A diagnosis of Birt-Hogg-Dubé syndrome in individuals with Smith-Magenis syndrome: Recommendation for cancer screening

Cathy D Vocke; Leah R Fleming; Anna M Piskorski; Ali Amin; Chanika Phornphutkul; Suzanne de la Monte; Thierry Vilboux; Folami Duncan; Joan Pellegrino; Bonnie Braddock; Lindsay A Middelton; Laura S Schmidt; Maria J Merino; Edward W Cowen; Wendy J Introne; W Marston Linehan; Ann C M Smith

doi:10.1002/ajmg.a.63049

A diagnosis of Birt-Hogg-Dubé syndrome in individuals with Smith-Magenis syndrome: Recommendation for cancer screening

Am J Med Genet A. 2023 Feb;191(2):490-497. doi: 10.1002/ajmg.a.63049. Epub 2022 Dec 13.

Authors

Cathy D Vocke¹, Leah R Fleming^{2

3}, Anna M Piskorski⁴, Ali Amin⁴, Chanika Phornphutkul⁵, Suzanne de la Monte⁴, Thierry Vilboux^{2

6}, Folami Duncan^{2

7}, Joan Pellegrino⁸, Bonnie Braddock⁸, Lindsay A Middelton¹, Laura S Schmidt^{1

9}, Maria J Merino¹⁰, Edward W Cowen¹¹, Wendy J Introne², W Marston Linehan¹, Ann C M Smith²

Affiliations

¹ Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
² Office of the Clinical Director, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
³ Department of Genetics, Saint Luke's Genetics and Metabolic Clinic, Boise, Idaho, USA.
⁴ Department of Pathology, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
⁵ Division of Human Genetics, Department of Pediatrics, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
⁶ Medical Genetics Branch, National Human Genome Research Institute, NIH, Bethesda, Maryland, USA.
⁷ Department of Pediatric Emergency Medicine, Johns Hopkins Children's Center, Baltimore, Maryland, USA.
⁸ Medical Genetics, Upstate Medical University, Syracuse, New York, USA.
⁹ Basic Science Program, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
¹⁰ Laboratory of Pathology Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland, USA.
¹¹ Dermatology Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland, USA.

Abstract

We report a series of four unrelated adults with Smith-Magenis syndrome (SMS) and concomitant features of Birt-Hogg-Dubé (BHD) syndrome based upon haploinsufficiency for FLCN and characteristic renal cell carcinomas and/or evidence of cutaneous fibrofolliculomas. Three of the cases constitute the first known association of histopathologically verified characteristic BHD-associated renal tumors in adults with SMS; the fourth was identified to have histologically confirmed skin fibrofolliculomas. Molecular analysis documented second-hit FLCN mutations in two of the three cases with confirmed BHD renal pathology. These cases suggest the need to expand management recommendations for SMS to include kidney cancer surveillance starting at 20 years of age, as per the screening recommendations for BHD syndrome.

Keywords: Birt-Hogg-Dubé syndrome; FLCN; Smith-Magenis syndrome; cancer risk; cancer surveillance; del 17p11.2.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adult
Birt-Hogg-Dube Syndrome* / complications
Birt-Hogg-Dube Syndrome* / diagnosis
Birt-Hogg-Dube Syndrome* / genetics
Carcinoma, Renal Cell* / genetics
Early Detection of Cancer
Humans
Kidney Neoplasms* / genetics
Proto-Oncogene Proteins / genetics
Skin Neoplasms* / genetics
Smith-Magenis Syndrome* / complications
Tumor Suppressor Proteins / genetics

Substances

Proto-Oncogene Proteins
Tumor Suppressor Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding