A case of Beare–Stevenson syndrome with a broad spectrum of features and a review of the FGFR2 Y375C mutation phenotype

Abstract

We present a case of Beare-Stevenson syndrome with a broad range of phenotypic features including craniosynostosis, cutis gyrata, choanal stenosis, bifid scrotum with perineal hypospadias and a caudal appendage. The paternal age at the time of conception was 62 years consistent with a paternal age effect. Mutation analysis was undertaken and demonstrated the FGFR2 Y375C mutation. This case, one of only nine with molecular analysis, confirms the significant morbidity associated with this syndrome.

Hearing loss in syndromic craniosynostoses: Otologic manifestations and clinical findings

“…Commonly described ear malformations included posteriorly angulated ears, stenotic auditory canals, preauricular furrows, and narrow ear canals (Table 3) [40,69]. To date, one patient has been reported with hearing loss, which was severe bilateral conductive hearing loss [64]. This patient had skin pitting of the bilateral ears.…”

“…A summation of all audiological series of Beare Stevenson syndrome reveals hearing loss in 1/26 patients (4%). Of these 26 patients reported to date, 24 have descriptions of the physical examination of the ear [40,61,62,[64][65][66][67][68][69][70][71][72][73][74][75][76][77][78]. Of these 24 patients, only one patient was not described as having ear malformations.…”

Atypical Skin Manifestations in <b><i>FGFR2</i></b>-Related Craniosynostosis Syndromes Broaden the Phenotypic Spectrum

“…Cutis gyrata, acanthosis nigricans, skin furrows, skin tags, and deep palmar and plantar creases are usual [Przylepa et al, 1996;Akai et al, 2002;Vargas et al, 2003;McGaughran et al, 2006;Slavotinek et al, 2009;Robin et al, 2011]. The mechanisms by which cutis gyrata and acanthosis nigricans are caused by the FGFR 2 mutations remain unclear.…”

Beare-Stevenson cutis gyrata syndrome: A new case of a c.1124C↷G (Y375C) mutation in the FGFR2 gene

“…Two cases harbored a c.1115C¡G transversion (9,14) located in the carboxyl-terminal end of the linker region between the immunoglobulin III-like (Iglll) and transmembrane domains of the protein, and 9 cases harbored a c.1124A¡G transition (4,(8)(9)(10)(11)(12)(13) located in the transmembrane region of the protein. In 2 patients, no FGFR2 mutations were detected, suggesting further genetic heterogeneity (9).…”

“…These symptoms overlap with other disorders, such as Crouzon syndrome; however, the prognosis for BSS is worse than in these other disorders (6). BSS cases are sporadic, and a paternal age effect has been suggested (4,7,8). Molecular analysis of BSS cases has revealed two closely spaced mutations in exon 11 of the FGFR2 gene: c.1115C¡G (S372C) in 2 patients and c.1124C¡G (Y375C) in 9 patients (4,6,(8)(9)(10)(11)(12)(13)(14).…”