Nashville, TN

Definition: Syndrome characterized by anomalies of the cerebral midline structures[1] caused by an insult probably occurring at 6-week gestation[2]. The main anomalies are absence of the septum pellucidum, congenital optic nerve dysplasia, and hypothalamic panhypopituitarism, which leads to multiple endocrine defects such as diabetes insipidus, hypogonadotrophic hypogonadism, hypothyroidism, and minimal growth hormone serum levels1^,2. Most authors agree that this syndrome may be within the spectrum of holoprosencephaly.

Case report:

This 26-weeks fetus was referred for "abnormal images of the brain". We demonstrated the following images. The rest of the anatomy of this fetus was unremarkable as was the anamnestic information. There is also a 1.6 MB videoclip that demonstrates the anomaly better. The striking finding was all the material in the ventricles and we suspected either some choroid plexus tumor (but why bilateral ?) or a blood clot. The videoclip demonstrates the findings better but also that I got blind-sided by the "bleed" and forgot to observe 2 crucial findings:

1. the absence of the corpus callosum (also visible indirectly from the wide interhemispheric fissure on the images below) and
2. the absence of the cavum septum pellucidum.... duh !!!!!!! incredible how one can easily miss the "absence" of something !

A repeat examination 2 weeks later provided the following images. There was essentially no changes to the intraventricular material but the walls of the ventricles appeared more echogenic and we considered this consistent with a evolving intraventricular bleed. Note (particularly in the 6th image below) the appearance of "lace-like" or strand material in the ventricles.

The last exam performed 4 weeks after the first demonstrated the organization of the clot and the same findings of absence of the corpus callosum and of the cavum septum pellucidum.

1. intraventricular bleed

2. absence of the corpus callosum  and

3. the absence of the cavum septum pellucidum

A C-section was performed at 36+1 week’s gestational age due to pregnancy-induced hypertension. A 2800gr.girl baby was born without surgical complications.

After birth, the baby had difficulty to start breathing and several episodes of persistent apnea required CPR. Tachypnea, retractions and nasal flaring with persistent respiratory distress required a 24 hr period intubation for respiratory insufficiency.

The physical exam of the newborn on her 2nd day of life demonstrated a normal phenotype, including the face. An ophthalmological exam revealed bilateral retinal ischemia. Problems sucking and swallowing were the main problem for the first days. The baby was discharged from the NICU in the 9th day.

We lost track of the baby but the parents were very kind in coming to us later to provide us some follow-up. They have actually even created a web site about their daughter: http://www.faithyancy.com/ .

The sonographic brain findings during the second and fifth day of life were:

• Agenesis of the corpus callosum
• Bilateral ventricular dilatation with multiple “septations” involving the periventricular white matter
• Normal posterior fossa and 4th ventricle
• No fluid around the cerebral convexities
• Reduced sulci and giri for the expected weeks of gestation

The MRI findings at 7 months of age included:

• Absence of the corpus callosum and cavum septum pellucidum
• Enlarged 3rd and lateral ventricles above the tentorium (cerebral atrophy)
• Normal size fourth ventricle
• Marked degree of supratentorial atrophy
• Bilateral small subacute subdural hematomas (left-10mm, right-6mm)

The baby was finally diagnosed as having Septo Optic Dysplasia. Actually she is 21 months old, is severely developmentally delayed and she does have a variety of challenges and handicaps. She has blindness, nystagmus, seizures, hormonal problems, learning disabilities and mental retardation, and developmental delay especially in her head growth.

Synonyms: Morsier syndrome1^,2^,[3]. 

Incidence: Unknown but very rare. ^1,2 

Etiology^:   During the past years two theories have been postulated. One theory postulates the probability of an inherited dominant, recessive or multifactorial trait. In 1985, Blethen and Weldon described two first cousins with panhypopituitarism, one of whom had septo-optic dysplasia[4]. A vascular disruption sequence has also been hypothesized during the last six years1^,[5].

Genetic anomalies: An Arg53Cys missense mutation was found in two children within the HESX1 homeodomain, which destroyed its ability to bind target DNA. Mice deficient of HESX1 homeobox gene present with neural defects similar to those of septo-optic dysplasia1^,[6].

Pathogenesis: This abnormal developmental process consists of a defect in the cerebral midline structures, specially the septum pellucidum, the anterior hypothalamus, the posterior hypophysis, optic nerve and chiasms2.

Sex ratio: M1:F1.2

Recurrence risk: unknown.2

Gene mapping and linkage: unknown.2

Prenatal ultrasound diagnosis: The most typical finding is absent cavum septum pellucidum.1^,2^,[7].  Other sonographic findings related to holoprosencephaly can also be seen: hypotelorism, enlarged communicating cerebral ventricles, bilateral clefts (lip and palate) and microophthalmia. In every patient with absent cavum septum pellucidum a septo-optic dysplasia must be excluded.1^,2

Clinical findings:

·        Central nervous system: the affected child can have hypoglycemic seizures and variable degrees of mental retardation. Atrophy of the optic nerve, dilatation of suprasellar cistern, empty sella, cortical atrophy and dystrophic corpus callosum, can be seen on CT and MRI scans1^,2^,[8]. Anterior cephalocele has also been described.[9]

·        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.^1,2,[10]   

·        Endocrine system: abnormalities become apparent in early childhood particularly with low growth rate and short stature. The multiplicity and severity of endocrine abnormalities is greatly variable. 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.2 Septo-optic dysplasia is responsible for approximately 4% of all growth hormone deficiencies in children.[11]

Differential diagnosis: abnormalities that can potentially affect the midline cerebral structures should always be excluded: schizencephaly, holoprosencephaly, agenesis of the corpus callosum, hydrocephalus, anterior encephalocele, porencephaly, hydranencephaly, and median cleft facial syndrome.1^,2^,[12]

Prognosis: It will be determined specially by the degree of mental retardation and endocrine disfunction.1^,2

Management: Termination of the pregnancy is a parental decision. However diagnosis must be very accurate. Prenatal care is not altered when continuation of the pregnancy is the choice. Prevention of recurrent hypoglycemic episodes, seizures, and hormonal imbalances may improve the overall prognosis.1^,2

References

[1] Fleisher AC, Manning FA, Jeanty P, Romero R, Sonography in Obstetrics and Gynecology. S.  6^th edition. The Mc graw Hill Compinies, Inc. 2001

[2] Buyse ML: Birth Defect Encyclpedia. Cambridge, England, Blackwell Scientific, 1990

[3] Williams JL, Faerber EN. Septooptic dysplasia (de Morsier syndrome). J Ultrasound Med. 1985 May;4(5):265-6.

[4] Blethen SL, Weldon VV. Hypopituitarism and septooptic "dysplasia" in first cousins. Am J Med Genet. 1985 May;21(1):123-9.

[5] Brodsky, MC. Hypothesis: septo-optic dysplasia is a vascular disruption sequence. Suv Opthalmol

[6] Traboulsi EI. Ocular malformations and developmental genes.J  AAPOS. 1998 Dec;2(6):317-23.Review.

[7] Barkovich AJ, Norman D. Absence of the septum pellucidum: a useful sign in the diagnosis of congenital brain malformations. AJR Am J Roentgenol. 1989 Feb;152(2):353-60.

[8] Curnes JT, Laster DW, Koubek TD, Moody DM, Ball MR, Witcofski RL. MRI of corpus callosal syndromes. AJNR Am J Neuroradiol. 1986 Jul-Aug;7(4):617-22.

[9] Yokota A, Matsukado Y, Fuwa I, Moroki K, Nagahiro S. Anterior basal encephalocele of the neonatal and infantile period. Neurosurgery. 1986 Sep;19(3):468-78.

[10] Zeki SM. Optic nerve hypoplasia and astigmatism: a new association. Br J Ophthalmol. 1990 May;74(5):297-9.

[11] August GP, Lippe BM, Blethen SL, Rosenfeld RG, Seelig SA, Johanson AJ, Compton PG, Frane JW, McClellan BH, Sherman BM. Growth hormone treatment in the United States: demographic and diagnostic features of 2331 children. J Pediatr. 1990 Jun;116(6):899-903.

[12] Barkovich AJ, Norman D. Absence of the septum pellucidum: a useful sign in the diagnosis of congenital brain malformations. AJR Am J Roentgenol. 1989 Feb;152(2):353-60.