Holoprosencephaly with Hypoplasia of the Optic Nerves, Dwarfism, and Agenesis of the Septum Pellucidum

Optic nerve axons: life and death before birth

“…197 Hoyt et al 198 were the first to clearly demonstrate hypopituitarism in patients with septo-optic dysplasia and since then a variety of hormonal defects have been described, ranging from isolated growth hormone, adrenocorticotrophic, or antidiuretic hormone deficiency to panhypopituitarism. [199][200][201][202][203][204][205] Evaluation of these endocrine disturbances is now the province of the paediatric endocrine specialist. Hypothyroidism may be the most common significant abnormality, 206,207 but there is such variation in incidence in the various studies and Figure 21 Aetiological and associated features of ONH.…”

“…In holoprosencephaly, a variable midline facial defect is associated with a single cerebral ventricle, and absence of the corpus callosum and septum pellucidum; there is also a wide variety of other brain defects causing similar problems. 189,202,212,213 Pathological studies in holoprosencephaly have shown absence of the olfactory apparatus, which forms a link with Kallmann's syndrome 214 in which gonadotrophin, growth hormone, and antidiuretic hormone deficiency and anosmia are associated with forebrain abnormalities (Figure 25). …”

Craniotelencephalic dysplasia in sisters: Further delineation of a possible syndrome

“…Furthermore, aberrations of early brain morphogenesis result in unusual dural reflections that can give rise to alterations in the nature and position of cranial sutures [Moss, 1959[Moss, , 1975Muke, 1972;Smith and Tondury, 19781. It was documented that one of the sisters had optic nerve hypoplasia and an absent septum pellucidum, a combination first demonstrated by de Morsier in 1956 and referred to as septo-optic dysplasia. This malformation frequently occurs together with other major CNS anomalies, most consistently absence of the pituitary gland [Hoyt et al, 19701; less common associated anomalies are absence of the olfactory tracts, agenesis of the corpus callosum, porencephalic cysts, lissencephaly, and holoprosencephaly [Rakic and Yakovlev, 1968;Ellenberger and Runyan, 1970;Hale and Rice, 1974;Pate1 et al, 1975;Zaias and Becker, 1978;Landrieu and Evrard, 19791. Thus, their presence together in patient 1 is not surprising as they comprise a single developmental field defect.…”

Pituitary function in a patient with septo-optic dysplasia and pituitary dwarfism (Kaplan-Grumbach-Hoyt syndrome)

“…It is believed that the developmental disorder of the septum pellucidum and the anomaly of the optic nerve are caused by the same teratogenic agents (Ellenberg and Runyan, 1970;Brook et al, 1972). The joint appearance of GH insufficiency and diabetes insipidus in some patients indicates that hypopituitarism is of secondary, hypothalamic origin leading to deficient pituitary stimulation (Kaplan et al, 1970;Billson and Hopkins, 1972;Patel et al, 1975;Toublanc et al, 1976).…”

“…Since the publication of this description septo-optic dysplasia and pituitary dwarfism is considered a syndrome including pituitary dwarfism, hypoplasia of the optic nerve and malformation of the prosencephalon. Further cases were described by Ellenberg and Runyan (1970), Brook et al (1972), Harris and Haas (1972), Billson and Hopkins (1972), Patel et al (1975) and Toublanc et al (1976).…”