OMIM ID:
Septooptic Dysplasia
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Optic nerve hypoplasia is most characteristic ocular feature of this syndrome. It may be bilateral but often is unilateral. The hypoplastic nerve head can have a ‘double margin’. The outer ring consists of the junction of the sclera with the lamina cribrosa while the inner margin is darker and represents the junction of the RPE with the abnormally small nerve containing less than the normal number of axons. Visual acuity depends upon the degree of nerve hypoplasia. Nystagmus and strabismus may be present.
Systemic Features
Midline brain defects are common. This usually consists of an absent septum pellucidum but sometimes absence or thinning of the corpus callosum as well. An ‘empty sella’ with a dysplastic pituitary gland and deficiencies in hormone output can be present. Hypoglycemia, hypogonadism, short stature and corticotrophin deficiency may result. There is considerable clinical heterogeneity and few patients have all of these features. Only 29% of patients have the full spectrum of brain, optic nerve, and pituitary abnormalities. It has been proposed that the severity of the brain midline defects can be correlated with the degree of endocrinopathy. Mental retardation and features of autism spectrum disorders may be present.
A few patients have been reported with skeletal deformities such as syndactyly and hypoplastic digits. Rare males have underdeveloped genitalia.
Genetics
Inheritance
The majority of cases occur sporadically. Among rare cases with a family history, homozygosity of a mutation in the HESX1 gene (3p21.2-p21.1) has been found suggesting an autosomal recessive etiology. It seems likely that there remains considerable genetic heterogeneity and it is doubtful that septooptic dysplasia is a unique disorder.
Bilateral optic nerve hypoplasia (165550) also occurs without the CNS malformations but it results from a different mutation.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.