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.