Possibility of early diagnosis in a fetus affected by Prader‑Willi syndrome with maternal hetero‑UPD15: A lesson to be learned.

Prader‑Willi syndrome (PWS), a complicated neurodevelopmental disorder arising from errors in genomic imprinting, is characterized by evident hypotonia along with feeding difficulties and the absence of crying in early infancy. Hyperphagia and obesity are not uncommon in patients with PWS, usually accompanied by intellectual disability, cognitive impairment, short stature, small hands and feet, as well as hypogonadism and typical facial features. Due to the severe complications associated with PWS, a thorough understanding of its features and an early diagnosis, preferably in the fetal period, are important for clinical management. According to previous studies, prenatal diagnosis has been confirmed in only a few cases of PWS, using ultrasound, or as an accidental finding by cytogenetic molecular techniques, as no precise fetal phenotype has been defined. In this present study, an infant with PWS arising from maternal heterodisomy of chromosome 15 is described. This is a typical case of missed diagnosis by fetal ultrasound examination, chromosome karyotype analysis and chromosome microarray (CMA) conducted during the pregnancy. To delineate the complex prenatal characteristics of a fetus with PWS, prenatally‑diagnosed cases of PWS described in the literature were reviewed. This present study indicated that although prenatal signs are not sufficient for a diagnosis to be confirmed, a comprehensive consideration of these signs is important in leading to a diagnosis of suspected PWS, and thus prompts further prenatal investigations using molecular genetic tools. Furthermore, this present study also suggested that CMA can lead to a missed diagnosis of PWS/Angelman syndrome and other imprinting disorders despite its high value in the detection of copy‑number variants in individuals with developmental delay. If clinical signs strongly suggest PWS, other prenatal molecular genetic investigations, including methylation tests and short tandem repeat‑based linkage analysis for uniparental disomy, are recommended as an additional tool to aid diagnosis.