Biallelic SEMA3A defects cause a novel type of syndromic short stature.

Chromosomal microarray testing is commonly used to identify disease causing de novo copy number variants in patients with developmental delay and multiple congenital anomalies. In such a patient we now observed an 150 kb deletion on chromosome 7q21.11 affecting the first exon of the axon guidance molecule gene SEMA3A (sema domain, immunoglobulin domain (Ig), short basic domain, secreted, (semaphorin) 3A).

7 Mb de novo deletion within 8q21 in a patient with distal arthrogryposis type 2B (DA2B).

We report on a 7 11/12 years old male patient with normal mental development, club feet, ulnar deviation and mild camptodactyly as well as facial dysmorphism including high forehead, small mouth, broad nasal bridge, epicanthus, high palate, brachycephalus, short neck, and dysplastic ears consistent with distal arthrogryposis type 2B (DA2B). Mutational analysis of the genes MYH3, TNNI2, TNNT3 and TPM2, known to cause DA2B revealed no apparent disease causing mutation. Molecular karyotyping using a 250 K SNP array revealed a heterozygous de novo 7 Mb deletion of 8q21.

A de novo 7.6Mb tandem duplication of 14q32.2-qter associated with primordial short stature with neurosecretory growth hormone dysfunction, distinct facial anomalies and mild developmental delay.

We delineate a pure "distal 14q duplication" phenotype, characterized by primordial short stature, mild developmental delay, and distinct facial dysmorphism with high forehead, mild hypertelorism, broad nasal bridge, dysplastic ear helices, short philtrum, thin and "cupid bow" upper lip, broad mouth, and micrognathia.