Disease expression in juvenile polyposis syndrome: A retrospective survey on a cohort of 221 European patients and comparison with a literature-derived cohort of 473 SMAD4/BMPR1A pathogenic variant carriers

Robert Blatter; Benjamin Tschupp; Stefan Aretz; Inge Bernstein; Chrystelle Colas; D Gareth Evans; Maurizio Genuardi; Frederik J. Hes; Robert Hüneburg; Heikki Järvinen; Fiona Lalloo; Gabriela Moeslein; Laura Renkonen-Sinisalo; Nicoletta Resta; Isabel Spier; Dora Varvara; Hans Vasen; Andrew R. Latchford; Karl Heinimann

Disease expression in juvenile polyposis syndrome: A retrospective survey on a cohort of 221 European patients and comparison with a literature-derived cohort of 473 SMAD4/BMPR1A pathogenic variant carriers

Robert Blatter, Benjamin Tschupp, Stefan Aretz, Inge Bernstein, Chrystelle Colas, D Gareth Evans, Maurizio Genuardi, Frederik J. Hes, Robert Hüneburg, Heikki Järvinen, Fiona Lalloo, Gabriela Moeslein, Laura Renkonen-Sinisalo, Nicoletta Resta, Isabel Spier, Dora Varvara, Hans Vasen, Andrew R. Latchford, Karl Heinimann

Division of Evolution, Infection and Genomics

Research output: Contribution to journal › Article › peer-review

Abstract

Purpose
Juvenile polyposis syndrome (JPS) is a rare, autosomal-dominantly inherited cancer predisposition caused in approximately 50% by pathogenic germline variants in SMAD4 and BMPR1A. We aimed to gather detailed clinical and molecular genetic information on JPS disease expression to provide a basis for management guidelines and establish open access variant databases.
Methods
We performed a retrospective, questionnaire-based European multi-centre survey on and established a cohort of SMAD4/BMPR1A pathogenic variant carriers from the medical literature.
Results
We analysed questionnaire-based data on 221 JPS patients (126 kindreds) from 10 European centres and retrieved literature-based information on 473 patients. Compared to BMPR1A carriers, SMAD4 carriers displayed twice as often anaemia (58% vs 26%), exclusively showed overlap symptoms with haemorrhagic telangiectasia (32%) and an increased prevalence (39% vs 13%) of gastric juvenile polyps. Cancer, reported in 15% of JPS patients (median age 41y), mainly occurred in the colorectum (overall: 62%, SMAD4: 58%, BMPR1A: 88%) and the stomach (overall: 21%; SMAD4: 27%, BMPR1A: 0%).
Conclusion
This comprehensive retrospective study on genotype-phenotype correlations in 694 JPS patients corroborates previous observations on JPS in general and SMAD4 carriers in particular, facilitates recommendations for clinical management and provides the basis for open access variant SMAD4 and BMPR1A databases.

Original language	English
Journal	Genetics in Medicine
Publication status	Accepted/In press - 27 Apr 2020

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Blatter, R., Tschupp, B., Aretz, S., Bernstein, I., Colas, C., Evans, D. G., Genuardi, M., Hes, F. J., Hüneburg, R., Järvinen, H., Lalloo, F., Moeslein, G., Renkonen-Sinisalo, L., Resta, N., Spier, I., Varvara, D., Vasen, H., Latchford, A. R., & Heinimann, K. (Accepted/In press). Disease expression in juvenile polyposis syndrome: A retrospective survey on a cohort of 221 European patients and comparison with a literature-derived cohort of 473 SMAD4/BMPR1A pathogenic variant carriers. Genetics in Medicine.

@article{c3056fb79cdb48bf844309d1e587913c,

title = "Disease expression in juvenile polyposis syndrome: A retrospective survey on a cohort of 221 European patients and comparison with a literature-derived cohort of 473 SMAD4/BMPR1A pathogenic variant carriers",

abstract = "PurposeJuvenile polyposis syndrome (JPS) is a rare, autosomal-dominantly inherited cancer predisposition caused in approximately 50% by pathogenic germline variants in SMAD4 and BMPR1A. We aimed to gather detailed clinical and molecular genetic information on JPS disease expression to provide a basis for management guidelines and establish open access variant databases.MethodsWe performed a retrospective, questionnaire-based European multi-centre survey on and established a cohort of SMAD4/BMPR1A pathogenic variant carriers from the medical literature.ResultsWe analysed questionnaire-based data on 221 JPS patients (126 kindreds) from 10 European centres and retrieved literature-based information on 473 patients. Compared to BMPR1A carriers, SMAD4 carriers displayed twice as often anaemia (58% vs 26%), exclusively showed overlap symptoms with haemorrhagic telangiectasia (32%) and an increased prevalence (39% vs 13%) of gastric juvenile polyps. Cancer, reported in 15% of JPS patients (median age 41y), mainly occurred in the colorectum (overall: 62%, SMAD4: 58%, BMPR1A: 88%) and the stomach (overall: 21%; SMAD4: 27%, BMPR1A: 0%).ConclusionThis comprehensive retrospective study on genotype-phenotype correlations in 694 JPS patients corroborates previous observations on JPS in general and SMAD4 carriers in particular, facilitates recommendations for clinical management and provides the basis for open access variant SMAD4 and BMPR1A databases.",

author = "Robert Blatter and Benjamin Tschupp and Stefan Aretz and Inge Bernstein and Chrystelle Colas and Evans, {D Gareth} and Maurizio Genuardi and Hes, {Frederik J.} and Robert H{\"u}neburg and Heikki J{\"a}rvinen and Fiona Lalloo and Gabriela Moeslein and Laura Renkonen-Sinisalo and Nicoletta Resta and Isabel Spier and Dora Varvara and Hans Vasen and Latchford, {Andrew R.} and Karl Heinimann",

year = "2020",

month = apr,

day = "27",

language = "English",

journal = "Genetics in Medicine",

issn = "1098-3600",

publisher = "Elsevier BV",

}

Blatter, R, Tschupp, B, Aretz, S, Bernstein, I, Colas, C, Evans, DG, Genuardi, M, Hes, FJ, Hüneburg, R, Järvinen, H, Lalloo, F, Moeslein, G, Renkonen-Sinisalo, L, Resta, N, Spier, I, Varvara, D, Vasen, H, Latchford, AR & Heinimann, K 2020, 'Disease expression in juvenile polyposis syndrome: A retrospective survey on a cohort of 221 European patients and comparison with a literature-derived cohort of 473 SMAD4/BMPR1A pathogenic variant carriers', Genetics in Medicine.

Disease expression in juvenile polyposis syndrome: A retrospective survey on a cohort of 221 European patients and comparison with a literature-derived cohort of 473 SMAD4/BMPR1A pathogenic variant carriers. / Blatter, Robert; Tschupp, Benjamin; Aretz, Stefan et al.
In: Genetics in Medicine, 27.04.2020.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Disease expression in juvenile polyposis syndrome

T2 - A retrospective survey on a cohort of 221 European patients and comparison with a literature-derived cohort of 473 SMAD4/BMPR1A pathogenic variant carriers

AU - Blatter, Robert

AU - Tschupp, Benjamin

AU - Aretz, Stefan

AU - Bernstein, Inge

AU - Colas, Chrystelle

AU - Evans, D Gareth

AU - Genuardi, Maurizio

AU - Hes, Frederik J.

AU - Hüneburg, Robert

AU - Järvinen, Heikki

AU - Lalloo, Fiona

AU - Moeslein, Gabriela

AU - Renkonen-Sinisalo, Laura

AU - Resta, Nicoletta

AU - Spier, Isabel

AU - Varvara, Dora

AU - Vasen, Hans

AU - Latchford, Andrew R.

AU - Heinimann, Karl

PY - 2020/4/27

Y1 - 2020/4/27

N2 - PurposeJuvenile polyposis syndrome (JPS) is a rare, autosomal-dominantly inherited cancer predisposition caused in approximately 50% by pathogenic germline variants in SMAD4 and BMPR1A. We aimed to gather detailed clinical and molecular genetic information on JPS disease expression to provide a basis for management guidelines and establish open access variant databases.MethodsWe performed a retrospective, questionnaire-based European multi-centre survey on and established a cohort of SMAD4/BMPR1A pathogenic variant carriers from the medical literature.ResultsWe analysed questionnaire-based data on 221 JPS patients (126 kindreds) from 10 European centres and retrieved literature-based information on 473 patients. Compared to BMPR1A carriers, SMAD4 carriers displayed twice as often anaemia (58% vs 26%), exclusively showed overlap symptoms with haemorrhagic telangiectasia (32%) and an increased prevalence (39% vs 13%) of gastric juvenile polyps. Cancer, reported in 15% of JPS patients (median age 41y), mainly occurred in the colorectum (overall: 62%, SMAD4: 58%, BMPR1A: 88%) and the stomach (overall: 21%; SMAD4: 27%, BMPR1A: 0%).ConclusionThis comprehensive retrospective study on genotype-phenotype correlations in 694 JPS patients corroborates previous observations on JPS in general and SMAD4 carriers in particular, facilitates recommendations for clinical management and provides the basis for open access variant SMAD4 and BMPR1A databases.

AB - PurposeJuvenile polyposis syndrome (JPS) is a rare, autosomal-dominantly inherited cancer predisposition caused in approximately 50% by pathogenic germline variants in SMAD4 and BMPR1A. We aimed to gather detailed clinical and molecular genetic information on JPS disease expression to provide a basis for management guidelines and establish open access variant databases.MethodsWe performed a retrospective, questionnaire-based European multi-centre survey on and established a cohort of SMAD4/BMPR1A pathogenic variant carriers from the medical literature.ResultsWe analysed questionnaire-based data on 221 JPS patients (126 kindreds) from 10 European centres and retrieved literature-based information on 473 patients. Compared to BMPR1A carriers, SMAD4 carriers displayed twice as often anaemia (58% vs 26%), exclusively showed overlap symptoms with haemorrhagic telangiectasia (32%) and an increased prevalence (39% vs 13%) of gastric juvenile polyps. Cancer, reported in 15% of JPS patients (median age 41y), mainly occurred in the colorectum (overall: 62%, SMAD4: 58%, BMPR1A: 88%) and the stomach (overall: 21%; SMAD4: 27%, BMPR1A: 0%).ConclusionThis comprehensive retrospective study on genotype-phenotype correlations in 694 JPS patients corroborates previous observations on JPS in general and SMAD4 carriers in particular, facilitates recommendations for clinical management and provides the basis for open access variant SMAD4 and BMPR1A databases.

M3 - Article

SN - 1098-3600

JO - Genetics in Medicine

JF - Genetics in Medicine

ER -