LAUSR

The semaphorins constitute a large family of secreted and membrane‐associated proteins that regulate many developmental processes, including neural circuit assembly, bone formation and angiogenesis. Recently, bi‐allelic loss‐of‐function variants in SEMA3A (semaphorin 3A) were identified in a single patient with a particular pattern of multiple congenital anomalies (MCA). Using homozygosity mapping combined with exome sequencing, we identified a homozygous SEMA3A variant causing a premature stop codon in an 8 year old boy with the same pattern of MCA. The phenotype of these patients is characterized by postnatal short stature, skeletal anomalies of the thorax, a minor congenital heart or vascular defect, camptodactyly, micropenis, and variable additional anomalies. Motor development is delayed in both patients, and intellectual development is delayed in one patient. Our observation of a second case supports the notion that bi‐allelic mutations in SEMA3A cause an autosomal recessive type of syndromic short stature.