A female phenotype with coffin-lowry syndrome

Coffin-Lowry syndrome (CLS, MIM # 303600) is a rare X-linked semi-dominant mental retardation disorder (XLMR). It was first reported independently by Coffin et al. [1] and Lowry et al. [2] and recognized as a novel syndrome of neurocognitive impairment, growth retardation, facial dysmorphism, puffy proximal digits, tapering digits and progressive skeletal changes by Temtamy et al. [3] in 1975. It has an estimated incidence of 1:50,000 to 1:1,000,000 live births. Approximately 70–80% of patients are sporadic cases [4]. It is caused by mutations in a serine threonine kinase RSK2 (RPS6KA3) gene located in region Xp22.2–p22 [5]. The RSK2 gene is expressed in various brain structures, including the cortex, cerebellum, and hippocampus [6]. RSK2 mutations have been detected in approximately 50% of CLS patients and to date, more than 140 RSK2 mutations have been identified (Coffin-Lowry mutation database: http://wwwulpmed.ustrasbg.fr/chimbio/diag/coffin). About 80% of the mutations arise de novo, most of them are private, found in only one family [7,8].