A rare case of Coffin–Lowry syndrome accompanied by a copper-beaten skull appearance

Abstract

Coffin-Lowry syndrome (CLS), usually a result of loss-of-function mutations in the RPS6KA3 gene located at Xp22.2, is a very rare genetic condition. It is associated with different phenotypes, including dysmorphic facial features, neuro-developmental impairment, short stature, and skeletal deformities. Here we describe a four-year-old boy who had distinct clinical features of CLS: moderate mental and motor retardation, brachycephaly, microcephaly, hypertelorism, low-set and prominent ears, down- slanted palpebral fissures, a depressed nasal bridge with thick nasal alae and septum, a high-arched palate, widely spaced teeth, and retrognathia. Genetic analysis revealed a pathogenic variant in the RPS6KA3 gene, NM_004586.3: exon 22: c.2186G>A: (p.Arg729Gln). His healthy mother was a heterozygous carrier of the variant. In addition to the clinical findings, the patient’s X-ray revealed a very rare feature of a copper-beaten skull appearance. The link between CLS and a copper-beaten skull has never been reported before. This case demonstrates the variability in presentation of CLS and signifies the association of a rare radiographic finding of copper-beaten skull with CLS. Based on this case, we recommend screening skull radiographs at the clinic for copper-beaten skulls in patients with CLS.