Endocrine Society, San Francisco, California. June 15-18, 2008
Abstract title:
Childhood Stature in WAGR Syndrome
Abstract number: P2-576
Abstract link: Full Text
http://www.abstracts2view.com/endo/view.php?nu=ENDO08L_P2-576
Conference link: http://www.endo-society.org/endo/index.cfm
Childhood Stature in WAGR Syndrome
RL Levinn, JC Han, CA Wijesinghe, JK Gustafson, JM Checchi, DC Adler-Wailes, KS Jefferson-George, OM Rennert, JA Yanovski, Unit on Growth & Obesity, PDEGEN, NICHD, NIH, Bethesda, MD
Background: WAGR syndrome (Wilms tumor, Aniridia, Genitourinary anomalies, mental Retardation) is a rare genetic disorder caused by heterozygous contiguous gene deletions of variable size at Chromosome 11p13. Short stature has been observed in case reports, but not longitudinally studied.
Objective: To assess stature during childhood in subjects with WAGR syndrome.
Design/Method: Anthropometric measurements were obtained from medical records of 40 subjects with WAGR syndrome, and Z-scores calculated using CDC 2000 and NHANES II data. Individual height-Z (HtZ) was averaged from all measurements within a specified age range. Growth velocity-Z (GVZ) was computed from the slope of the best-fit line of heights between ages 2.5-9y. HtZ was compared to population mean (one-sample T-test vs. 0) and mid-parental height-Z (MPHZ) (paired-samples T-test). 20 subjects with WAGR syndrome and 20 healthy controls (matched for age, sex, race, BMI) were also compared for differences in IGF-1. Deletion size was determined by oligo microarray comparative genomic hybridization.
Results: All subjects had normal birth length (mean SD: 49.9 2.8cm) and pre-pubertal GVZ (0.080.68), but postnatal HtZ was lower than population mean and MPHZ for ages 2-20y (Figure 1). HtZ at 17-20y was negatively associated with size of deletion ( = -0.90, p<0.001). Every 1Mb increase in deletion size predicted a decrease in final HtZ by 0.13. There was no significant difference between IGF-1 in WAGR subjects and controls (232139 vs. 286187, p=0.43). Neither HtZ nor GVZ was significantly associated with IGF-1, or with history of Wilms tumor. Based on parental report, average age of pubarche in males was 11.31.7y, and menarche in females 11.91.6y.
Discussion: Children with WAGR syndrome have postnatal short stature that is modest in early childhood and more pronounced post-pubertally, with lower final HtZ associated with larger deletions. Normal IGF-1 and pre-pubertal GVZ do not suggest growth hormone insufficiency. Inadequate pubertal growth spurt in the setting of non-delayed or slightly advanced puberty may contribute to decreased final height in patients with WAGR syndrome.
DISCLOSURE: Yanovski, JA: Principal Investigator, Roche Pharmaceuticals; Principal Investigator, O.N. Diagnostics, LLC, Obecure; Investigator, Abbott Laboratories.
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