Attention-deficit/hyperactivity disorder (ADHD) and variable clinical expression of Aarskog-Scott syndrome due to a novel FGD1 gene mutation (R408Q)

Mutations of the FGD1 gene are responsible for a significant proportion of patients with Aarskog-Scott syndrome (AAS), an X-linked disorder characterized by short stature, brachydactyly, urogenital abnormalities, and a typical dysmorphic facial appearance. Although mental retardation does not occur significantly in AAS, this condition has been described associated with various degrees of mental impairment and/or behavioral disorders in some patients. In particular, attention deficit hyperactivity disorder (ADHD) is reported as a common characteristic of AAS. However, AAS/ADHD reported patients have been only clinically described, and diagnosis never has been confirmed on molecular basis. We present here a unique case of a 16-years-old patient presenting with ADHD, lower intelligence quotient, and dysmorphic features. Although the clinical features were not completely typical of AAS, genetic analysis demonstrated a novel FGD1 missense mutation (R408Q). The case we report confirms the highly variable expressivity of AAS and first documents that the FGD1 gene may play a role in ADHD susceptibility. We suggest that FGD1 analysis may be adequate in ADHD patients who exhibit dysmorphic features suggestive of AAS, also in the absence of the full phenotypical spectrum.