Neurodevelopmental Disorder with Progressive Microcephaly, Spasticity, and Brain Anomalies

Background and History: 

This is a rare inherited disorder of brain development with severe, progressive neurological deficiencies.

Clinical Correlations: 

Infants appear 'floppy' at birth and spontaneous movements are limited.  This results in poor feeding activity and difficulty breathing.  There is little developmental progression.  Severe cognitive delays result in profound mental retardation in most cases.  Seizures are common.

Physical signs include low-set and posteriorly rotated ears, a short nose, a highly arched palate, a short lower jaw, excess hair, stiff large joints and highly flexible small joints, a deformity of the breastbone, and sometimes extra digits.  The skull appears abnormally small and falls behind as the body grows.

MRI brain imaging reveals a large variety of deficits some which are progressive.  These can result in an early demise, in infancy or early childhood, usually from respiratory difficulties. 

Genetics: 

This is an autosomal recessive disorder resulting from mutations in both members of a specific pair of genes.  Parents who carry one copy are clinically normal but when both carry a single copy of the mutation they confer a 25% risk of this condition to each of their offspring.

Diagnosis and Prognosis: 

The clinical features described here could lead to the suspected diagnosis at birth or during the neonatal period.  Special attention should be directed to maintaining respiratory function.  This likely requires teamwork among ophthalmologists, pediatricians, neurologists, and orthopedists.  Brain imagining and gene studies are necessary to confirm the diagnosis.

No treatment has been reported and the prognosis is poor.

Additional Information
Inheritance/Pedigree: 
Autosomal recessive