Phenotype evolution and health issues of adults with Beckwith-Wiedemann syndrome.

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.

• Authors: Andrea Gazzin, Diana Carli, Fabio Sirchia, Cristina Molinatto, Simona Cardaropoli, Giuseppe Palumbo, Giuseppe Zampino, Giovanni Battista Ferrero, Alessandro Mussa
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 179 Issue 9 Pg. 1691-1702 (09 2019) ISSN: 1552-4833 [Electronic] United States
• PMID: 31339634 (Publication Type: Journal Article)
• Copyright: © 2019 Wiley Periodicals, Inc.

Topics

• Adolescent
• Adult
• Beckwith-Wiedemann Syndrome (complications, genetics, physiopathology)
• DNA Methylation (genetics)
• Female
• Genomic Imprinting (genetics)
• Hepatoblastoma (etiology, genetics, physiopathology)
• Humans
• Male
• Middle Aged
• Neoplasms (etiology, genetics, physiopathology)
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (etiology, genetics, physiopathology)
• Sertoli Cell Tumor (etiology, genetics, physiopathology)
• Wilms Tumor (etiology, genetics, physiopathology)
• Young Adult