Coffin‐Lowry Syndrome

Abstract

Coffin‐Lowry syndrome is a distinctive X‐linked dominantly inherited condition that has a birth prevalence of about 1/50,000 and is caused by mutations in the RDS6KA3 gene. The hemizygous male presents with significant mental retardation and a facial appearance characterized by a prominent forehead and supraorbital ridges; down‐slanting palpebrae and hypertelorism; a distinctive nose with a low bridge, thick septum, small and anteverted nares; and full and patulous lips with the lower lip everted. The hands are soft and hyperextensible with tapering fingers, and there are a number of minor and nonspecific radiographic changes that may aid in the diagnosis. Progressive kyphoscoliosis can be an important complication. Clinical expression in the heterozygous female can range from completely normal intelligence and appearance, through mild degrees of intellectual impairment and facial dysmorphia, to expression equaling that in the male. There is evidence to suggest a significant risk of premature death, primarily related to pulmonary and cardiac complications but in some cases remaining unexplained.