Septo-optic dysplasia

Septo-optic dysplasia
Classification and external resources
Specialty	medical genetics
ICD-10	Q04.4
ICD-9-CM	742.2
OMIM	182230
DiseasesDB	32732
MeSH	D025962

Septo-optic dysplasia (SOD), (de Morsier syndrome)^[1]^[2] is a rare congenital malformation syndrome featuring underdevelopment of the optic nerve, pituitary gland dysfunction, and absence of the septum pellucidum (a midline part of the brain). Two of these features need to be present for a clinical diagnosis — only 30% of patients have all three.^[3]

Neuroradiologically, intracranial malformations associated with septo-optic dysplasia include agenesis of the septum pellucidum, schizencephaly, and lobar holoprosencephaly.

Presentation

Optic nerve

The optic nerve hypoplasia is generally manifested by nystagmus (involuntary eye movements, often side-to-side) and a smaller-than-usual optic disc. The degree of visual impairment is variable, and ranges from normal vision to complete blindness. When nystagmus develops, it typically appears by 1–8 months of age, and usually indicates that there will be a significant degree of visual impairment, but the severity is difficult to predict in infancy. Although there are many measures to compensate for visual impairment, there are few treatments available to induce normal optic nerve function.^[4]

Pituitary

The degree of pituitary deficiency is also variable, and ranges from normal function, to deficiency of both anterior and posterior hormones. It is often unclear if the hypopituitarism is due to a primary pituitary dysfunction or is secondary to a hypothalamic dysfunction. Hypopituitarism in this syndrome is most often manifested by growth hormone deficiency. If severe, it can lead to diagnosis in the first days of life by causing hypoglycemia, jaundice, and micropenis (if a boy). The cause of the jaundice is unknown, and an unusual aspect of it (compared to most neonatal jaundice) is that it can be largely a conjugated (direct) hyperbilirubinemia suggestive of obstructive liver disease. It typically resolves over several weeks once hormone replacement is begun. All of the pituitary hormones can be replaced, and this is the treatment for deficiencies. Septo-optic dysplasia is one of the most common forms of congenital growth hormone deficiency.

Septum pellucidum

The brain effects are also variable. Seizures sometimes occur. Prediction of intellectual outcome in infancy is difficult. Various types of early intervention or equivalent programs can help a child reach full developmental potential.

Variability

Septo-optic dysplasia is a highly variable disorder. It is rare for siblings to present with identical features of the septo-optic dysplasia spectrum. Many patients present with additional developmental defects outside the septo-optic dysplasia triad. In particular digital defects are common.

Causes

Septo-optic dysplasia is a developmental disorder resulting from a defect of normal embryological development. There is no single cause of septo-optic dysplasia. Septo-optic dysplasia has been linked to young maternal age.^[5]

Genetic

Rare familial recurrence has been reported, suggesting at least one genetic form (HESX1).^[6] In addition to HESX1, mutations in OTX2, SOX2 and PAX6 have been implicated in de Morsier syndrome,^[7] but in most cases SOD is a sporadic birth defect of unknown cause and does not recur with subsequent pregnancies.

Valproate toxicity

Further information: Sodium valproate

Valproate toxicity in utero has been implicated as a possible etiology of septo-optic dysplasia.^[8]

References

↑ synd/2548 at Who Named It?
↑ G. de Morsier. Études sur les dysraphies, crânioencéphaliques. III. Agénésie du septum palludicum avec malformation du tractus optique. La dysplasie septo-optique. Schweizer Archiv für Neurologie und Psychiatrie, Zurich, 1956, 77: 267-292.
↑ Gleason, CA; Devascar, S (5 October 2011). "Congenital malformations of the Central Nervous System". Avery's Diseases of the Newborn (9 ed.). Saunders. p. 857. ISBN 1437701345.
↑ http://www.msnbc.msn.com/id/21134540/vp=40678268&#40678268&from=en-us_msnhp&snid=18424776
↑ McNay DE, Turton JP, Kelberman D, et al. (2006). "HESX1 mutations are an uncommon cause of septo-optic dysplasia and hypopituitarism". J Clin Endocrinol Metab. 92 (2): 691–7. doi:10.1210/jc.2006-1609. PMID 17148560.
↑ Dattani MT, Martinez-Barbera JP, Thomas PQ, et al. (1998). "Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse". Nat. Genet. 19 (2): 125–33. doi:10.1038/477. PMID 9620767.
↑ "OMIM". Genetics Home Reference - Septo-Optic Dysplasia. Retrieved 5 February 2015.
↑ Jerome F. Strauss and Robert L. Barbieri (eds), "Yen and Jaffe's reproductive endocrinology; physiology, pathophysiology, and clinical management", 6th ed, 2009, p. 421.

Congenital malformations and deformations of nervous system (Q00–Q07, 740–742)

Brain

Neural tube defect	Anencephaly Acephaly Acrania Acalvaria Iniencephaly Encephalocele Arnold–Chiari malformation

Other	Microcephaly Congenital hydrocephalus Dandy–Walker syndrome other reduction deformities Holoprosencephaly Lissencephaly Pachygyria Hydranencephaly Septo-optic dysplasia Megalencephaly CNS cyst Porencephaly Schizencephaly Polymicrogyria Bilateral frontoparietal polymicrogyria

Spinal cord

Neural tube defect	Spina bifida Rachischisis

Other	Currarino syndrome Diastomatomyelia Syringomyelia

Genetic disorder, protein biosynthesis: Transcription factor/coregulator deficiencies

(1) Basic domains

1.2	Feingold syndrome Saethre–Chotzen syndrome

1.3	Tietz syndrome

(2) Zinc finger
DNA-binding domains

2.1	(Intracellular receptor): Thyroid hormone resistance Androgen insensitivity syndrome PAIS MAIS CAIS Kennedy's disease PHA1AD pseudohypoaldosteronism Estrogen insensitivity syndrome X-linked adrenal hypoplasia congenita MODY 1 Familial partial lipodystrophy 3 SF1 XY gonadal dysgenesis

2.2	Barakat syndrome Tricho–rhino–phalangeal syndrome

2.3	Greig cephalopolysyndactyly syndrome/Pallister–Hall syndrome Denys–Drash syndrome Duane-radial ray syndrome MODY 7 MRX 89 Townes–Brocks syndrome Acrocallosal syndrome Myotonic dystrophy 2

2.5	Autoimmune polyendocrine syndrome type 1

(3) Helix-turn-helix domains

3.1	ARX Ohtahara syndrome Lissencephaly X2 MNX1 Currarino syndrome HOXD13 SPD1 Synpolydactyly PDX1 MODY 4 LMX1B Nail–patella syndrome MSX1 Tooth and nail syndrome OFC5 PITX2 Axenfeld syndrome 1 POU4F3 DFNA15 POU3F4 DFNX2 ZEB1 Posterior polymorphous corneal dystrophy Fuchs' dystrophy 3 ZEB2 Mowat–Wilson syndrome

3.2	PAX2 Papillorenal syndrome PAX3 Waardenburg syndrome 1&3 PAX4 MODY 9 PAX6 Gillespie syndrome Coloboma of optic nerve PAX8 Congenital hypothyroidism 2 PAX9 STHAG3

3.3	FOXC1 Axenfeld syndrome 3 Iridogoniodysgenesis, dominant type FOXC2 Lymphedema–distichiasis syndrome FOXE1 Bamforth–Lazarus syndrome FOXE3 Anterior segment mesenchymal dysgenesis FOXF1 ACD/MPV FOXI1 Enlarged vestibular aqueduct FOXL2 Premature ovarian failure 3 FOXP3 IPEX

3.5	IRF6 Van der Woude syndrome Popliteal pterygium syndrome

(4) β-Scaffold factors
with minor groove contacts

4.2	Hyperimmunoglobulin E syndrome

4.3	Holt–Oram syndrome Li–Fraumeni syndrome Ulnar–mammary syndrome

4.7	Campomelic dysplasia MODY 3 MODY 5 SF1 SRY XY gonadal dysgenesis Premature ovarian failure 7 SOX10 Waardenburg syndrome 4c Yemenite deaf-blind hypopigmentation syndrome

4.11	Cleidocranial dysostosis

(0) Other transcription factors

0.6	Kabuki syndrome

Ungrouped

Transcription coregulators

Coactivator:	CREBBP Rubinstein–Taybi syndrome

Corepressor:	HR (Atrichia with papular lesions)

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