Waardenburg syndrome: a rare cause of inherited neuropathy due to SOX10 mutation.

Waardenburg syndrome (WS) is a rare disorder comprising sensorineural deafness and pigmentation abnormalities. Four distinct subtypes are defined based on the presence or absence of additional symptoms. Mutations in six genes have been described in WS. SOX10 mutations are usually associated with a more severe phenotype of WS with peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, and Hirschsprung disease. Here we report a 32-year-old man with a novel heterozygous missense variant in SOX10 gene, who presented with congenital deafness, Hirschsprung disease, iris heterochromia, foot deformity, and intermediate conduction velocity length-dependent sensorimotor neuropathy. This case highlights that the presence of other non-neuropathic features in a patient with presumed hereditary neuropathy should alert the clinician to possible atypical rare causes.

Chronic constipation recognized as a sign of a SOX10 mutation in a patient with Waardenburg syndrome.

Waardenburg syndrome is characterized by hearing loss, pigmentation abnormalities, dysmorphologic features, and neurological phenotypes. Waardenburg syndrome consists of four distinct subtypes, and SOX10 mutations have been identified in type II and type IV. Type IV differs from type II owing to the presence of Hirschsprung disease. We identified a de novo nonsense mutation in SOX10 (p.G39X) in a female pediatric patient with Waardenburg syndrome with heterochromia iridis, profound bilateral sensorineural hearing loss, inner ear malformations, and overall hypopigmentation of the hair without dystopia canthorum. This patient has experienced chronic constipation since she was a neonate, but anorectal manometry showed a normal anorectal reflex. Chronic constipation in this patient was likely to be a consequence of a mild intestinal disorder owing to the SOX10 mutation, and this patient was considered to have a clinical phenotype intermediate between type II and type IV of the syndrome. Chronic constipation may be recognized as indicative of a SOX10 mutation in patients with Waardenburg syndrome.

Spectrum of temporal bone abnormalities in patients with Waardenburg syndrome and SOX10 mutations.

BACKGROUND AND PURPOSE: Waardenburg syndrome, characterized by deafness and pigmentation abnormalities, is clinically and genetically heterogeneous, consisting of 4 distinct subtypes and involving several genes. SOX10 mutations have been found both in types 2 and 4 Waardenburg syndrome and neurologic variants. The purpose of this study was to evaluate both the full spectrum and relative frequencies of inner ear malformations in these patients. MATERIALS AND METHODS: Fifteen patients with Waardenburg syndrome and different SOX10 mutations were studied retrospectively. Imaging was performed between February 2000 and March 2010 for cochlear implant work-up, diagnosis of hearing loss, and/or evaluation of neurologic impairment. Eleven patients had both CT and MR imaging examinations, 3 had MR imaging only, and 1 had CT only. RESULTS: Temporal bone abnormalities were bilateral. The most frequent pattern associated agenesis or hypoplasia of ≥1 semicircular canal, an enlarged vestibule, and a cochlea with a reduced size and occasionally an abnormal shape, but with normal partition in the 13/15 cases that could be analyzed. Three patients lacked a cochlear nerve, bilaterally in 2 patients. In addition, associated abnormalities were found when adequate MR imaging sequences were available: agenesis of the olfactory bulbs (7/8), hypoplastic or absent lacrimal glands (11/14), hypoplastic parotid glands (12/14), and white matter signal anomalies (7/13). CONCLUSIONS: In the appropriate clinical context, bilateral agenesis or hypoplasia of the semicircular canals or both, associated with an enlarged vestibule and a cochlear deformity, strongly suggests a diagnosis of Waardenburg syndrome linked to a SOX10 mutation.

Shah-Waardenburg syndrome and PCWH associated with SOX10 mutations: a case report and review of the literature.

Shah-Waardenburg syndrome is a rare congenital disorder with variable clinical expression, characterised by aganglionosis of the rectosigmoïd (Hirschsprung disease), and abnormal melanocyte migration, resulting in pigmentary abnormalities and sensorineural deafness (Waardenburg syndrome). Mutations in the EDN, EDNRB and SOX10 genes can be found in patients with this syndrome. SOX10 mutations are specifically associated with a more severe phenotype called PCWH: peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease. Neuronal expression of SOX10 occurs in neural crest cells during early embryonic development and in glial cells of the peripheral and central nervous systems during late embryonic development and in adults. We present a 4-year-old girl with the PCWH phenotype associated with a de novo nonsense mutation (S384X) in SOX10. Main clinical features were mental retardation, peripheral neuropathy, deafness, Hirschsprung disease, distal arthrogryposis, white hairlock, and growth retardation. She presented with hypotonia, developmental delay, reduced peripheral nerve conduction velocities, and radiologically assessed central hypomyelination. Subsequently, the formation of abnormal myelin within the central and peripheral nervous system was functionally and radiologically assessed. Children presenting with features of Waardenburg syndrome and neurological dysfunction should be tested for mutations in the SOX10 gene to enable diagnosis and counselling.

A case report of prenatally diagnosed ophthalmo-acromelic syndrome type Waardenburg.

Ophthalmo-acromelic syndrome type Waardenburg is an extremely rare autosomal recessive syndrome comprising eye malformations ranging from true anophthalmia to mild microphthalmia with acromelic malformations. We report a case of ophthalmo-acromelic syndrome type Waardenburg diagnosed prenatally.

Temporal bone imaging findings in Waardenburg's syndrome.

OBJECTIVE: (a) To report computed tomography findings of eight new cases with Waardenburg's syndrome (WS) type I and review reported temporal bone radiographic and histopathological findings in WS with hearing loss; (b) To determine the frequency of inner ear pathologies that may contraindicate cochlear implantation. METHODS: A review of 1166 pediatric patients with sensorineural hearing loss revealed 12 cases (1%) with WS, whose family screenings disclosed additional 12 subjects with the same disorder. Among these 24 cases, eight had WS type I and were subjected to computed tomography scanning of temporal bone. Imaging findings of 28 cases reported previously in English literature were evaluated together with our eight patients. RESULTS: Malformation of the inner ear was found in none of the nine WS type I cases evaluated here, while the frequency of internal acoustic canal malformation was 11%. Regardless of the subtypes of the syndrome, 6 of 36 cases (17%) had radiological abnormality of the inner ear. Malformation and/or absence of the semicircular canals were the most common congenital abnormality of the inner ear. Hypoplasia of the cochlea was present in 3 of 36 cases (8%). CONCLUSIONS: Abnormality of bony labyrinth in WS with congenital deafness is not a frequent finding, particularly in WS type I. Therefore, the otologist and audiologist must keep in mind that most of these cases are suitable for cochlear implantation regarding inner ear anatomy.

Ophthalmo-acromelic syndrome: report and review.

The ophthalmo-acromelic syndrome of Waardenburg is an autosomal recessive trait comprising eye malformations ranging from true anophthalmia to mild microphthalmia with acromelic malformations. Some 29 affected individuals have been reported since Waardenburg's first report in 1935 [Waardenburg et al., 1961]. We report on a new case with bilateral anophthalmia and typical limb malformations. The patient also was found to have interruption of the inferior vena cava with azygos continuation as an additional finding. The previous reports are reviewed to elucidate the spectrum of the syndrome.

Partial anodontia in a case of Waardenburg's syndrome.

On routine examination of a case of Waardenburg's syndrome apart from the usual features of the disorder, partial anodontia involving both the lower lateral incisors was evident. The interesting association of partial anodontia and Waardenburg's syndrome is discussed along with relevant available literature.

Anophthalmia-Waardenburg syndrome: a report of three cases.

We report on 2 Turkish families with children who had bilateral anophthalmia, upper and lower limb abnormalities, mental retardation and consanguineous parents. We have evaluated the 2 cases in the first family and the only case in the second as anophthalmia-Waardenburg syndrome. This is an extremely rare autosomal recessive syndrome.

Anophthalmos-syndactyly (Waardenburg) syndrome without oligodactyly of toes.

We report on 2 brothers from a consanguineous family from a small city of southeast Turkey. Both have bilateral anophthalmia, soft tissue syndactyly of the feet, bilateral partial synostosis of metatarsals IV and V, and basal synostosis of the fourth and fifth toes on the right in the older sib only, thus differing from all previously reported cases of anophthalmos-syndactyly syndrome.

Aplasia of posterior semicircular canal in Waardenburg syndrome type II.

A case of Waardenburg syndrome type II is reported. The computed tomography (CT) revealed aplasia of the posterior semicircular canal and poor development of the vestible. Until now, including our case, only a few cases of Waardenburg syndrome with deafness were studied roentgenologically. Among them, at least 26% revealed aplasia of the posterior semicircular canal, which infers that it is a characteristic finding of Waardenburg syndrome.

[CT findings of the temporal bones in Waardenburg's syndrome].

We reported three cases of Waardenburg's syndrome and discussed CT findings of the temporal bones. Two cases of these patients were mother and daughter. Case 1, a two-year-old girl, had lateral displacement of the medial canthi, a broad nasal root, hetero-chromic iridis, left ptosis, albinotic fundus, and bilateral congenital deafness. CT findings of the temporal bones showed enlarged vestibules, short lateral semicircular canal, and absent right posterior semicircular canal. The mother had congenital deafness, heterochromia iridis, and a white forelock and showed similar abnormal CT findings of the temporal bones. Case 2, a one-year-old boy, had lateral displacement of the medial canthi, a broad nasal root, partial heterochromia iridis, albinotic fundus, and bilateral congenital deafness. CT findings of the temporal bones showed enlarged vestibules and absence of semicircular canals except the right lateral semicircular canal. These cases were diagnosed as Waardenburg's syndrome on the basis of the characteristic features.

Tomographic findings of the inner ears of 24 patients with Waardenburg's syndrome.

The tomographic findings in the Stenvers' projection of inner ears of 24 patients with Waardenburg's syndrome are described. In 12 of these 48 inner ears deafness was found. The roentgenographic examination did not show any malformation of the inner ears of these patients. In the literature on this subject, the tomographic findings of the inner ears of 12 deaf patients with Waardenburg's syndrome have been described. In 8 of them malformations were reported, especially of the semicircular canals. These findings in the literature could not be confirmed by our study.