Phenotypic subtypes in attention deficit hyperactivity disorder in an isolated population.
Croes EA., El Galta R., Houwing-Duistermaat JJ., Ferdinand RF., López León S., Rademaker TAM., Dekker MCJ., Oostra BA., Verhulst F., Van Duijn CM.
We address the use of two informants in genetic studies and whether familial aggregation is similar for the three phenotypic subtypes of ADHD. Lifetime ADHD was diagnosed in a Dutch isolated population using parents and teachers as informants, creating two subgroups (one or two informants), then further divided into three phenotypic categories (inattentive, hyperactive/impulsive, combined). Genealogy was collected for all patients. Mean kinship coefficients for the subgroups were calculated. Fifteen of 26 children were linked to a common ancestor within 10 generations. The mean kinship coefficient of patients confirmed by two informants was significantly higher than in patients only scored positive by one informant (p = 0.03). All patients of the inattentive subtype were connected to a common ancestor, which was significantly higher (p = 0.03) than expected. Eighty-one percent of these patients derive of consanguineous marriages, also higher than expected. This means that recessive mutations may be involved in the inattentive subtype. These patients were more closely related than those with the other phenotypes (p<0.01). Our data suggests that using two informants in diagnosing ADHD helps identify a phenotype with a strong genetic component. The inattentive phenotype showed strong familial clustering and evidence of a recessive origin.