Test Directory

Sotos syndrome 1 (SOTOS1; MIM 117550), Sotos syndrome 2 (SOTOS2; MIM 614753), Weaver syndrome (WVS; MIM 277590), and Simpson-Golabi-Behmel syndrome, type 1 (SGBS1; MIM 312870) are overgrowth syndromes characterized by pre- and postnatal overgrowth, accelerated osseous maturation, characteristic craniofacial appearance, and developmental delay. Sotos and Weaver syndromes are autosomal dominant disorders, which show considerable phenotypic overlap; however, these disorders also have some distinct clinical features.  Congenital heart anomalies, scoliosis, renal abnormalities and seizures are common in Sotos syndrome, while WVS is associated with campodactyly, umbilical hernia, hoarse cry in infancy, and soft, doughy skin. Over 90% of individuals with Sotos syndrome have a mutation affecting the NSD1 gene (SOTOS1), which encodes a histone methyltransferase involved in gene regulation. WVS is caused by mutations in the EZH2 gene, which also encodes a histone methyltransferase. A few individuals with a Sotos-like syndrome have been reported to have mutations in NFIX (SOTOS2), which encodes a transcription factor involved in gene regulation.  NFIX mutations can also cause Marshall-Smith syndrome (MRSHSS; MIM 602535), but this syndrome is not an overgrowth disorder. MRSHSS is an autosomal dominant disorder characterized by short stature, accelerated skeletal maturation, developmental delay, failure to thrive, respiratory difficulties, prominent forehead, proptosis, micrognathia, and kyphoscoliosis.  Simpson-Golabi-Behmel syndrome is an X-linked recessive overgrowth disorder. SBGS1 can be distinguished from other overgrowth disorders by its unique set of features, including coarse facies, macrostomia, macroglossia, cleft palate, postaxial polydactyly, rib abnormalities, umbilical hernia, and congenital heart defects. SBGS1 is caused by mutations in the GPC3 gene, which encodes glypican 3, a heparin sulfate proteoglycan involved in several cell signaling pathways. Simpson-Golabi-Behmel syndrome, type 2 (SGBS2; MIM 300209) clinically overlaps with SGBS1. SGBS2 is more severe and often lethal in infancy.  It is caused by mutations in the OFD1 gene. Mutations in this gene can also cause Orofaciodigital syndrome I (OFD1; MIM 311200) and Joubert syndrome 10 (JBTS10; MIM 300804). Mutations in the PIGA gene have also been reported in some patients with a SGBS2 phenotype (Simpson-Golabi-Behmel syndrome, PIGA related).