Holoprosencephaly and Recurrent Episodes of Severe Neurogenic Hypernatremia

Holoprosencephaly (HPE) is a severe and complex malformation caused by incomplete cleavage of the prosencephalon and incomplete development of paramedian structures. Many causes have been recognized as responsible for this malformation including maternal diabetes, chromosomal abnormalities, and heterozygous mutations, involving four major genes (SHH, Z1C2, SIX3, and TGIF) and other less frequently reported genes. HPE has frequently been reported as a feature of complex malformative syndromes such as Smith–Lemli–Opitz syndrome, CHARGE syndrome (acronym of Coloboma, Heart defects, choanal Atresia, Retardation of growth and/or development, Genitourinary malformation and Ear abnormalities), and Rubinstein–Taybi syndrome. Moreover, children with HPE may present with other anomalies aside from those of the brain and face, including endocrine disorders such as diabetes insipidus, adrenal hypoplasia, hypogonadism, thyroid hypoplasia, and growth hormone deficiency. We report a boy with typical clinical signs of HPE including neuroradiologic findings resembling severe congenital hydrocephalus. The patient also presented with a specific metabolic anomaly consisting of recurrent episodes of hypernatremia.