Beneficial effects of growth hormone treatment on cognition in children with Prader-Willi syndrome: a randomized controlled trial and longitudinal study.

BACKGROUND: Knowledge about the effects of GH treatment on cognitive functioning in children with Prader-Willi syndrome (PWS) is limited. METHODS: Fifty prepubertal children aged 3.5 to 14 yr were studied in a randomized controlled GH trial during 2 yr, followed by a longitudinal study during 4 yr of GH treatment. Cognitive functioning was measured biennially by short forms of the WPPSI-R or WISC-R, depending on age. Total IQ (TIQ) score was estimated based on two subtest scores. RESULTS: During the randomized controlled trial, mean sd scores of all subtests and mean TIQ score remained similar compared to baseline in GH-treated children with PWS, whereas in untreated controls mean subtest sd scores and mean TIQ score decreased and became lower compared to baseline. This decline was significant for the Similarities (P = 0.04) and Vocabulary (P = 0.03) subtests. After 4 yr of GH treatment, mean sd scores on the Similarities and Block design subtests were significantly higher than at baseline (P = 0.01 and P = 0.03, respectively), and scores on Vocabulary and TIQ remained similar compared to baseline. At baseline, children with a maternal uniparental disomy had a significantly lower score on the Block design subtest (P = 0.01) but a larger increment on this subtest during 4 yr of GH treatment than children with a deletion. Lower baseline scores correlated significantly with higher increases in Similarities (P = 0.04) and Block design (P < 0.0001) sd scores. CONCLUSIONS: Our study shows that GH treatment prevents deterioration of certain cognitive skills in children with PWS on the short term and significantly improves abstract reasoning and visuospatial skills during 4 yr of GH treatment. Furthermore, children with a greater deficit had more benefit from GH treatment.

Efficacy and safety of long-term continuous growth hormone treatment in children with Prader-Willi syndrome.

BACKGROUND: Children with Prader-Willi syndrome (PWS) have abnormal body composition and impaired growth. Short-term GH treatment has beneficial effects. OBJECTIVES: The aim of the study was to investigate effects of long-term continuous GH treatment on body composition, growth, bone maturation, and safety parameters. SETTING: We conducted a multicenter prospective trial. DESIGN: Fifty-five children with a mean +/- sd age of 5.9 +/- 3.2 yr were followed during 4 yr of continuous GH treatment (1 mg/m(2) . d). Data were annually obtained in one center: fat percentage (fat%) and lean body mass (LBM) by dual-energy x-ray absorptiometry, height, weight, head circumference, bone age, blood pressure, and fasting IGF-I, IGF binding protein-3, glucose, insulin, glycosylated hemoglobin, total cholesterol, high-density lipoprotein, and low-density lipoprotein. sd scores (SDS) were calculated according to Dutch and PWS reference values (SDS and SDS(PWS)). RESULTS: Fat%SDS was significantly lower after 4 yr of GH treatment (P < 0.0001). LBMSDS significantly increased during the first year (P = 0.02) but returned to baseline values the second year and remained unchanged thereafter. Mean +/- sd height normalized from -2.27 +/- 1.2 SDS to -0.24 +/- 1.2 SDS (P < 0.0001). Head circumference SDS increased from -0.79 +/- 1.0 at start to 0.07 +/- 1.1 SDS after 4 yr. BMISDS(PWS) significantly decreased. Mean +/- sd IGF-I and the IGF-I/IGF binding protein-3 ratio significantly increased to 2.08 +/- 1.1 and 2.32 +/- 0.9 SDS, respectively. GH treatment had no adverse effects on bone maturation, blood pressure, glucose homeostasis, and serum lipids. CONCLUSIONS: Our study in children with PWS shows that 4 yr of continuous GH treatment (1 mg/m(2) . d) improves body composition by decreasing fat%SDS and stabilizing LBMSDS and head circumference SDS and normalizes heightSDS without adverse effects. Thus, long-term continuous GH treatment is an effective and safe therapy for children with PWS.

Dandy-Walker complex in a boy with a 5 Mb deletion of region 1q44 due to a paternal t(1;20)(q44;q13.33).

A 10-year-old boy with vermis hypoplasia, dilatation of the fourth ventricle, enlarged cisterna magna and aplasia of the corpus callosum, consistent with the Dandy-Walker complex (DWC), and slight facial dysmorphisms, severe motor and mental retardation is presented. By combining data obtained by karyotyping, array-CGH, FISH, and multiplex ligation-mediated probe amplification (MLPA) we identified a 5 Mb deletion of the 1q44 --> qter region resulting from a paternal t(1;20)(q44;q13.33). This smallest 1q44 deletion reported so far, enabled us to significantly narrow down the number of candidate genes for the DWC in this region. Since the ZNF124 transcription factor is strongly expressed in the fetal brain it may represent a candidate gene for the DWC at 1q44.