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.

Cancer incidence and spectrum among children with genetically confirmed Beckwith-Wiedemann spectrum in Germany: a retrospective cohort study

“…Notably, new evidence does support an increase in cancer risk for BWSp beyond childhood. 25 (3) We did not have access to patient medical records, and thus could not determine each subject’s age or date at clinical syndrome diagnosis in case this age differed from the molecular diagnosis. It is likely that, in some instances, the BWSp diagnosis was prompted by the development of a childhood cancer.…”

Investigation of (epi)genotype causes and follow‐up manifestations in the patients with classical and atypical phenotype ofBeckwith‐Wiedemannspectrum

“…They stated that during this early period the face was round to oval with prominent cheeks, and emphasized that the typical facial appearance improved as the age got older. However, Gazzin, et al (2019) evaluated adult BWS patients, and showed prognathism in their photographs. In the patients presented here with classical phenotype, while coarse face with prominent cheeks and micrognathia were noticeable in IC1 subgroup, IC2 subgroup showed a round face, prominent cheeks, micrognathia, severe macroglossia, facial naevus simplex, and ear creases.…”

Hepatocellular Carcinoma in a 24-Year-Old Female with Beckwith–Wiedemann Syndrome: A Case Report and Review of the Literature

“…[ 1 ] Overall, the oncologic risk is highest for patients with BWS in the first two years of life, [ 1 ] and after ten years of age, the tumor risk approaches that of the general population. [ 6 ] There is no evidence of an increased risk of malignant tumors in adults with BWS, [ 1 ] although hepatoblastoma, acute lymphoblastic leukemia, adrenal adenoma, testicular Sertoli cell tumor, and three benign tumors (hepatic hemangioma, uterine myoma, and mammary fibroepithelioma) have been reported in young adults with BWS [ 7 ].…”