Germline TGF-β receptor mutations and skeletal fragility: A report on two patients with Loeys-Dietz syndrome

Salman Kirmani, Peter Tebben, Aida N. Lteif, David Gordon, Bart Clarke, Theresa E. Hefferan, Michael J Yaszemski, Pamela S. McGrann, Noralane Morey Lindor, Jay W. Ellison

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Abstract

Loeys-Dietz syndrome (LDS, OMIM # 609192) caused by heterozygous mutations in TGFBR1 and TGFBR2 has recently been described as an important cause of familial aortic aneurysms. These patients have craniofacial and skeletal features that overlap with the Marfan syndrome (MFS), and more importantly, have significant vascular fragility as is seen in MFS and Ehlers-Danlos syndrome Type IV (EDS-IV). The skeletal phenotype with respect to low bone mineral density and skeletal fragility is not clear. We present two patients with LDS with significant skeletal fragility. The first is a 17-year-old male who had talipes equinovarus, diaphragmatic and inguinal and herniae, aortic root dilatation necessitating surgical repair, craniofacial and skeletal dysmorphism consistent with LDS, and a history of numerous fragility fractures leading to significant skeletal deformity. He was found to be heterozygous for a c.923T > C transition in exon 4 of TGFBR2. The second is a 26-year-old male with submucous cleft palate, talipes equinovarus, pectus excavatum requiring surgery, inguinal hernia, and aneurysms in the ascending aorta, abdominal aorta, carotid, subclavian, vertebral and brachial arteries requiring surgical repairs. He also had craniofacial and skeletal dysmorphism consistent with LDS, multiple fractures in childhood, low bone mineral density, and was found to be heterozygous for a c.1561 T > C transition in exon 7 of TGFBR2. These case studies highlight the importance of paying close attention to fractures and bone density in patients with LDS. Osteopenia or osteoporosis may become increasingly important issues as earlier detection and treatment of the vascular complications of LDS improves life expectancy in these patients.

Original languageEnglish (US)
Pages (from-to)1016-1019
Number of pages4
JournalAmerican Journal of Medical Genetics, Part A
Volume152
Issue number4
DOIs
StatePublished - Apr 2010

Fingerprint

Loeys-Dietz Syndrome
Bone Density
Clubfoot
Marfan Syndrome
Mutation
Inguinal Hernia
Blood Vessels
Exons
Funnel Chest
Ehlers-Danlos Syndrome
Genetic Databases
Subclavian Artery
Diaphragmatic Hernia
Brachial Artery
Vertebral Artery
Metabolic Bone Diseases
Abdominal Aorta
Cleft Palate
Life Expectancy
Carotid Arteries

Keywords

  • Aortic aneurysm
  • Bisphosphonates
  • Bone density
  • Bone histomorphometry
  • Fractures
  • Vascular fragility

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Germline TGF-β receptor mutations and skeletal fragility : A report on two patients with Loeys-Dietz syndrome. / Kirmani, Salman; Tebben, Peter; Lteif, Aida N.; Gordon, David; Clarke, Bart; Hefferan, Theresa E.; Yaszemski, Michael J; McGrann, Pamela S.; Lindor, Noralane Morey; Ellison, Jay W.

In: American Journal of Medical Genetics, Part A, Vol. 152, No. 4, 04.2010, p. 1016-1019.

Research output: Contribution to journalArticle

Kirmani, Salman ; Tebben, Peter ; Lteif, Aida N. ; Gordon, David ; Clarke, Bart ; Hefferan, Theresa E. ; Yaszemski, Michael J ; McGrann, Pamela S. ; Lindor, Noralane Morey ; Ellison, Jay W. / Germline TGF-β receptor mutations and skeletal fragility : A report on two patients with Loeys-Dietz syndrome. In: American Journal of Medical Genetics, Part A. 2010 ; Vol. 152, No. 4. pp. 1016-1019.
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AU - Hefferan, Theresa E.

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