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Peripheral demyelinating neuropathy-central dysmyelinating leukodystrophy-Waardenburg syndrome-Hirschsprung disease
Waardenburg-Shah syndrome, neurologic variant, also referred to as Peripheral demyelinating neuropathy, Central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease (PCWH), is characterized by the association of the features of WSS (sensorineural hearing loss, pigmentary abnormalities and Hirschsprung disease; see this term) with neurological features, namely, neonatal hypotonia, intellectual deficit (of variable severity), nystagmus, progressive spasticity, ataxia and epilepsy.
- Neurologic Waardenburg-Shah syndrome
- WS4 plus
- Prevalence: <1 / 1 000 000
- Inheritance: Autosomal dominant
- Age of onset: Infancy, Neonatal
- ICD-10: E75.2
- OMIM: 609136
- UMLS: C1836727
- MeSH: -
- GARD: -
- MedDRA: -
Prevalence is unknown but less than 30 cases have been reported in the literature so far.
Autonomic dysfunction (reduced saliva production, sweating and tearing, and bradycardia and arrhythmia) may also be present. Delayed white matter myelination is present on brain MRI, and may also be responsible for neuropathy at the peripheral level. Hirschsprung disease is sometimes absent.
Most of the cases are caused by mutations involving the SOX10 gene (22q13.1): either a large deletion or point mutation located in the last two exons.
Most cases are sporadic but a few patients with an affected sibling have been reported and are associated with germinal mosaicism in one of the parents.
Management and treatment
In addition to management of the WSS and neurologic manifestations, cardiac examination and follow-up is recommended since these patients should be considered as at risk of arrhythmia. T
he prognosis and disease course may be severe with onset of deafness, intellectual deficit and sometimes motor impairment. Early death (shortly after birth) has been reported in some cases. Long-term evolution in adulthood is not well established.
- Review article
- English (2014)