ESPE Abstracts

Introduction: Prader-Willi syndrome (PWS) is a rare genetic disorder resulting from the lack of expression of the PWS region (locus q11-q13) on the paternally derived chromosome 15. Either a paternal deletion of the PWS region (50%), a maternal uniparental disomy (mUPD; 43%), an imprinting defect (4.1%) or translocation (<1%) can lead to PWS. Deletions are almost always de novo and manifest either as a large type I or a smaller type II deletion. In more rare cases, atypical deletions are identified, smaller or larger than the typical deletions and with different breakpoints. These patients may show distinct phenotypical features. In this study, we report 8 patients with atypical deletions from our Dutch PWS cohort, which provide further information for unravelling the mystery of the genotype-phenotype correlations in PWS.

Methods: This was a prospective study in 8 patients with an atypical deletion in the PWS region. All patients are treated with growth hormone and regularly visit the Dutch Reference Center for Prader-Willi syndrome.

Results: All patients (6 males, 2 females) had a different atypical deletion. One patient had two separate deletions in the PWS critical region. The median (IQR) of the age at diagnosis was 9.7 (0.8; 23.7) months. Cryptorchidism was present in all males and 62.5% of the patients required tube feeding after birth. At the last examination, the median (IQR) age was 12.0 (5.4; 24.1) years. Hyperphagia was present in 50% of the patients and 75% had typical facial features. Three patients (37.5%) had another endocrine condition and 4 (50%) had scoliosis. IQ varied widely amongst the patients and four patients (50%) had intellectual disability (IQ<70) and 6 (75%) had developmental delay.

Conclusions: We report 8 patients with an atypical microdeletion in the PWS critical region. All patients had symptoms of Prader-Willi syndrome, but there were patients that did not show some of the core features, such as neonatal feeding difficulties, typical facial features, intellectual disability, hyperphagia and obesity. Our findings further advance the knowledge of and insight in genotype-phenotype correlations in PWS.