Appreciating the broad clinical features of SMAD4 mutation carriers: A multicenter chart review

Karen E. Wain, Marissa S. Ellingson, Jamie McDonald, Amanda Gammon, Maegan Roberts, Pavel Pichurin, Ingrid Winship, Douglas L. Riegert-Johnson, Jeffrey N. Weitzel, Noralane Morey Lindor

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Heterozygous loss-of-function SMAD4 mutations are associated with juvenile polyposis syndrome and hereditary hemorrhagic telangiectasia. Some carriers exhibit symptoms of both conditions, leading to juvenile polyposis-hereditary hemorrhagic telangiectasia syndrome. Three families have been reported with connective tissue abnormalities. To better understand the spectrum and extent of clinical findings in SMAD4 carriers, medical records of 34 patients (20 families) from five clinical practices were reviewed. Twenty-one percent of the patients (7/34) had features suggesting a connective tissue defect: enlarged aortic root (n = 3), aortic and mitral insufficiency (n = 2), aortic dissection (n = 1), retinal detachment (n = 1), brain aneurysms (n = 1), and lax skin and joints (n = 1). Juvenile polyposis-specific findings were almost uniformly present but variable. Ninety-seven percent of the patients had colon polyps that were generally pan-colonic and of variable histology and number. Forty-eight percent of the patients (15/31) had extensive gastric polyposis. Hereditary hemorrhagic telangiectasia features, including epistaxis (19/31, 61%), mucocutaneous telangiectases (15/31, 48%), liver arteriovenous malformation (6/16, 38%), brain arteriovenous malformation (1/26, 4%), pulmonary arteriovenous malformation (9/17, 53%), and intrapulmonary shunting (14/23, 61%), were documented in 76% of the patients. SMAD4 carriers should be managed for juvenile polyposis and hereditary hemorrhagic telangiectasia because symptoms of both conditions are likely yet unpredictable. Connective tissue abnormalities are an emerging component of juvenile polyposis-hereditary hemorrhagic telangiectasia syndrome, and larger studies are needed to understand these manifestations.

Original languageEnglish (US)
Pages (from-to)588-593
Number of pages6
JournalGenetics in Medicine
Volume16
Issue number8
DOIs
StatePublished - 2014

Fingerprint

Arteriovenous Malformations
Mutation
Connective Tissue
Hereditary Hemorrhagic Telangiectasia
Telangiectasis
Epistaxis
Mitral Valve Insufficiency
Intracranial Aneurysm
Retinal Detachment
Polyps
Medical Records
Dissection
Histology
Colon
Joints
Lung
Skin
Liver
Brain
Juvenile Polyposis with Hereditary Hemorrhagic Telangiectasia

Keywords

  • connective tissue
  • HHT
  • JP
  • SMAD4

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Appreciating the broad clinical features of SMAD4 mutation carriers : A multicenter chart review. / Wain, Karen E.; Ellingson, Marissa S.; McDonald, Jamie; Gammon, Amanda; Roberts, Maegan; Pichurin, Pavel; Winship, Ingrid; Riegert-Johnson, Douglas L.; Weitzel, Jeffrey N.; Lindor, Noralane Morey.

In: Genetics in Medicine, Vol. 16, No. 8, 2014, p. 588-593.

Research output: Contribution to journalArticle

Wain, KE, Ellingson, MS, McDonald, J, Gammon, A, Roberts, M, Pichurin, P, Winship, I, Riegert-Johnson, DL, Weitzel, JN & Lindor, NM 2014, 'Appreciating the broad clinical features of SMAD4 mutation carriers: A multicenter chart review', Genetics in Medicine, vol. 16, no. 8, pp. 588-593. https://doi.org/10.1038/gim.2014.5
Wain, Karen E. ; Ellingson, Marissa S. ; McDonald, Jamie ; Gammon, Amanda ; Roberts, Maegan ; Pichurin, Pavel ; Winship, Ingrid ; Riegert-Johnson, Douglas L. ; Weitzel, Jeffrey N. ; Lindor, Noralane Morey. / Appreciating the broad clinical features of SMAD4 mutation carriers : A multicenter chart review. In: Genetics in Medicine. 2014 ; Vol. 16, No. 8. pp. 588-593.
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