Warburg micro syndrome (WARBM) is a rare autosomal recessive disorder characterized by postnatal severe intellectual disability, microcephaly, ocular findings such as congenital cataract, microcornea, microphthalmia and optic atrophy, and hypogonadism. RAB3GAP1 mutations are mostly causative. This child was presented because of having two patients from the same family. First son of the family had WARBM and he died.
A 12-month-old boy was admitted to our clinic because of congenital cataracts, micropenis, and cryptorchidism. Parents were second cousins. Birth weight was 2800 g. At 2 months of age, he underwent bilaterally phacoemulsification. His weight was 6.8 kg (<3p), length 75.5 cm (25-50p), and head circumference was 41 cm (<3p). He had low-set and large ears, a prominent nasal root, ptosis, high-arched palate, and micrognathia. Ophthalmological examination revealed hypotelorism, microphthalmia, and microcornea. He had truncal hypotonia, increased muscle tone in both legs, poor head control, and was unable to sit without support. He had bilateral cryptorchidism, a micropenis (stretched penile length of 20 mm), and scrotal hypoplasia. USG revealed both testicles within the inguinal canals. Karyotype was 46, XY, inv(9)(p12q13). Failed to get visual message as a result of Flash VEP. Cranial MRI showed atrophy of the corpus callosum and cerebral cortex. Sequence analyses of the RAB3GAP1 gene revealed that he was homozygous for the splice donor mutation c.748+1G>A. His deceased brother possessed the same mutation. Both parents were heterozygous for the mutation.
WARBM is rarely presented in siblings. The importance of pre-conception genetic counseling in the family who has children with same disorders is highlighted.