Septooptic Dysplasia

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

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.

Treatment
Treatment Options: 

All patients with optic nerve hypoplasia should be evaluated for midline brain anomalies and endocrinopathy.  There is no treatment for the optic nerve hypoplasia but low vision aids could be helpful in selected cases with bilateral nerve dysplasia.  The hormonal deficiencies, of course, need to be corrected with appropriate replacements. 

References
Article Title: 

Endocrine status in patients with optic nerve hypoplasia: relationship to midline central nervous system abnormalities and appearance of the hypothalamic-pituitary axis on magnetic resonance imaging

Birkebaek NH, Patel L, Wright NB, Grigg JR, Sinha S, Hall CM, Price DA, Lloyd IC, Clayton PE. Endocrine status in patients with optic nerve hypoplasia: relationship to midline central nervous system abnormalities and appearance of the hypothalamic-pituitary axis on magnetic resonance imaging. J Clin Endocrinol Metab. 2003 Nov;88(11):5281-6.

PubMed ID: 
14602752

References

Garcia-Filion P, Borchert M. Optic Nerve Hypoplasia Syndrome: A Review of the Epidemiology and Clinical Associations. Curr Treat Options Neurol. 2012 Dec 13. [Epub ahead of print].

PubMedID: 23233151

McNay DE, Turton JP, Kelberman D, Woods KS, Brauner R, Papadimitriou A, Keller E, Keller A, Haufs N, Krude H, Shalet SM, Dattani MT. HESX1 mutations are an uncommon cause of septooptic dysplasia and hypopituitarism. J Clin Endocrinol Metab. 2007 Feb;92(2):691-7.

PubMedID: 17148560

Birkebaek NH, Patel L, Wright NB, Grigg JR, Sinha S, Hall CM, Price DA, Lloyd IC, Clayton PE. Endocrine status in patients with optic nerve hypoplasia: relationship to midline central nervous system abnormalities and appearance of the hypothalamic-pituitary axis on magnetic resonance imaging. J Clin Endocrinol Metab. 2003 Nov;88(11):5281-6.

PubMedID: 14602752

Carvalho LR, Woods KS, Mendonca BB, Marcal N, Zamparini AL, Stifani S, Brickman JM, Arnhold IJ, Dattani MT. A homozygous mutation in HESX1 is associated with evolving hypopituitarism due to impaired repressor-corepressor interaction. J Clin Invest. 2003 Oct;112(8):1192-201.

PubMedID: 14561704