This is a recently described syndrome of complex physical and mental changes that includes short stature and intellectual disability. It is somewhat unusual as infants usually appear normal at birth but their facial appearances can change remarkably in the first several decades.
Head size may appear somewhat small at birth but often seems normal. Birth weight and length are normal but many infants seem limp or ‘floppy’. About half of individuals have constipation early in the first year of life which sometimes requires emergency surgery due to defects in bowel motility. General skeletal and head growth soon seems to fall behind and many patients are short in stature. Intellectual disability is present to some degree and many are called mentally retarded. Epilepsy, congenital heart defects, and genitourinary anomalies are common. The teeth may be crooked and crowded.
The eyes sometimes appear too far apart and are often ‘crossed’. Some young patients have cataracts. The eyebrows are often sparse and appear ‘wedge-shaped’ with the thickest portion near the nose. The lid openings slant downwards. The colored portion of the eye may be incomplete and the pupil can resemble a keyhole instead of being round. The earlobes appear flattened and often have a central depression.
Among the remarkable aspects of this disorder are the progressive changes in facial morphology over the second and third decades of life. The eyes appear more deeply set, the nasal bridge tends to flatten, and the lower jaw elongates. The tip of the nose lengths somewhat and appears to override the upper lip to some extent.
Many patients have a happy disposition and smile freely. However, significant numbers have emotional and behavioral problems. IQ cannot be tested.
This is an autosomal dominant disorder resulting from the mutation (change) in a single copy of a gene. Individuals with the mutation do not reproduce so that the gene change in a patient usually is the result of a new mutation. This means that the risk to sibs is small, and, for the same reasons, normal sibs do not transmit the mutation to their children.
The diagnosis is most likely made by a pediatrician or neurologist in consultation with a medical geneticist. Many individuals live to adulthood but little is known about longevity. There is no treatment for the syndrome but individual problems such as cataracts and constipation can be corrected or treated. Additional treatment is supportive and symptomatic. Early speech and physical therapy can be helpful.