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Rigshospitalet - a part of Copenhagen University Hospital
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Novel truncating variants in FGD1 detected in two Danish families with Aarskog-Scott syndrome and myopathic features

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Aarskog-Scott syndrome (AAS) is a developmental disorder, caused by disease-causing hemizygous variants in the FGD1 gene. AAS is characterized by dysmorphic features, genital malformation, skeletal anomalies, and in some cases, intellectual disability and behavioral difficulties. Myopathy has only been reported once in two affected siblings diagnosed with AAS. Only few adult cases have been reported. This article reports four adults with AAS (three male cases and one female carrier) from two unrelated Danish families, all males presented with variable features suggestive of myopathy. All four carried novel hemizygous pathogenic variants in the FGD1 gene; one family presented with the c.2266dup, p.Cys756Leufs*19 variant while the c.527dup; p.Leu177Thrfs*40 variant was detected in the second family. All males had some mild myopathic symptoms or histological abnormalities. Case 1 had the most severe myopathic phenotype with prominent proximal muscular fatigue and exercise intolerance. In addition, he had multiple deletions of mtDNA and low respiratory chain activity. His younger nephew, case 3, had difficulties doing sports in his youth and had a mildly abnormal muscle biopsy and relatively decreased mitochondrial enzyme activity. The singular case from family 2 (case 4), had a mildly myopathic muscle biopsy, but no overt myopathic symptoms. Our findings suggest that myopathic involvement should be considered in AAS.

Original languageEnglish
JournalAmerican Journal of Medical Genetics. Part A
Volume188
Issue number7
Pages (from-to)2251-2257
Number of pages7
ISSN1552-4825
DOIs
Publication statusPublished - Jul 2022

Bibliographical note

© 2022 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.

    Research areas

  • Adult, Denmark, Dwarfism, Face/abnormalities, Female, Genetic Diseases, X-Linked, Genitalia, Male/abnormalities, Guanine Nucleotide Exchange Factors/genetics, Hand Deformities, Congenital/diagnosis, Heart Defects, Congenital, Humans, Male, Syndrome

ID: 79164078