931. doi: 10.1093/nar/gkz523. PMID: 31194875 Free PMC Article

The additional genetic diagnosis of homozygous sickle cell disease in a patient with Waardenburg-Shah syndrome: a case report.

Rankine-Mullings AE, Serjeant G, Ramsay Z, Hanchard NA, Asnani M
J Med Case Rep 2019 Jan 13;13(1):10. doi: 10.1186/s13256-018-1953-z. PMID: 30636638 Free PMC Article

Shah-Waardenburg syndrome.

Mahmoudi A, Rami M, Khattala K, Elmadi A, Afifi MA, Youssef B
Pan Afr Med J 2013;14:60. Epub 2013 Feb 12 doi: 10.11604/pamj.2013.14.60.1543. PMID: 23565307 Free PMC Article

Waardenburg syndrome with extended aganglionosis: report of 3 new cases.

Karaca I, Turk E, Ortac R, Kandirici A
J Pediatr Surg 2009 Jun;44(6):E9-13. doi: 10.1016/j.jpedsurg.2009.02.057. PMID: 19524716

Near-total intestinal aganglionosis in the Waardenburg-Shah syndrome.

Shim WK, Derieg M, Powell BR, Hsia YE
J Pediatr Surg 1999 Dec;34(12):1853-5. doi: 10.1016/s0022-3468(99)90330-5. PMID: 10626872

See all (7)

Clinical prediction guides

The SOXE transcription factors-SOX8, SOX9 and SOX10-share a bi-partite transactivation mechanism.

Haseeb A, Lefebvre V
Nucleic Acids Res 2019 Jul 26;47(13):6917-6931. doi: 10.1093/nar/gkz523. PMID: 31194875 Free PMC Article

Genetic Analyses of a Three Generation Family Segregating Hirschsprung Disease and Iris Heterochromia.

Cui L, Wong EH, Cheng G, Firmato de Almeida M, So MT, Sham PC, Cherny SS, Tam PK, Garcia-Barceló MM
PLoS One 2013;8(6):e66631. Epub 2013 Jun 26 doi: 10.1371/journal.pone.0066631. PMID: 23840513 Free PMC Article

The role of SOX10 during enteric nervous system development.

Bondurand N, Sham MH
Dev Biol 2013 Oct 1;382(1):330-43. Epub 2013 May 2 doi: 10.1016/j.ydbio.2013.04.024. PMID: 23644063

Novel mutations of endothelin-B receptor gene in Pakistani patients with Waardenburg syndrome.

Jabeen R, Babar ME, Ahmad J, Awan AR
Mol Biol Rep 2012 Jan;39(1):785-8. Epub 2011 May 6 doi: 10.1007/s11033-011-0799-x. PMID: 21547364

The importance of having your SOX on: role of SOX10 in the development of neural crest-derived melanocytes and glia.

Mollaaghababa R, Pavan WJ
Oncogene 2003 May 19;22(20):3024-34. doi: 10.1038/sj.onc.1206442. PMID: 12789277

See all (9)