Background: Holoprosencephaly (HPE) is a brain malformation that results from a defect in the patterning of the forebrain. Children with the most severe forms of HPE have endocrine deficits, in addition to neurologic and visual impairment. Forebrain abnormalities and pituitary hormone deficiencies are also part of the clinical spectrum of septo-optic dysplasia (SOD).
Aim: Describe the spectrum of endocrinopathies in children with HPE and compare their characteristics to those with severe SOD, as defined by the combination of optic nerve hypoplasia, pituitary hormone deficiencies and defects in the midline structures.
Results: Twenty-two patients with severe HPE presented to our department; we compared their characteristics to those of 28 children with severe SOD. Children with HPE presented at a mean age of 1.4±1.3 years, with a mean height SDS of −2.08±1.0. Diabetes insipidus (DI) was observed in 54.6%, either in isolation (18.2%) or in combination with anterior pituitary hormone deficiencies (36.4%). More than half (54.5%) were diagnosed as growth hormone deficient, 40.9% had ACTH deficiency and 18.2% had TSH deficiency. The majority of patients with HPE had an absent (56.3%) or dysplastic (25%) corpus callosum, and more than half had an absent septum pellucidum (56.3%). There was no significant difference in the appearance of the midline structures between the two groups. The incidence of DI was significantly higher in children with HPE compared to those with SOD (54.5 vs 18.5%, P<0.05), whilst TSH deficiency was more frequent in patients with SOD (48.1 vs 18.2%, P<0.05). There was no significant difference in the incidence of GHD (54.5 vs 59.3%, P>0.05) and ACTH deficiency (40.9 vs 59.3%, P>0.05) in children with HPE and SOD respectively.
Conclusions: Children with severe HPE and SOD present with a variable but distinct spectrum of pituitary hormone deficiencies. The greater involvement of hypothalamic nuclei in children with HPE may account for the increased incidence of DI.
10 - 12 Nov 2009
British Society for Paediatric Endocrinology and Diabetes