Andrea Gazzin1, Diana Carli1, Fabio Sirchia2, Cristina Molinatto1, Simona Cardaropoli1, Giuseppe Palumbo3, Giuseppe Zampino4, Giovanni Battista Ferrero1, Alessandro Mussa1. 1. Department of Public Health and Pediatrics, University of Torino, Torino, Italy. 2. Institute for Maternal Child Health IRCCS "Burlo Garofolo", Trieste, Italy. 3. Department of Haematology, Bambino Gesù Hospital, Rome, Italy. 4. Department of Woman and Child Health, Center for Rare Diseases and Birth Defects, Institute of Pediatrics, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy.
Abstract
BACKGROUND: Beckwith-Wiedemann syndrome (BWS) phenotype usually mitigates with age and data on adulthood are limited. Our study aims at reporting phenotype evolution and health issues in adulthood. METHODS: 34 patients (16 males), aged 18-58 years (mean 28.5) with BWS were enrolled. RESULTS: 26 patients were molecularly confirmed, 5 tested negative, and 3 were not tested. Final tall stature was present in 44%. Four patients developed Wilms' Tumor (2, 3, 5, and 10 years, respectively); one hepatoblastoma (22 years); one acute lymphoblastic leukemia (21 years); one adrenal adenoma and testicular Sertoli cell tumor (22 and 24 years, respectively); and three benign tumors (hepatic haemangioma, uterine myoma, and mammary fibroepithelioma). Surgery for BWS-related features was required in 85%. Despite surgical correction several patients presented morbidity and sequelae of BWS pediatric issues: pronunciation/swallow difficulties (n = 9) due to macroglossia, painful scoliosis (n = 4) consistent with lateralized overgrowth, recurrent urolithiasis (n = 4), azoospermia (n = 4) likely consequent to cryptorchidism, severe intellectual disability (n = 2) likely related to neonatal asphyxia and diabetes mellitus (n = 1) due to subtotal pancreatectomy for intractable hyperinsulinism. Four patients (two males) had healthy children (three physiologically conceived and one through assisted reproductive technology). CONCLUSIONS: Adult health conditions in BWS are mostly consequent to pediatric issues, underlying the preventive role of follow-up strategies in childhood. Malignancy rate observed in early adulthood in this small cohort matches that observed in the first decade of life, cumulatively raising tumor rate in BWS to 20% during the observation period. Further studies are warranted in this direction.
BACKGROUND:Beckwith-Wiedemann syndrome (BWS) phenotype usually mitigates with age and data on adulthood are limited. Our study aims at reporting phenotype evolution and health issues in adulthood. METHODS: 34 patients (16 males), aged 18-58 years (mean 28.5) with BWS were enrolled. RESULTS: 26 patients were molecularly confirmed, 5 tested negative, and 3 were not tested. Final tall stature was present in 44%. Four patients developed Wilms' Tumor (2, 3, 5, and 10 years, respectively); one hepatoblastoma (22 years); one acute lymphoblastic leukemia (21 years); one adrenal adenoma and testicular Sertoli cell tumor (22 and 24 years, respectively); and three benign tumors (hepatic haemangioma, uterine myoma, and mammary fibroepithelioma). Surgery for BWS-related features was required in 85%. Despite surgical correction several patients presented morbidity and sequelae of BWS pediatric issues: pronunciation/swallow difficulties (n = 9) due to macroglossia, painful scoliosis (n = 4) consistent with lateralized overgrowth, recurrent urolithiasis (n = 4), azoospermia (n = 4) likely consequent to cryptorchidism, severe intellectual disability (n = 2) likely related to neonatal asphyxia and diabetes mellitus (n = 1) due to subtotal pancreatectomy for intractable hyperinsulinism. Four patients (two males) had healthy children (three physiologically conceived and one through assisted reproductive technology). CONCLUSIONS: Adult health conditions in BWS are mostly consequent to pediatric issues, underlying the preventive role of follow-up strategies in childhood. Malignancy rate observed in early adulthood in this small cohort matches that observed in the first decade of life, cumulatively raising tumor rate in BWS to 20% during the observation period. Further studies are warranted in this direction.
Authors: Kelly A Duffy; Christopher M Cielo; Jennifer L Cohen; Christina X Gonzalez-Gandolfi; Jessica R Griff; Evan R Hathaway; Jonida Kupa; Jesse A Taylor; Kathleen H Wang; Arupa Ganguly; Matthew A Deardorff; Jennifer M Kalish Journal: Am J Med Genet C Semin Med Genet Date: 2019-08-30 Impact factor: 3.908
Authors: Patrizia Defabianis; Alessandro Mussa; Rossella Ninivaggi; Diana Carli; Federica Romano Journal: Int J Environ Res Public Health Date: 2022-02-20 Impact factor: 3.390