Two Patients with Severe Short Stature due to a FBN1 Mutation (p.Ala1728Val) with a Mild Form of Acromicric Dysplasia
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Citações na Scopus
21
Tipo de produção
article
Data de publicação
2016
Título da Revista
ISSN da Revista
Título do Volume
Editora
KARGER
Autores
BRUIN, Christiaan de
FINLAYSON, Courtney
ANDREW, Melissa
HWA, Vivian
DAUBER, Andrew
Citação
HORMONE RESEARCH IN PAEDIATRICS, v.86, n.5, p.342-348, 2016
Resumo
Background: Acromicric dysplasia (AD) and geleophysic dysplasia 2 (GD2) belong to the category of acromelic dysplasia syndromes, consisting of severe short stature, short hands and feet and skin thickening. Both can result from missense mutations in the transforming growth factor beta 5 domain of the fibrillin-1 gene (FBN1). Methods: Two patients (P1 age 10, and P2 age 7) from unrelated families presented to their endocrinologist with severe short stature (approx.-4 SDS). They were otherwise asymptomatic and only had mild facial dysmorphisms. Extensive endocrine work-up did not reveal an underlying etiology. Exome sequencing was performed in each family. Results: Exome sequencing identified the presence of the same heterozygous missense variant c.C5183T (p.Ala1728Val) in the FBN1 gene in both P1 and P2. This variant was previously reported in a patient with GD2 and associated cardiac valvulopathy and hepatomegaly. Detailed clinical re-examination, cardiac and skeletal imaging did not reveal any abnormalities in P1 or P2 other than mild hip dysplasia. Conclusion: This report broadens the phenotypic spectrum of growth disorders associated with FBN1 mutations. Identical mutations give rise to a wide phenotypic spectrum, ranging from isolated short stature to a more classic picture of GD2 with cardiac involvement, distinct facial dysmorphisms and various skeletal anomalies. (C) 2016 S. Karger AG, Basel
Palavras-chave
Fibrillin 1, Acromelic dysplasia, Geleophysic dysplasia, Acromicric dysplasia, Short stature
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