This is a hereditary disorder of marked developmental delay resulting from maldevelopment of the brain. It is one of multiple conditions in which a change in DNA (mutation) results in skeletal and neurological defects.
Skull and facial deformities are evident at birth. The skull may be somewhat small and misshapen and the ears are placed low and rotated toward the back. The neck often appears short while the forehead is prominent and the face appears triangular. The upper lip is thin and the mouth is usually open. The eyelids appear to droop (ptosis) and the opening slants downward. The eyes are often not aligned (strabismus) and have jerky movements (nystagmus).
Infants appear floppy and have poor muscle tone (hypotonia). They have difficulty feeding and are often constipated with the result that they fail to thrive. Gastric tube placement may be necessary to ensure proper nutrition.
Most patients do not develop speech and do not develop the ability to move independently. Seizures are often present. Brain imaging in some patients shows abnormal brain development although some individuals do not show this. Abnormal spinal curvature (scoliosis), hip contractures, wasting of muscle tissue, and purposeless movements have been described in some infants.
This autosomal recessive disorder results from mutations in a specific gene. Both copies of the gene must be changed (mutated). Parents who carry only one copy are clinically normal but the offspring of two such parents each have a 25% risk of inheriting both mutated copies.
Pediatricians, geneticists, and neurologists are likely to collaborate in the diagnosis of this condition. The diagnosis may be suspected at birth but the complete clinical features may not be evident until early childhood when it is evident that the child is not achieving normal milestones (speech, sitting, walking, etc.). Brain imaging and an EEG (electroencephalogram) can provide further clues.
No treatment for the general condition has been reported but placement of a gastric feeding tube can be helpful. Nothing is known regarding longevity.