Clinical Characteristics
Ocular Features
Most patients have congenital cataracts which may be mild and "oil drop" in appearance. The eyes appear far apart, the eyebrows are broad, and the palpebral fissures may slant upward or downward. Ptosis has been reported. Aphakic glaucoma has been reported in one juvenile who had unilateral cataract surgery at 5 months of age.
Systemic Features
The phenotype is heterogeneous and not all patients have all features. The facial features are said to resemble those of the Down syndrome with brachycephaly, a high forehead, and a flat midface with shallow orbits and malar hypoplasia. The ears are small, low-set, and posteriorly rotated. The nose is short and the nasal bridge is broad and flat. The mouth is small and the upper lip is thin. The scalp hair may be sparse and the nails sometimes appear dystrophic.
The fingers are sometimes brachydactylous and tapered. Short stature is common and the joints may have limited motion. Dislocation of the radial heads is seen rarely while radioulnar synostosis has been seen in a few individuals. Postnatal short stature is common.
Seizures often occur. The ventricles appear large and cerebral atrophy has been reported. Intellectual disability and mental retardation are common. However, at least one individual attended university although he had been diagnosed in childhood with Asberger disease. Neurosensory hearing loss is common.
Genetics
Inheritance
This autosomal dominant condition results from heterozygous mutations in the MAF (16q32.2) gene. At least one mother/son transmission event has been reported.
Many of the same features are seen in what has been called the Fine-Lubinsky syndrome (601353) but without mutations in the MAF gene. It may not be a unique disorder.
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission