Holoprosencephaly (HPE) is a brain malformation resulting from a primary defect in development of the basal forebrain during early gestation. Prenatal genetic and environmental factors and birth outcomes were described in a population of 104 children with holoprosencephaly referred to three clinical centers from 1998 through 2002. The mean child age was 4 years. Of cases karyotyped, 9% presented with a chromosomal abnormality. This study of living children with holoprosencephaly, the majority of whom are cytogenetically normal, provides new information on the subsample of children with a less severe phenotype. Most children were born at term; about 51% were microcephalic at birth. Consistent with previous research, the association between HPE and maternal history of diabetes merits further investigation. Several findings have important implications for future research. Only 22% of the children in this study sample were diagnosed with holoprosencephaly prenatally. The vast majority of children (72%) were diagnosed with HPE between birth and 1 year of age. Also, 19% of the cases referred to the Carter Centers with HPE were not confirmed on scan review. When possible, future population-based epidemiological studies should emphasize mechanisms that identify children with HPE outside of the newborn period and confirm the diagnosis by review of MRI or high quality CT brain scan.
Objective. To investigate the incidence of endocrinopathies in holoprosencephaly (ΗΡΕ) and correlate the severity of the endocrinopathies with the neuroanatomic abnormalities. Study design. We reviewed the histories and medical records of 117 children with ΗΡΕ for endocrinopathies and related treatments. Neuroimaging studies were graded for severity of ΗΡΕ, hypothalamus non-separation, and pituitary abnormalities.
Results. Diabetes insipidus (DI) occurred in 70%of patients with classic ΗΡΕ. The severity of the DI correlated with the grade of ΗΡΕ and hypothalamic non-separation (p <0.0001). Anterior pituitary dysfunctions were much less common. Hypothyroidism was identified in 11% of patients, hypocorticism in 7%, and growth hormone deficiency in 5%. Only one patient with middle interhemispheric variant of holoprosencephaly (MIH) had any of these disorders. Conclusions. Patients with ΗΡΕ have a high incidence of DI that may be related to the failure of cleavage of hypothalamic nuclei. Anterior pituitary dysfunctions are much less common than DI.
These findings support our clinical impression of improvement on important target behaviors such as aggression, disruptiveness, self-injury, stereotypy, and social withdrawal. Low-dose risperidone appears to be well tolerated in children with DS+ASD, although concerns about weight gain and metabolic alterations may limit its usefulness over the long term in some children.
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