Many inherited disorders cause malformations in multiple systems such as this one that affect skeletal, facial, neurological, ocular, and other structures. The clinical features vary widely with few patients having all of the signs.
The most obvious sign at birth may be the presence of extra fingers and toes in some infants. There may be a cleft lip and palate and the lower jaw is sometimes underdeveloped. The eyes can appear widely separated and have difficulty tracking smoothly. Some individuals have crossing of the eyes (strabismus) and jerky movements (nystagmus). The ears are often low-set and rotated toward the back of the head. Sometimes the tongue appears forked and there may be nodules present. There may be adhesion between the cheeks and the gums. Congenital heart disease is common and many individuals have periods of rapid breathing. Poor temperature control has been reported with episodic high temperatures. Both physical and mental development may be delayed. Parts of the brain (the cerebellum) may also be underdeveloped. Some patients are mentally retarded and short stature is common.
Only a few families have been reported and the transmission patterns suggest autosomal recessive disease. Gene studies have identified at least two mutations among families. The best estimate of recurrence risk seems to be about 25% among families in which both parents carry one of these mutations.
Many of the clinical signs have been found in certain other syndromes as well and the classification of these disorders is not clear.
Pediatricians are most likely to suspect this condition at birth but the diagnosis in many cases requires a multidisciplinary approach with neurologists, ophthalmologists, oral surgeons, orthopedists and medical geneticists. The full clinical picture is probably unknown based on the rarity of this condition. Nothing is known about the prognosis. Most individuals require lifelong monitoring with intervention as needed for breathing difficulties, heart problems, cleft lip and palate, and cosmesis. Physical therapy, breathing assistance, educational support, low vision aids and nutritional support may all be of benefit.