(Klein-Waardenburg syndrome, Waardenburg-Shah syndrome)

Rare.  Auditory-pigmentary syndrome due to a neural crest migration disorder resulting in an absence of melanocytes in the skin, hair, eyes and inner ear.

At least 4 types have been described

-        I or WS1 [MIM 193 500]: variable-penetrance autosomal dominant transmission of a mutation in the PAX3 gene (2q36.1): pigmentation anomalies: white hair strands (from birth), white eyelashes/brows, iris heterochromia (or sapphire-blue eyes), sensorineural deafness, dystopia canthi.

-        IIa or WS2A [MIM 193 510]: variable-penetrance autosomal dominant transmission of a mutation in the MITF gene (3p13): type I but no dystopia canthi, sometimes ocular albinism.

-        IIb or WS2B [MIM 600 193]: autosomal dominant transmission with variable penetrance of a mutation in the WSS2B gene (1p21-p13.3).

-        IIc or WS2C [MIM 606 662]: mutation of the WS2C gene (8p23)

-        IId or WS2D: deletion of the SNAI2 gene (8q11): variant of unknown significance

-        IIE or WS2E [MIM 611 584]: variable-penetrance autosomal dominant transmission of a mutation in the SOX10 gene (22q13); type I with or without neurological abnormalities, hypogonadotrophic hypogonadism

-        IIF or WS2F [MIM 619 947]: autosomal recessive transmission of a mutation in the KITLG gene (12q21)

-        III: Waardenburg-Klein syndrome [MIM 148,820]: variable-penetrance autosomal recessive or dominant transmission of a mutation in the PAX3 gene (2q36.1): like type I, with upper-limb anomalies (syndactyly, carpal fusion, scapula elevation).

-        IV: Waardenburg-Shah syndrome: autosomal recessive transmission of a mutation in the EDNRB gene (13q22.3) (WS4A, [MIM 277 580]), or EDN3 (20q13.32) (WSAB, [MIM 613 265]) or variable-penetrance dominant transmission of a mutation in SOX10 at 22q13.1 (WAS4C, [MIM 613 266]): type I associated with often extensive Hirschsprung's disease

-        IV plus or Waardenburg-Shah demyelinating form or PCWH syndrome (acronym for Peripheral demyelinating neuropathy, Central dysmyelination, Waardenburg syndrome, and Hirschsprung disease ) [MIM 609 136]: like type IV due to a mutation in the SOX10 gene, but central and peripheral neurological involvement is present: neonatal hypotonia, intellectual deficit of variable severity, nystagmus, progressive spasticity, ataxia and epilepsy, sometimes signs of dysautonomia (alacrymia, bradycardia)

Clinical diagnosis :

Major criteria :

-        synophris: hair implantation in the brow area

-        sensorineural deafness (30-50 %) of variable severity

-        canthal dystopia (dystopia canthi): medial canthus of each eye displaced laterally

-        heterochromia: wall or heterochromic eyes or sapphire-blue irises

-        pigmentation abnormalities: white hair strands (from birth), white eyelashes/brow or early hair whitening before age 20.

-        family history

Minor criteria :

-        skin pigmentation anomalies (patches of vitiligo, congenital leukoderma)

-         wide nasal root or hypoplasia of the nasal wings

Occasionally :

-        cleft lip or palate

-        congenital elevation of the scapula

-        spina bifida, scoliosis

-        cardiac malformation (CIA)

Anesthetic implications:

according to the mode of presentation and the associated abnormalities.

References:

-        Kfoury T, Staiti G, Baujard C, Benhamou D.
Pudendal nerve block by nerve stimulation in a child with Waardenburg disease.
Pediatr Anesth 2008; 18: 1267-8

-        Saha RP, Bhusalb A, Tek Yogic TN, Niraulac R, Suraj KC, Yadavb SK.
Waardenburg syndrome and Hirschsprung disease in a child: a case report.
J Pediatr Surgery Case Reports 2024 ; 101 : 102770, doi.org/10.1016/j.epsc.2023.102770

Updated: June 2024