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

Andrea Gazzin, Diana Carli, Fabio Sirchia, Cristina Molinatto, Simona Cardaropoli, Giuseppe Palumbo, Giuseppe Zampino, Giovanni Battista Ferrero, Alessandro Mussa

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1691-1702
Number of pages12
JournalAmerican journal of medical genetics. Part A
Volume179
Issue number9
DOIs
Publication statusPublished - Sep 2019

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Beckwith-Wiedemann Syndrome
Phenotype
Health
Sertoli Cell Tumor
Macroglossia
Pediatrics
Swallows
Hepatoblastoma
Neoplasms
Myoma
Azoospermia
Assisted Reproductive Techniques
Pancreatectomy
Cryptorchidism
Urolithiasis
Asphyxia
Testicular Neoplasms
Hyperinsulinism
Scoliosis
Hemangioma

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Phenotype evolution and health issues of adults with Beckwith-Wiedemann syndrome. / Gazzin, Andrea; Carli, Diana; Sirchia, Fabio; Molinatto, Cristina; Cardaropoli, Simona; Palumbo, Giuseppe; Zampino, Giuseppe; Ferrero, Giovanni Battista; Mussa, Alessandro.

In: American journal of medical genetics. Part A, Vol. 179, No. 9, 09.2019, p. 1691-1702.

Research output: Contribution to journalArticle

Gazzin, Andrea ; Carli, Diana ; Sirchia, Fabio ; Molinatto, Cristina ; Cardaropoli, Simona ; Palumbo, Giuseppe ; Zampino, Giuseppe ; Ferrero, Giovanni Battista ; Mussa, Alessandro. / Phenotype evolution and health issues of adults with Beckwith-Wiedemann syndrome. In: American journal of medical genetics. Part A. 2019 ; Vol. 179, No. 9. pp. 1691-1702.
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title = "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.",
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T1 - Phenotype evolution and health issues of adults with Beckwith-Wiedemann syndrome

AU - Gazzin, Andrea

AU - Carli, Diana

AU - Sirchia, Fabio

AU - Molinatto, Cristina

AU - Cardaropoli, Simona

AU - Palumbo, Giuseppe

AU - Zampino, Giuseppe

AU - Ferrero, Giovanni Battista

AU - Mussa, Alessandro

N1 - © 2019 Wiley Periodicals, Inc.

PY - 2019/9

Y1 - 2019/9

N2 - 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.

AB - 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.

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DO - 10.1002/ajmg.a.61301

M3 - Article

VL - 179

SP - 1691

EP - 1702

JO - American Journal of Medical Genetics, Part A

JF - American Journal of Medical Genetics, Part A

SN - 1552-4825

IS - 9

ER -