OMIM ID:
Microphthalmia, Syndromic 6
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Ultrasound evaluation reveals globe size to vary widely from extremely small (6 mm) to normal axial length. Clinical anophthalmia is often diagnosed. Both anophthalmia and microphthalmia may exist in the same individual. True anophthalmia has been confirmed in some patients in which no ocular tissue was detectable with ultrasound examination. In such cases the optic nerves and chiasm are often missing as well. Iris colobomas are common and these may extend posteriorly. Myopia is sometimes present.
The ERG reveals generalized rod and cone dysfunction in some eyes, but may be normal in others. In many eyes the ERG is nonrecordable. Cataracts are frequently present.
Systemic Features
Digital and hand anomalies are common. The hands are often described as broad and the thumbs may be low-placed. The nails can appear dysplastic and postaxial polydactyly is often present. Mild webbing of the fingers has been reported as well. Microcephaly and the cranium can be misshapen. A high arched palate is often present and clefting has also been noted. Micrognathia may be present. Some evidence of physical growth retardation is often evident.
Pituitary hypoplasia is not uncommon and may be associated with hypothyroidism and cryptorchidism with hypospadias, and a small or bifid scrotum.
The brain anomalies vary considerably. Many patients have mild to moderate developmental delays with some learning difficulties. Sensorineural hearing loss is often present. Hypoplasia of the vermis, thinning of the corpus callosum, widening of the lateral ventricles, and occasional generalized cortical atrophy, at least in older individuals, have been described.
Genetics
Inheritance
This is an autosomal dominant condition caused by a point mutation in BMP4 (bone morphogenetic protein-4) (14q22-q23). A number of chromosomal deletions involving this gene have also been identified in individuals who have this syndrome but since contiguous genes such as OTX2 and SIX6 may also be involved, the phenotype is more likely to be associated with other anomalies including genital hypoplasia, pituitary hypoplasia, absence of the optic nerves and/or chiasm, developmental delay, digital malformations, and cerebellar dysplasia.
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