Case Report: A Novel FGD1 c.16G>A Variant Associated With Atypical Aarskog-Scott Syndrome in a Chinese Toddler

<title>Abstract</title> <p>Background Aarskog-Scott syndrome (AAS) is an X-linked developmental disorder caused by variants in FGD1. Most affected males are recognized through craniofacial, skeletal, genital, and growth findings, but mild or incomplete presentations can delay etiologic diagnosis. Case presentation We report a Chinese boy aged 2 years and 3 months who presented with persistent speech delay, mild growth retardation, an 8-month delay in bone age, and a neonatal atrial septal defect that closed spontaneously. He had no typical facial, skeletal, or genital malformations of classic AAS. Baseline Gesell developmental assessment at 27.4 months showed disproportionate neurodevelopmental impairment, with a language developmental quotient of 64.9 and a language developmental age of 17.8 months. Trio whole-exome sequencing and Sanger validation identified a maternally inherited hemizygous FGD1 c.16G &gt; A (p.Ala6Thr; NM_004463.3) variant in exon 1. The variant was absent from gnomAD, 1000 Genomes, ClinVar, and HGMD in the source report, but in silico tools did not support a damaging effect; it was therefore classified as a variant of uncertain significance under ACMG/AMP criteria. At follow-up on June 3, 2026, after individualized speech-language, social, cognitive, and dietary intervention, the language developmental quotient increased to 72.2 and the language developmental age increased to 21.0 months. Conclusions This case adds clinical evidence for rare N-terminal FGD1 variants and supports considering atypical AAS in boys with unexplained language delay and mild growth impairment after common endocrine, nutritional, and environmental causes have been excluded.</p>