OMIM ID:
Heart and Brain Malformation Syndrome
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Microphthalmia is the cardinal ocular malformation. Hypertelorism has been described. Poor vision without further description has also been reported.
Systemic Features
The ears are low-set, malformed, and posteriorly rotated. The forehead is prominent and there is usually a wide anterior fontanel. The nasal bridge is wide and frequently depressed while the lower lip is full and may be everted and split. The palate is highly arched. Physical growth is slow. A ventricular septal defect is often present while the valves are hypoplastic and the aortic arch can be interrupted.
Microcephaly is often present and there may a profound delay in psychomotor development with truncal hypotonia and hyperreflexia in the limbs. Brain imaging shows generalized atrophy with decreased myelination. Cerebellar vermis hypoplasia has been reported. Two of 5 patients were reported to have Dandy-Walker malformations, and a thin corpus callosum. Seizures may occur.
Genetics
Inheritance
Homozygous mutations in the SMG9 gene (19q13.31) are responsible for this condition so far reported in 5 individuals in two unrelated consanguineous Arab families.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.