I. Introduction
Holoprosencephaly (HPE) is a relatively rare developmental defect in the median structures of the brain and face that results from impaired cleavage of the embryonic forebrain. HPE occurs in 5–12/10,000 live births (1), whereas an estimated 40 per 10 000 cases are seen among human abortions indicating a high rate of fetal loss (2).
Patients with holoprosencephaly frequently display craniofacial anomalies including midline facial clefts, cyclopia and nasal anomalies. , They may also suffer from dysfunctions in the pituitary glands presenting with diabetes insipidus (3).
Holoprosencephaly is etiologically diverse and can be perturbed by both genetic and environmental causes, either individually or more likely in combination with other congenital disorders. Approximately 65% of holoprosencephaly appears to be sporadic and cannot be ascribed to any known cause. Clinically, there is a nearly continuous spectrum of malformations consistent with HPE which can manifest with variable expressivity and/or penetrance, demonstrated by the segregation analysis of familial cases (4).
Patients manifest a wide spectrum of clinical conditions and neurologic dysfunction. Severity of symptoms correlates with the degree of hemispheric nonseparation (5). Because the clinical spectrum of this defect has been inadequately described in milder forms, we aim to report an Iranian patient with holoprosencephaly with associated DI, which was found to be refractory to conventional treatments.