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Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.
Synonyms: de Morsier's syndrome, pituitary hormone deficiency combined HESX1-related
- Optic nerve hypoplasia.
- Midline brain abnormalities (including absence of the corpus callosum and septum pellucidum).
- Hypothalamic-pituitary endocrine deficiencies.
Associated features include developmental delay, seizures, visual impairment, sleep disturbance, precocious puberty, obesity, anosmia, sensorineural hearing loss and cardiac anomalies.
The SOD phenotype is highly heterogeneous and diagnosis is made in the presence of at least two of these three features. Only about a third of patients have all three features but patients with any component of the syndrome should be screened for the other features too. The cause of SOD is unknown but viral infections, gestational diabetes, environmental teratogens, vascular or degenerative injury and genetic mutations have all been considered as possible predisposing factors. Management can be complicated and can entail lifelong multidisciplinary input.
This is a rare condition, in the order of 1 per 100,000 of the population. A study from Greater Manchester and Lancashire has identified cases being more common where high unemployment, low income and teenage pregnancies exist. The association with young mothers has been previously reported in Glasgow.However, there is still a debate as to whether maternal age is significant.
Genetics of SOD
Most cases are sporadic but several familial cases have been described with an increasing number of mutations in developmental transcription factors implicated, including HESX1, SOX2, SOX3 and OTX2.
Although it appears to be genetic in origin, it rarely runs in families.This suggests that mutation is more often spontaneous than inherited.
- Suspicions can be raised at mid-trimester ultrasound scanning and the condition can be diagnosed but it can also easily be missed.
- The child may appear normal at birth or there may be problems such as poor development of male genitalia.
- Unexplained hypoglycaemia may suggest pituitary inadequacy.
- Vision testing and screening in young children may reveal the first sign of abnormality.
- Susceptibility to infection may suggest a problem and it merits investigation.
- Seizures (particularly in patients with developmental delay) and/or sleep disturbances can occur.
There is a broad spectrum of pituitary problems ranging from isolated growth hormone deficiency to panhypopituitarism.
- There are hypoplastic optic discs with a classical double margin.
- There may be severe sight impairment in one or both eyes; 80% of these patients are considered legally severely sight impaired.
- Nystagmus and astigmatism are other common features.
- The septum pellucidum ± corpus callosum are absent in about half of patients.
- Other midline abnormalities may affect the fornix, the septum pellucidum, the corpus callosum, and cerebellum.
- Developmental delay can occur.
- A majority of patients have some psychomotor impairment.
- Associations with autism have been described.
- The most consistent clinical feature is short stature associated with poor or absent growth hormone. Weight and head circumference are normal for size.
- Lack of growth hormone and other pituitary hormones can make individuals susceptible to neonatal hypoglycaemia. There may also be hypernatraemia.
- Other pituitary hormones are often deficient and there may be diabetes insipidus, although the posterior pituitary or neurohypophysis has a different embryological origin from the anterior pituitary of adenohypophysis.
- Hormonal imbalance can lead to a precocious puberty.
- NB: if there is illness, the lack of adrenocorticotrophic hormone (ACTH) can precipitate an adrenal crisis and sudden death.
- Thermoregulation may be deficient.
Classification according to MRI findings
A series of 55 patients was divided into four groups based on septum pellucidum and hypothalamic-pituitary axis appearance on MRI scan:
- In group 1 both were normal.
- In group 2 there was abnormal septum pellucidum and normal hypothalamic-pituitary axis.
- In group 3 there was normal septum pellucidum and abnormal hypothalamic-pituitary axis.
- In group 4 both were abnormal.
None of the patients in group 1 had endocrine dysfunction compared with 22% in group 2, 35% in group 3 and 56% in group 4. Group 2 was the most common to experience precocious puberty.
- Brain imaging with MRI is an important investigation and an MRI to measure the size of the optic nerves can confirm the diagnosis. MRI will indicate the degree of structural abnormality and this indicates the likely endocrine abnormality.
- Tests of pituitary function may show hypopituitarism.
- Developmental assessment is likely to show delayed development.
A lifelong multidisciplinary approach is required to optimise growth and development and to lead as normal life as possible.
- Growth hormone may be administered.
- If ACTH is deficient, the correct dose of cortisone to permit health and growth is a delicate balance.
- Management of puberty requires judgement. It may involve induction of puberty or delaying it if premature.
- Psychomotor retardation complicated by poor vision requires specialist help.
- A lifelong multidisciplinary approach is important to optimise growth and development.
Early detection and treatment reduces disease-related morbidity, and can be life-saving.
Further reading and references
Septo-optic Dysplasia; Online Mendelian Inheritance in Man (OMIM)
Septo-Optic Dysplasia; National Institute of Neurological Disorders and Stroke
Kelberman D, Dattani MT; Septo-optic dysplasia - novel insights into the aetiology. Horm Res. 200869(5):257-65. doi: 10.1159/000114856. Epub 2008 Feb 6.
Fard MA, Wu-Chen WY, Man BL, et al; Septo-optic dysplasia. Pediatr Endocrinol Rev. 2010 Sep8(1):18-24.
Kaur S, Jain S, Sodhi HB, et al; Optic nerve hypoplasia. Oman J Ophthalmol. 2013 May6(2):77-82. doi: 10.4103/0974-620X.116622.
Webb EA, Dattani MT; Septo-optic dysplasia. Eur J Hum Genet. 2010 Apr18(4):393-7. doi: 10.1038/ejhg.2009.125. Epub 2009 Jul 22.
de Ferran K, Paiva IA, Gilban DL, et al; Septo-optic dysplasia. Arq Neuropsiquiatr. 2010 Jun68(3):400-5.
Patel L, McNally RJ, Harrison E et al.; Geographical distribution of optic nerve hypoplasia and septo-optic dysplasia in Northwest England. J Pediatr. 2006 Jan148(1):85-8. [abstract]
Murray PG, Paterson WF, Donaldson MD.; Maternal age in patients with septo-optic dysplasia. J Pediatr Endocrinol Metab. 2005 May18(5):471-6. [abstract]
McCabe MJ, Alatzoglou KS, Dattani MT; Septo-optic dysplasia and other midline defects: the role of transcription factors: HESX1 and beyond. Best Pract Res Clin Endocrinol Metab. 2011 Feb25(1):115-24. doi: 10.1016/j.beem.2010.06.008.
Lepinard C, Coutant R, Boussion F, et al; Prenatal diagnosis of absence of the septum pellucidum associated with septo-optic dysplasia. Ultrasound Obstet Gynecol. 2005 Jan25(1):73-5.
Birkebaek NH, Patel L, Wright NB, et al; 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 Nov88(11):5281-6.
Birkebaek NH, Patel L, Wright NB, et al; Optic nerve size evaluated by magnetic resonance imaging in children with optic nerve hypoplasia, multiple pituitary hormone deficiency, isolated growth hormone deficiency, and idiopathic short stature. J Pediatr. 2004 Oct145(4):536-41.
Al-Senawi R, Al-Jabri B, Al-Zuhaibi S, et al; Septo-optic dysplasia complex: Clinical and radiological manifestations in Omani children. Oman J Ophthalmol. 2013 Sep6(3):193-8. doi: 10.4103/0974-620X.122277.