BRWD3 and Pes cavus: Intriguingly, in humans mutations of the CUL4B, which encode a ubiquitin 3 ligase subunit cause an X-linked syndrome characterized by intellectual impairment, macrocephaly, central obesity, hypogonadism, pes cavus and tremor [17], a phenotype that largely overlaps with that observed in patients carrying BRWD3 mutations/deletions, including the present case.