Prenatal features in Beckwith-Wiedemann syndrome and indications for prenatal testing

• Published in: Journal of medical genetics Vol. 58; no. 12; pp. 842 - 849
• Main Authors: Carli, Diana, Bertola, Chiara, Cardaropoli, Simona, Ciuffreda, Valentina Pia, Pieretto, Marta, Ferrero, Giovanni Battista, Mussa, Alessandro
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group Ltd 01.12.2021; BMJ Publishing Group LTD
• Subjects: Adult; Beckwith-Wiedemann syndrome; Beckwith-Wiedemann Syndrome - diagnosis; Beckwith-Wiedemann Syndrome - genetics; Child; Child, Preschool; Chromosome Aberrations; Couples; Cysts; Data collection; Developmental defects; DNA methylation; Dysplasia; Enlargement; Female; Femur; Fertility; Genetic Association Studies - methods; Genotype & phenotype; Gestational Age; gynecology; Health care; Humans; Hypertension; Infant; Male; Mesenchyme; obstetrics; Ovaries; Patients; Pediatrics; Phenotypes; Pituitary (anterior); Placenta - metabolism; Pregnancy; pregnancy tests; Prenatal Diagnosis - methods; Reproduction; Reproductive health; reproductive medicine; Sperm; Ultrasonography, Prenatal - methods; α-Fetoprotein; gynecology; DNA methylation; reproductive medicine; obstetrics; pregnancy tests
• ISSN: 0022-2593; 1468-6244
• DOI: 10.1136/jmedgenet-2020-107311

BackgroundMost cases of Beckwith-Wiedemann spectrum (BWSp) are diagnosed after birth and few studies evaluated the prenatal phenotype; here, we investigate these aspects in a large series of patients with BWSp.MethodsEighty-nine patients with BWSp recruited through the BWSp Internal Registry of the Pediatric Genetics Unit of the Regina Margherita Children’s Hospital of Torino and through the Italian Association of Patients with BWSp. Data collection was conducted through administration of a personalised questionnaire, interview to patients’ parents, review of the clinical records, including prenatal ultrasound (US) and biochemical screening tests, physical examination and review of clinical and molecular data of the patients.ResultsSeventeen patients (19.1%) were conceived through assisted reproductive techniques (ART). Twinning occurred in nine pregnancies (three from ART). Pregnancy biochemical screening tests showed increased alpha-fetoprotein (1.52±0.79 multiples of median (MoM), p=0.001), uEstriol (1.37±0.38 MoM, p<0.001) and total human chorionic gonadotrophin (2.14±2.12 MoM, p=0.008) at 15–18 weeks (n=28). Morphology US scan revealed abdominal and head circumferences higher than normal (1.42±1.10 SD scores, p<0.001 and 0.54±0.88, p<0.001, respectively) with normal femur lengths. Sixty-four cases (71.9%%) had a various combination of US findings, including macrosomia (n=32), omphalocele (n=15), enlargement of abdominal organs (n=6), macroglossia (n=11), adrenal cysts/masses (n=2), nephroureteral anomalies (n=11), polyhydramnios (n=28), placental enlargement (n=2) or mesenchymal dysplasia (n=4).ConclusionWe propose a clinical scoring system for prenatal molecular investigations defining major, minor and supportive criteria among the several features often observed prenatally in BWSp.