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Septo-optic dysplasia

Reviewed March 2010

What is septo-optic dysplasia?

Septo-optic dysplasia is a disorder of early brain development. Although its signs and symptoms vary, this condition is traditionally defined by three characteristic features: underdevelopment (hypoplasia) of the optic nerve, abnormal formation of structures along the midline of the brain, and pituitary hypoplasia.

The first major feature, optic nerve hypoplasia, is the underdevelopment of the optic nerves, which carry visual information from the eyes to the brain. In affected individuals, the optic nerves are abnormally small and make fewer connections than usual between the eyes and the brain. As a result, people with optic nerve hypoplasia have impaired vision in one or both eyes. Optic nerve hypoplasia can also be associated with unusual side-to-side eye movements (nystagmus) and other eye abnormalities.

The second characteristic feature of septo-optic dysplasia is the abnormal development of structures separating the right and left halves of the brain. These structures include the corpus callosum, which is a band of tissue that connects the two halves of the brain, and the septum pellucidum, which separates the fluid-filled spaces called ventricles in the brain. In the early stages of brain development, these structures may form abnormally or fail to develop at all. Depending on which structures are affected, abnormal brain development can lead to intellectual disability and other neurological problems.

The third major feature of this disorder is pituitary hypoplasia. The pituitary is a gland at the base of the brain that produces several hormones. These hormones help control growth, reproduction, and other critical body functions. Underdevelopment of the pituitary can lead to a shortage (deficiency) of many essential hormones. Most commonly, pituitary hypoplasia causes growth hormone deficiency, which results in slow growth and unusually short stature. Severe cases cause panhypopituitarism, a condition in which the pituitary produces no hormones. Panhypopituitarism is associated with slow growth, low blood sugar (hypoglycemia), genital abnormalities, and problems with sexual development.

The signs and symptoms of septo-optic dysplasia can vary significantly. Some researchers suggest that septo-optic dysplasia should actually be considered a group of related conditions rather than a single disorder. About one-third of people diagnosed with septo-optic dysplasia have all three major features; most affected individuals have two of the major features. In rare cases, septo-optic dysplasia is associated with additional signs and symptoms, including recurrent seizures (epilepsy), delayed development, and abnormal movements.

How common is septo-optic dysplasia?

Septo-optic dysplasia has a reported incidence of 1 in 10,000 newborns.

What genes are related to septo-optic dysplasia?

In most cases of septo-optic dysplasia, the cause of the disorder is unknown. Researchers suspect that a combination of genetic and environmental factors may play a role in causing this disorder. Proposed environmental risk factors include viral infections, specific medications, and a disruption in blood flow to certain areas of the brain during critical periods of development.

At least three genes have been associated with septo-optic dysplasia, although mutations in these genes appear to be rare causes of this disorder. The three genes, HESX1, OTX2, and SOX2, all play important roles in embryonic development. In particular, they are essential for the formation of the eyes, the pituitary gland, and structures at the front of the brain (the forebrain) such as the optic nerves. Mutations in any of these genes disrupt the early development of these structures, which leads to the major features of septo-optic dysplasia.

Researchers are looking for additional genetic changes that contribute to septo-optic dysplasia.

Related Gene(s)

Changes in these genes are associated with septo-optic dysplasia.

  • HESX1
  • OTX2
  • SOX2

How do people inherit septo-optic dysplasia?

Septo-optic dysplasia is usually sporadic, which means that the condition typically occurs in people with no history of the disorder in their family.

Less commonly, septo-optic dysplasia has been found to run in families. Most familial cases appear to have an autosomal recessive pattern of inheritance, which means that both copies of an associated gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. In a few affected families, the disorder has had an autosomal dominant pattern of inheritance, which means one copy of an altered gene in each cell is sufficient to cause the condition.

Where can I find information about diagnosis or management of septo-optic dysplasia?

These resources address the diagnosis or management of septo-optic dysplasia and may include treatment providers.

  • Genetic Testing Registry: Septo-optic dysplasia sequence (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0338503)
  • MedlinePlus Encyclopedia: Growth Hormone Deficiency (http://www.nlm.nih.gov/medlineplus/ency/article/001176.htm)
  • MedlinePlus Encyclopedia: Hypopituitarism (http://www.nlm.nih.gov/medlineplus/ency/article/000343.htm)

You might also find information on the diagnosis or management of septo-optic dysplasia in Educational resources (http://www.ghr.nlm.nih.gov/condition/septo-optic-dysplasia/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/septo-optic-dysplasia/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about septo-optic dysplasia?

You may find the following resources about septo-optic dysplasia helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for septo-optic dysplasia?

  • De Morsier syndrome
  • septooptic dysplasia
  • SOD

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about septo-optic dysplasia?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding septo-optic dysplasia?

autosomal ; autosomal dominant ; autosomal recessive ; cell ; corpus callosum ; deficiency ; disability ; dysplasia ; embryonic ; epilepsy ; familial ; gene ; growth hormone ; hormone ; hypoglycemia ; hypogonadism ; hypoplasia ; incidence ; inheritance ; neurological ; nystagmus ; optic nerve ; pattern of inheritance ; pituitary gland ; recessive ; reproduction ; risk factors ; septum ; short stature ; SOD ; sporadic ; stature ; syndrome ; tissue

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Dattani MT, Martinez-Barbera JP, Thomas PQ, Brickman JM, Gupta R, Mårtensson IL, Toresson H, Fox M, Wales JK, Hindmarsh PC, Krauss S, Beddington RS, Robinson IC. Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse. Nat Genet. 1998 Jun;19(2):125-33. (http://www.ncbi.nlm.nih.gov/pubmed/9620767?dopt=Abstract)
  • Dattani MT, Robinson IC. HESX1 and Septo-Optic Dysplasia. Rev Endocr Metab Disord. 2002 Dec;3(4):289-300. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12424431?dopt=Abstract)
  • Kelberman D, Dattani MT. Genetics of septo-optic dysplasia. Pituitary. 2007;10(4):393-407. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17587179?dopt=Abstract)
  • Kelberman D, Dattani MT. Septo-optic dysplasia - novel insights into the aetiology. Horm Res. 2008;69(5):257-65. doi: 10.1159/000114856. Epub 2008 Feb 6. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18259104?dopt=Abstract)
  • 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. Epub 2006 Dec 5. (http://www.ncbi.nlm.nih.gov/pubmed/17148560?dopt=Abstract)
  • Miller SP, Shevell MI, Patenaude Y, Poulin C, O'Gorman AM. Septo-optic dysplasia plus: a spectrum of malformations of cortical development. Neurology. 2000 Apr 25;54(8):1701-3. (http://www.ncbi.nlm.nih.gov/pubmed/10762523?dopt=Abstract)
  • Patel L, McNally RJ, Harrison E, Lloyd IC, Clayton PE. Geographical distribution of optic nerve hypoplasia and septo-optic dysplasia in Northwest England. J Pediatr. 2006 Jan;148(1):85-8. (http://www.ncbi.nlm.nih.gov/pubmed/16423603?dopt=Abstract)
  • Tajima T, Hattorri T, Nakajima T, Okuhara K, Sato K, Abe S, Nakae J, Fujieda K. Sporadic heterozygous frameshift mutation of HESX1 causing pituitary and optic nerve hypoplasia and combined pituitary hormone deficiency in a Japanese patient. J Clin Endocrinol Metab. 2003 Jan;88(1):45-50. (http://www.ncbi.nlm.nih.gov/pubmed/12519827?dopt=Abstract)
  • Thomas PQ, Dattani MT, Brickman JM, McNay D, Warne G, Zacharin M, Cameron F, Hurst J, Woods K, Dunger D, Stanhope R, Forrest S, Robinson IC, Beddington RS. Heterozygous HESX1 mutations associated with isolated congenital pituitary hypoplasia and septo-optic dysplasia. Hum Mol Genet. 2001 Jan 1;10(1):39-45. (http://www.ncbi.nlm.nih.gov/pubmed/11136712?dopt=Abstract)
  • Webb EA, Dattani MT. Septo-optic dysplasia. Eur J Hum Genet. 2010 Apr;18(4):393-7. doi: 10.1038/ejhg.2009.125. Epub 2009 Jul 22. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19623216?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: March 2010
Published: November 24, 2014