de Morsier syndrome

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.

Pedigree: 
Autosomal recessive
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
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