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1999-05-24-23 Septo-optic dysplasia  © Jeanty www.thefetus.net/


Septo-optic dysplasia

Updated 2006-01-18 by Juliana Leite, MD

Original text 1999-05-24 Philippe Jeanty, MD, PhD & Sandra R Silva, MD

Synonym: Morsier syndrome

Definition: Septo-optic dysplasia (SOD) is a syndrome characterized by anomalies of cerebral mid line structures, such as absence of the septum pellucidum, congenital optic nerve dysplasia and panhypopituitarism, leading to multiple endocrine defects (diabetes insipidus, hypogonadotropic hypogonadism, hypothyroidism, adrenal insufficiency, abnormal thyrotropin releasing hormone test, gonadotropin releasing hormone test, and GH releasing hormone). SOD may represent a mild form of holoprosencephaly.

Incidence: Unknown but rare.

Etiolopathology: Although a vascular disruption sequence has been postulated, more recent genetic anomalies seem to explain the findings (see genetic anomalies below). A possible mendelian inheritance (autosomal-recessive) has also been postulated. Also illicit drugs use may play a causative role in brain development anomalies. In addition, intrauterine exposure to valproic acid has been associated with an increased risk of central nervous system abnormalities, primarily neural tube defects.

Clinical findings


• Central nervous system: seizures, mental retardation, atrophy of the optic nerve, dilatation of suprasellar cistern, empty sella, cortical atrophy and dystrophic corpus callosum, anterior cephalocele have also been described.
• Face: hypotelorism, microphthalmia, visual impairment with nystagmus, unilateral or bilateral optic disk hypoplasia with double rim appearance (choroidal pigment in the outer margin and pale nerve tissue in the inner), variable visual loss, coloboma, strabismus, astigmatisms, bilateral cleft lip and palate, high arched palate and flat nasal bridge.
• Endocrine system: low growth rate and short stature. The most common problem is growth hormone deficiency (93%), followed by ACTH deficiency (57%), hypothyroidism (53%), and diabetes and gonadotrophin deficiency. Hypothalamic disfunction is the basic origin of these endocrine abnormalities. Septo-optic dysplasia is responsible for approximately 4% of all growth hormone deficiencies in children.

Diagnosis: Absence of the septum pellucidum is probably the most typical finding. Sometimes, the standard sonographic views of the brain, obtained along the axial planes, at mid-gestation, can fail to identify this absence. It can be explained for the close proximity of the walls of the lateral ventricles, normal in size that could generate an artifact resembling a normal cavum septum pellucidum. The magnetic resonance demonstration of hypoplastic optic tracts can get the diagnosis, for sure. Hypotelorism, enlarged cerebral ventricles, communicating lateral ventricles, and bilateral cleft lip and palate have also been recognized prenatally.

Genetic anomalies: Mutations of the homeo box gene HESX1 is suggested as the etiological cause at least in a subset of patients. An Arg53Cys missense mutation was found in two children within the HESX1 homeodomain, which destroyed its ability to bind target DNA. Mice that are deficient of the HESX1 homeobox gene present with neural defects similar to that of SOD.

Differential diagnosis: Several variants with associated schizencephaly, dysgenesis of the corpus callosum, or microphthalmos, as well as incomplete forms, have been described. Lobar holoprosencephaly may also resemble SOD.

Recurrence risk: Unknown.

Prognosis: The variable degree of mental deficit (from minimal to severe) as well as the presence of multiple endocrine dysfunctions will affect the prognosis for each infant. Prevention of hyperthermia (in case of fever), dehydration (fever and diabetes insipidus), and other endocrine dysfunction should be searched and corrected.

Management: Termination of pregnancy can be offered before viability. Standard prenatal care is not altered when continuation of the pregnancy is chosen. Confirmation of diagnosis after birth is important for genetic counseling. Prevention of recurrent hypoglycemic episodes, seizures, and hormonal imbalances may improve the overall prognosis.


 
References

1. Pilu G, Tani G, Carletti A, Malaigia S, Ghi T, Rizzo N. Difficult early sonographic diagnosis of absence of the fetal septum pellucidum. Ultrasound Obstet Gynecol 2005;25(1):70-2
2. Orrico A, Galli L, Zappella M et al. Septo-optic dysplasia with digital anomalies associated with maternal multidrug abuse during pregnancy. Eur J Neurol 2002;9(6):679-82
3. McMahon CL, Braddock SR. Septo-optic dysplasia as a manifestation of valproic acid embryopathy. Teratology 2001;64(2):83-6

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