Expansion of the variable expression of Muenke syndrome: Hydrocephalus without craniosynostosis.

Muenke syndrome (MS) is an autosomal dominant coronal craniosynostosis syndrome with variable extracranial anomalies. We studied 56 unrelated patients with non-syndromic uni- or bicoronal craniosynostosi to identify the frequency and clinical characteristics of MS in a cohort of Mexican childrens. The FGFR3 pathogenic variation p.Pro250Arg responsible for MS was characterized in all probands by PCR-restriction assay; available first-degree relatives (15 parents, 5 siblings) of the confirmed p.Pro250Arg carriers were also tested. All heterozygotes for p.Pro250Arg underwent clinical and audiologic assessment, as well as X-ray evaluations of hands and feet. Eight of 56 probands (14%) were found to carry the p.Pro250Arg variant and half of them were familial cases. Four p.Pro250Arg heterozygous familial members had been considered unaffected before the molecular testing. In one MS family, hydrocephalus without craniosynostosis, was documented as the only clinical manifestation in a previously undetected heterozygous male sibling. Hydrocephalus without craniosynostosis in a patient with the p.Pro250Arg variant suggests that some patients with MS might present only this manifestation; to our knowledge, hydrocephalus has not been described as isolated feature in MS, so we propose to consider this feature as an expansion of the MS phenotype rather than an unrelated finding. Our data also reinforce the notion that molecular testing of FGFR3 must be included in the diagnostic approach of coronal craniosynostosis. This will allow accurate genetic counseling and optimal management of MS, which might otherwise go undiagnosed because of mild manifestations and wide variability of expression. © 2016 Wiley Periodicals, Inc.

Unique spectrum of GJB2 mutations in Mexico.

OBJECTIVE: The aim of this study was to elucidate the involvement of mutations in three relatively common deafness genes in Mexican individuals with non-syndromic hearing loss. METHODS: We sequenced GJB2 for mutations, screened for two deletions involving GJB6, del(GJB6-D13S1830) and del(GJB6-D13S1854), and for the m.1555A>G mutation in the MTRNR1 gene in 76 (71 simplex and 5 multiplex) unrelated Mexican probands with prelingual non-syndromic hearing loss. Samples were obtained from the Department of Genetics at Instituto Nacional de Rehabilitacion in Mexico City. RESULTS: Eight previously reported pathogenic variants and two polymorphic variants in GJB2 were identified. The two screened GJB6 deletions and the m.1555A>G mutation were not detected. Eight cases (10.6%) were found to have bi-allelic mutations in GJB2 and six (7.9%) were found to have a monoallelic GJB2 mutation. Of the six monoallelic mutations, one (p.R184Q) was a previously reported autosomal dominant variant. The most frequent pathological allele detected in this population was the c.35delG mutation in the GJB2 gene. The p.V27I polymorphic variant was also detected, with an allele frequency of 0.24. All eight probands with GJB2 mutations had symmetric profound deafness, whereas patients without GJB2 mutations had moderate, severe or profound hearing loss. CONCLUSIONS: This study shows that GJB2 mutations are an important cause of prelingual deafness in the Mexican population.

[Sjögren's syndrome: Audiological and clinical behaviour in terms of age]. / Síndrome de Sjögren comportamiento clínico y audiológico en función de la edad.

INTRODUCTION AND OBJECTIVE: To determine the clinical and audiological behaviour per age group in Sjögren's Syndrome (SS), considering that it is the second most frequent autoimmune rheumatic disease. MATERIAL AND METHOD: The study included 29 patients with SS with clinical history and audiological studies. The design was prospective, descriptive and transversal. RESULTS: Average patient age was 41 years. All the patients with hearing loss in conventional tone audiometry were of the sensory type. At high frequencies, 66% of the patients did not respond at 20 KHz, and 48% at the frequency of 16 KHz. In logoaudiometry and impedancemetry, the results were the ones expected for the auditory thresholds. CONCLUSIONS: Auditory damage related to SS is located in the inner ear. Patients must be informed by their physician of the risk of having auditory damage as a complication of the disease. Audiological evaluation must be performed periodically to identify possible audiological damage.