Tetrasomy 18p: report of cognitive and behavioral characteristics.

Our purpose was to describe intellectual and behavioral characteristics of persons with tetrasomy 18p. This is a more detailed investigation into the cognitive and behavioral characteristics of our previously reported tetrasomy 18p cohort of 43 plus six additional participants. We evaluated the intellectual functioning using standard measures of cognitive ability, measures of executive functioning, adaptive and maladaptive behaviors. Intellectual abilities ranged from mild impairment/borderline normal to severe/profound impairment calling into question the assumption that severe cognitive limitation is always a feature of tetrasomy 18p. For persons with tetrasomy 18p with mild cognitive deficits, the main barriers to successful functioning stems from limited social and metacognitive skill development and behavior regulation problems rather than being solely determined by cognitive deficits alone.

Mood disorders in individuals with distal 18q deletions.

We examined 36 participants at least 4 years old with hemizygous distal deletions of the long arm of Chromosome 18 (18q-) for histories of mood disorders and to characterize these disorders clinically. Since each participant had a different region of 18q hemizygosity, our goal was also to identify their common region of hemizygosity associated with mood disorders; thereby identifying candidate causal genes in that region. Lifetime mood and other psychiatric disorders were determined by semi-structured interviews of patients and parents, supplemented by reviews of medical and psychiatric records, and norm-referenced psychological assessment instruments, for psychiatric symptoms, cognitive problems, and adaptive functioning. Sixteen participants were identified with lifetime mood disorders (ages 12-42 years, 71% female, 14 having had unipolar depression and 2 with bipolar disorders). From the group of 20 who did not meet criteria for a mood disorder; a comparison group of 6 participants were identified who were matched for age range and deletion size. Mood-disordered patients had high rates of anxiety (75%) and externalizing behavior disorders (44%), and significant mean differences from comparison patients (P < 0.05), including higher overall and verbal IQs and lower autistic symptoms. A critical region was defined in the mood-disordered group that included a hypothetical gene, C18orf62, and two known genes, ZADH2 and TSHZ1. We conclude that patients having terminal deletions of this critical region of the long arm of Chromosome 18 are highly likely to have mood disorders, which are often comorbid with anxiety and to a lesser extent with externalizing disorders.