Relationship between sleep, sleep apnea, and neuropsychological function in children with Down syndrome.

PURPOSE: To determine whether sleep and sleep disordered breathing (SDB) contribute to the neuropsychological deficits of patients with Down syndrome, and whether treatment of SDB results in improvement in cognitive function. METHODS: In this cohort study, 25 children with Down syndrome underwent overnight polysomnography (PSG), Multiple Sleep Latency Testing (MSLT), and a battery of neuropsychological tests. Patients with SDB underwent a follow up PSG after treatment. All patients repeated the neuropsychological tests 13 months later. RESULTS: At baseline, there was no relationship between SDB and performance on the neuropsychological tests. However, total sleep time and sleep latency were related to tests of cognitive ability (p < 0.05) and comprehension (p < 0.01). The amount of time in slow-wave sleep correlated with tests of achievement (p < 0.01), and adaptive behavior (p < 0.01). Ten patients had SDB confirmed on PSG. Five of these patients were treated successfully with adenotonsillectomy and/or continuous positive airway pressure. The five who did not tolerate treatment were deficient in tests of adaptive behavior (Vineland p < 0.05) visual-motor integration (Beery p < 0.01) and achievement (Woodcock-Johnson p < 0.05) compared to those successfully treated. After treatment the patients improved in ratings of attention (Conners p < 0.05). CONCLUSIONS: Although SDB is common in children with Down syndrome, it is not a major contributor to their cognitive deficits. Cognitive function is related to the amount of sleep and particularly slow wave sleep. Successful treatment of SDB may improve their attention.

Acquired isochromosome 12p, somatic TP53 and PTEN mutations, and a germline ATM variant in an adolescent male with concurrent acute megakaryoblastic leukemia and mediastinal germ cell tumor.

Previous reports have described an association between hematologic malignancies (HMs) and extragonadal germ cell tumor (GCT). Most patients have been adolescent males with mediastinal nonseminomatous GCT. Although a variety of HMs have been reported, there is a striking predilection toward acute megakaryoblastic leukemia (AMKL). Shared cytogenetic anomalies--particularly isochromosome 12p [i(12p)]--have suggested common clonal origins to the tumors. We report the case of a 17-year-old boy presenting with AMKL and a synchronous mediastinal GCT, with the characteristic i(12p) in both neoplasms. The common clonal origin of the AMKL and GCT was further confirmed with massively parallel sequencing, which identified somatic TP53 and PTEN mutations, as well as a rare germline ATM variant. Although these represent commonly mutated genes in cancer, this combination of mutations is not typically associated with either GCT or AMKL, suggesting that these tumors may represent unique biologic entities when they co-occur.