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Frontometaphyseal dysplasia and keloid formation without FLNA mutations
Author(s) -
Basart Hanneke,
van de Kar Annekatrien,
Adès Lesley,
Cho TaeJoon,
Carter Erin,
Maas Saskia M.,
Wilson Louise C.,
van der Horst Chantal M. A. M.,
Wade Emma M.,
Robertson Stephen P.,
Hennekam Raoul C.
Publication year - 2015
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.37044
Subject(s) - flna , dysplasia , etiology , medicine , genetics , keloid , foreskin , stenosis , mutation , pathology , filamin , biology , gene , cytoskeleton , cell , cell culture
Frontometaphyseal dysplasia (FMD) is a distinctive sclerosing skeletal dysplasia associated with a number of non‐skeletal manifestations including hearing loss, cardiac malformations, and stenosis, particularly of the upper airway and urinary tract. Some, but not all, patients have mutations in FLNA causing the condition. Consonant with the X chromosomal location of FLNA males are generally more severely affected than females. FLNA mutations can be detected in 82% of affected males. We describe seven patients (one male, six females) all of whom have the major clinical and radiological features of FMD, but without detectable mutations in FLNA . The females in our cohort are affected to a similar degree as is usually found in males. In addition, all patients have marked keloid formation at various body sites, including the eye, from an early age. Other features that may indicate a different etiology in these patients are the increased frequency of cleft palate, Robin sequence, tracheal stenosis, and mild intellectual disability, which all occur in three of more patients in the present group. All patients are isolated. We hypothesize that the presently reported patients represent further evidence that phenotypes strongly resembling FMD exist that are not accounted for by mutations in FLNA . Since the frequency of several of the manifestations, their sporadic presentations, and the presence of keloid formation differ from the X‐linked form of this condition we propose de novo autosomal dominant acting mutations in a gene functionally related to FLNA , underpin this disorder. © 2015 Wiley Periodicals, Inc.