Heart and Brain Malformation Syndrome

Background and History: 

This is a rare hereditary syndrome with malformations in the heart and brain.

Clinical Correlations: 

Clinically useful signs are present at birth, consisting of small heads and sometimes small eyes.  The ears are low-set, malformed, and posteriorly rotated.  There is poor muscle control (hypotonia) of the trunk while the limb reflexes are hyperactive.  The nasal bridge is depressed and wide giving the appearance of abnormally widely spaced eyes.  The palate in the mouth is highly arched while the lower lip is full and sometimes split (cleft lip).  The heart, its valves, and the aorta may also have developmental defects.

Physical growth and psychomotor development are slow.  Brain imaging shows severe abnormal development of tissues in the skull.  Seizures may occur.  Vision is poor but the cause of this remains unknown.


A change (mutation) in both members of a specific pair of genes is responsible for this severe and complex condition inherited in an autosomal recessive pattern.  Parents who carry a single mutation are clinically normal but when both carry the mutation each of their children have a 25% risk of inheriting the two mutations and manifesting this disorder.

Diagnosis and Prognosis: 

The facial and skull features should suggest this condition at birth but it is rare and not widely known.  Pediatricians, cardiologists, ophthalmologists, and neurologists may collaborate in the diagnosis and care of this disorder.  The physical defects are sufficiently severe so that death may occur within a few years of life.  No treatment is known.

Additional Information
Autosomal recessive