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BMC Medical Genetics
Published in: BMC Medical Genetics 1/2018

Open Access 01-12-2018 | Case report

FLNA mutations in surviving males presenting with connective tissue findings: two new case reports and review of the literature

Authors: Elyssa Cannaerts, Anju Shukla, Mensuda Hasanhodzic, Maaike Alaerts, Dorien Schepers, Lut Van Laer, Katta M. Girisha, Iva Hojsak, Bart Loeys, Aline Verstraeten

Published in: BMC Medical Genetics | Issue 1/2018

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Abstract

Background

Mutations in the X-linked gene filamin A (FLNA), encoding the actin-binding protein FLNA, cause a wide spectrum of connective tissue, skeletal, cardiovascular and/or gastrointestinal manifestations. Males are typically more severely affected than females with common pre- or perinatal death.

Case presentation

We provide a genotype- and phenotype-oriented literature overview of FLNA hemizygous mutations and report on two live-born male FLNA mutation carriers. Firstly, we identified a de novo, missense mutation (c.238C > G, p.(Leu80Val)) in a five-year old Indian boy who presented with periventricular nodular heterotopia, increased skin laxity, joint hypermobility, mitral valve prolapse with regurgitation and marked facial features (e.g. a flat face, orbital fullness, upslanting palpebral fissures and low-set ears). Secondly, we identified two cis-located FLNA mutations (c.7921C > G, p.(Pro2641Ala); c.7923delC, p.(Tyr2642Thrfs*63)) in a Bosnian patient with Ehlers-Danlos syndrome-like features such as skin translucency and joint hypermobility. This patient also presented with brain anomalies, pectus excavatum, mitral valve prolapse, pulmonary hypertension and dilatation of the pulmonary arteries. He died from heart failure in his second year of life.

Conclusions

These two new cases expand the list of live-born FLNA mutation-positive males with connective tissue disease from eight to ten, contributing to a better knowledge of the genetic and phenotypic spectrum of FLNA-related disease.
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Metadata
Title
FLNA mutations in surviving males presenting with connective tissue findings: two new case reports and review of the literature
Authors
Elyssa Cannaerts
Anju Shukla
Mensuda Hasanhodzic
Maaike Alaerts
Dorien Schepers
Lut Van Laer
Katta M. Girisha
Iva Hojsak
Bart Loeys
Aline Verstraeten
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2018
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/s12881-018-0655-0

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