ESPE Abstracts

Background: Prader–Willi syndrome (PWS) is caused by absence of expression of imprinted genes on the paternal chromosome 15 (15q11.2–q13) due to a paternal deletion, maternal uniparental disomy 15 and rarely an imprinting defect. The clinical signs of PWS are hypotonia, muscle weakness, excessive eating, morbid obesity, delayed global development, hypogonadism, and short stature. Marfan syndrome is caused by mutations in the FBN1 gene, located on chromosome 15 (15q21.1), inherited in an autosomal dominant manner. It is a connective tissue disorder with cardinal features in the ocular, skeletal, and cardiovascular system.

Case presentation: A 16-year-old boy with PWS, based on maternal uniparental disomy, showed more severe hypotonia, and muscle weakness compared to other children with PWS. He had myopia (−2.5) and a striking stature with a relatively low BMI (16.8 kg/m²; −1 S.D.), a flat thorax, scoliosis, and increased joint laxity (a picture of the patient will be included in the presentation). The arm/height ratio was normal (1.02). DNA investigation showed a homozygous mutation (c.4075A>G, p.Ile1359Val) in the FBN1 gene. Opthalmological and cardiological screening revealed no abnormalities. His systemic score (Ghent criteria for Marfan syndrome) was 3, based on positive thumb sign, scoliosis, and pes plani. His mother carried the same FBN1 mutation, in heterozygous state. She had no marfanoid features. The pathogenicity of this variant is yet unknown. Considering the presentation of our patient we suspect that in the homozygous state it may lead to a marfanoid phenotype. Both mother and son will be investigated regularly in our Marfan clinic.

Conclusion: Uniparental disomy increases the likelihood of diseases due to recessive or mild dominant mutations. An abnormal presentation of a known disease could be a trigger for the search of a second genetic disorder.