Hereditary neurocutaneous angiomatosis. Report of four cases

The authors report the coexistence of vascular nevi (hemangiomas and arteriovenous malformations (AVMs) of the skin) with AVMs and venous malformations of the brain in male siblings from two related but nonconsanguineous families of three generations. The proband, his siblings, parents, aunts, uncles, and cousins were examined, underwent magnetic resonance (MR) imaging and MR angiography, and when appropriate, cerebral angiography. A father had vascular nevi and a mother, his sister, had an azygos anterior cerebral artery. No other cutaneous or cerebrovascular malformations were present in the parents. Each of the two families had two boys and one girl, 9 to 18 years of age. All the children had vascular nevi and all of the boys had coexisting cerebrovascular malformations: AVMs in three, and a venous malformation in another. One boy had three cerebral AVMs. Two boys had a cerebral hemorrhage, and one also had focal motor seizures. The skin lesions were not those of the Sturge-Weber-Dimitri, Rendu-Osler-Weber, or Wybum-Mason syndromes. The association of cutaneous and cerebrovascular malformations was seen only in males in these families. but females have also been reported in the literature. The results obtained in these families and three other families reported from Western and Central Europe indicate that the association of cerebral and cutaneous vascular hamartomas constitutes a distinct, hereditary clinicopathological entity with autosomal dominant inheritance and variable penetrance. The clinical manifestations of this syndrome are visible, painful vascular nevi, epilepsy, cerebral hemorrhage, and focal neurological deficits. The preponderance of male patients with the full expression of the syndrome suggests a possible hormonal influence on the expression of the gene.