Hydrocephalus, Autosomal Dominant

Clinical Features

Braddock et al. (1993) reported 4 cases of sagittal craniosynostosis and the Dandy-Walker malformation (posterior fossa cyst, hypoplasia of the cerebellar vermis and often hydrocephalus) and suggested that they represented an autosomal dominant multiple malformation syndrome distinct from other disorders in which either craniosynostosis or the Dandy-Walker malformation is present. A mother and her 2 sons were affected. The 2 sons had developmental delay, and the mother had had difficulties in school. A fourth unrelated boy was similarly affected. (Cohen (1993) referred to this as Jones syndrome. Not unexpectedly, at least one other disorder had been referred to as Jones syndrome (135550).)

Basel-Vanagaite et al. (2010) reported a nonconsanguineous family of Moroccan-Jewish origin with variable expression of ventriculomegaly or hydrocephalus and posterior fossa abnormalities. Two brothers had ventriculomegaly detected on brain imaging at ages 16 and 8 years, respectively. One also had a midline cyst in the trigeminal cistern and compressing the tectum, as well as a megacisterna magna with minimal vermian hypoplasia. He was asymptomatic and had normal neurologic development. The other boy had enlargement of all the ventricles and colpocephaly, as well as an enlarged posterior fossa with megacisterna magna, but no cyst. The massa intermedia was large and malformed, and he had partial absence of the septum pellucidum. He had recurrent headaches and underwent ventriculoperitoneal shunting. Otherwise he had normal development. The healthy mother had a history of 2 pregnancy terminations due to severe fetal hydrocephalus developing late in pregnancy; both were males. Her brain MRI showed enlargement of the lateral ventricles with mild colpocephaly, a midline cyst, an enlarged massa intermedia, and an enlarged posterior fossa with a megacisterna magna and minimal vermian hypoplasia. She had no neurologic abnormalities. The maternal grandmother had ventriculomegaly and recurrent headaches. She also had dysmetria of the upper limbs, abnormal tandem gait, and memory loss. Brain MRI of 2 clinically unaffected sisters of the probands showed mildly enlarged posterior fossa without ventricular dilatation. Basel-Vanagaite et al. (2010) noted that the Dandy-Walker malformation and megacisterna magna seem to represent a continuum of developmental anomalies of the posterior fossa, and that abnormalities of the posterior fossa predispose to the development of hydrocephalus.

Inheritance

Braddock et al. (1993) suggested autosomal dominant inheritance of sagittal craniosynostosis and Dandy-Walker malformation in the 4 cases they reported.

The transmission pattern of ventriculomegaly or hydrocephalus and posterior fossa abnormalities in the family reported by Basel-Vanagaite et al. (2010) was consistent with either autosomal dominant or X-linked inheritance.

Mapping

Vincent et al. (1994) described a contiguous gene syndrome resulting from deletion of 8q12.2-q21.2 (600257) and characterized by a combination of hydrocephalus with branchiootorenal (BOR) syndrome (113650), Duane syndrome (126800), and aplasia of the trapezius muscle. They suggested that a gene responsible for a dominant form of hydrocephalus maps within this region.