The University of Southampton
University of Southampton Institutional Repository

Clinical features in a family with an R460H mutation in transforming growth factor receptor 2 gene

Clinical features in a family with an R460H mutation in transforming growth factor receptor 2 gene
Clinical features in a family with an R460H mutation in transforming growth factor receptor 2 gene
OBJECTIVES:
To describe the clinical findings and natural history in 22 carriers of an R460H mutation in the transforming growth factor beta receptor 2 gene (TGFbetaR2) from a five-generation kindred ascertained by familial aortic dissection.
METHODS:
13 of the confirmed carriers were interviewed and examined, and information about the remaining carrier was obtained from medical records. Clinical information about deceased individuals was obtained, when possible, from postmortem reports, death certificates and medical records.
RESULTS:
There have been eight sudden deaths; the cause of death was aortic dissection in all six cases in which a postmortem examination was performed. Three individuals had undergone aortic replacement surgery. Dissection had occurred throughout the aorta, and in one case in the absence of aortic root dilatation. Subarachnoid haemorrhage, due to a ruptured berry aneurysm, had occurred in two individuals. Four gene carriers and one deceased family member who were investigated had tortuous cerebral blood vessels. One had tortuous vertebral arteries, two had tortuous carotid arteries and one a tortuous abdominal aorta. Two individuals were found to have a brachiocephalic artery aneurysm and a subclavian artery aneurysm, respectively.
CONCLUSIONS:
Despite the predisposition to aortic dilatation and dissection, individuals did not frequently manifest the skeletal features of Marfan syndrome, with the exception of joint hypermobility. No one individual had ocular lens dislocation. Striae and herniae were common. There was some overlap with Ehlers-Danlos syndrome type 4, OMIM 130050, with soft translucent skin, which is easily bruised. Other features were arthralgia, migraine and a tendency to fatigue easily, varicose veins and prominent skin striae. This family provides further evidence that mutations in TGFbetaR2 cause a distinct syndrome that needs to be distinguished from Marfan syndrome to direct investigation and management of patients and shows the natural history, spectrum of clinical features and variable penetrance of this newly recognised condition.
0022-2593
908-916
Law, C
6a035610-9c96-46d4-a1b5-f010d47c9dc8
Bunyan, D.
53a89b0f-cfde-4f58-87f3-084c8e9c774e
Castle, B.
1472bdb8-2ec6-4b06-8d62-7a1e6190ca4d
Day, Lorna B.
e2afd522-a3f5-4b13-9da9-7f6f6306bc82
Simpson, I.
ceb12a1e-d254-43b6-9618-a0ee8087e701
Westwood, G.
371469db-5598-4c81-95b6-c17a3ed228f8
Keeton, B.
778e4304-5297-40ab-b785-5325e3321be1
Law, C
6a035610-9c96-46d4-a1b5-f010d47c9dc8
Bunyan, D.
53a89b0f-cfde-4f58-87f3-084c8e9c774e
Castle, B.
1472bdb8-2ec6-4b06-8d62-7a1e6190ca4d
Day, Lorna B.
e2afd522-a3f5-4b13-9da9-7f6f6306bc82
Simpson, I.
ceb12a1e-d254-43b6-9618-a0ee8087e701
Westwood, G.
371469db-5598-4c81-95b6-c17a3ed228f8
Keeton, B.
778e4304-5297-40ab-b785-5325e3321be1

Law, C, Bunyan, D., Castle, B., Day, Lorna B., Simpson, I., Westwood, G. and Keeton, B. (2006) Clinical features in a family with an R460H mutation in transforming growth factor receptor 2 gene. Journal of Medical Genetics, 43 (12), 908-916. (doi:10.1136/jmg.2006.042176). (PMID:16885183)

Record type: Article

Abstract

OBJECTIVES:
To describe the clinical findings and natural history in 22 carriers of an R460H mutation in the transforming growth factor beta receptor 2 gene (TGFbetaR2) from a five-generation kindred ascertained by familial aortic dissection.
METHODS:
13 of the confirmed carriers were interviewed and examined, and information about the remaining carrier was obtained from medical records. Clinical information about deceased individuals was obtained, when possible, from postmortem reports, death certificates and medical records.
RESULTS:
There have been eight sudden deaths; the cause of death was aortic dissection in all six cases in which a postmortem examination was performed. Three individuals had undergone aortic replacement surgery. Dissection had occurred throughout the aorta, and in one case in the absence of aortic root dilatation. Subarachnoid haemorrhage, due to a ruptured berry aneurysm, had occurred in two individuals. Four gene carriers and one deceased family member who were investigated had tortuous cerebral blood vessels. One had tortuous vertebral arteries, two had tortuous carotid arteries and one a tortuous abdominal aorta. Two individuals were found to have a brachiocephalic artery aneurysm and a subclavian artery aneurysm, respectively.
CONCLUSIONS:
Despite the predisposition to aortic dilatation and dissection, individuals did not frequently manifest the skeletal features of Marfan syndrome, with the exception of joint hypermobility. No one individual had ocular lens dislocation. Striae and herniae were common. There was some overlap with Ehlers-Danlos syndrome type 4, OMIM 130050, with soft translucent skin, which is easily bruised. Other features were arthralgia, migraine and a tendency to fatigue easily, varicose veins and prominent skin striae. This family provides further evidence that mutations in TGFbetaR2 cause a distinct syndrome that needs to be distinguished from Marfan syndrome to direct investigation and management of patients and shows the natural history, spectrum of clinical features and variable penetrance of this newly recognised condition.

Full text not available from this repository.

More information

e-pub ahead of print date: 2 August 2006
Published date: December 2006
Organisations: Faculty of Health Sciences

Identifiers

Local EPrints ID: 366285
URI: http://eprints.soton.ac.uk/id/eprint/366285
ISSN: 0022-2593
PURE UUID: 3086006f-af0b-4e90-91bd-297a59e03c2e

Catalogue record

Date deposited: 30 Jun 2014 12:12
Last modified: 16 Jul 2019 21:02

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×