017\u2005When the (genetics) penny drops…

Abstract

Background Drop attacks are commonly referred to Neurologists and their differential diagnosis is wide. The family history and clinical examination proved critical in establishing the (very rare) cause here. Clinical case A 21-year-old man was seen with drop attacks provoked by auditory stimuli. He had global developmental delay, and dysmorphic features- traits shared by his mother, sister and brother (none of whom had neurological complaints or severe learning disability [LD]). Examination revealed hypertelorism, low slanting palpebral fissures, ‘fleshy’ hands & tapering fingers and kyphoscoliosis. His mother and sister had similar hands. An archived genetic test confirmed the presence of a mutation in RPS6KA3, supporting the diagnosis of Coffin-Lowry syndrome (CLS). CLS is rare (1:50,000) and X-linked dominant. In addition to LD and dysmorphic features (as here), stimulus-induced drop attacks (responsive to Clonazepam, usually) are common. CLS affects women less severely, due to the ameliorating effect of the non-mutated allele in females. The mildly affected brother of the proband has Klinefelter’s syndrome. Our patient’s attacks were completely abolished with Clonazepam. Key points The differential diagnosis of drop attacks is wide. Don’t forget the family! Genetic testing, as well as elucidating diagnoses, can point to effective therapies.