Cognitive and behavioral features of Sturge-Weber syndrome, tuberous sclerosis, and neurofibromatosis are summarized by a literature review (113 references) at the New York University, New York. Sturge-Weber syndrome is associated with mental retardation in 50 to 60% of cases, correlated with the extent of unilateral cerebral calcification and atrophy. The occurrence of seizures in up to 90% of cases is associated with leptomeningeal angiomatosis, and predicts a poorer prognosis. Hemispherectomy provides an 80% rate of seizure freedom; mean age of surgery was 2 years for patients left with a mild disability compared to 3 years for those with moderate or severe disability. A progressive neurological and developmental deterioration may be explained by venous occlusions and hypoxia, and is sometimes correlated with a worsening of seizures and EEG abnormalities. Psychiatric symptoms in Sturge-Weber syndrome include irritability, social problems, ADHD, oppositional defiance disorder, self-abuse, aggressive behavior, and depression, often correlated with occurrence of seizures.

Tuberous sclerosis (TS) presents with seizures in 80 - 90% of cases, often developing in the first year of life, and manifesting as infantile spasms in one-third. An IQ below 70 was found in 44% of one sample of 108 patients (a DQ below 21 in 31%); 55% had a normal IQ. In studies of children with TS and near-normal IQ, 50% had ADD or hyperkinetic syndrome, and 25% had ODD. Infantile spasms and low IQ are significantly related. Cognition is also correlated with tuber burden (tuber number, size, and location). Genetic factors correlate with developmental outcome: TSC1 cases have lower rates of mental retardation, seizures, and autism than TSC2. TS is linked to autistic spectrum disorder in 50 to 60% of cases (the rate is higher in those with infantile spasms), and these patients do not show the characteristic male preponderance seen in idiopathic autism cases. Temporal lobe tubers and EEG abnormalities increase the risk of autism.

Neurofibromatosis type 1 (NF-1) patients have an average mean IQ, despite earlier reports of an increased incidence of mental retardation, but learning disabilities, especially visual-perceptual deficits, occur in 30-60% of cases. ADHD is reported in 33%. Some studies show a resolution of childhood cognitive dysfunction in adults with NF-1. Cognitive deficits are correlated with the occurrence, number, and location of UBO’s. Macrocephaly shows no correlation with cognitive functioning in NF-1. Adolescents with NF-1 and learning difficulties had social-skill problems, when compared to unaffected siblings. ADHD was the major risk factor for social problems. [1]

COMMENT. Neurocutaneous syndromes are associated with an increased rate of mental retardation or learning disabilities. Problems in cognition and behavior are related to the underlying neurological disorders, especially seizures, and in tuberous sclerosis the genotype contributes to clinical heterogeneity. An increased prevalence of ADHD in all three syndromes is noteworthy, and tuberous sclerosis is strongly linked with autism.