Hand and fibrillin-1 deposition abnormalities in Loeys-Dietz syndrome--expanding the clinical spectrum.

Abstract

Loeys-Dietz syndrome (LDS) is an autosomal dominant connective tissue disorder characterized by hypertelorism, bifid uvula, cleft palate and arterial tortuosity. We report on a patient with LDS, bearing mutation in the TGFβR2 gene, whose prenatal examination demonstrated clenched fists and club feet, suggesting arthrogryposis multiplex congenita. Postnatal assessment showed digital abnormalities, including brachydactyly, camptodactyly, partial syndactyly and absent distal phalanges. With the lack of fibrillin-1 microfibril deposition as well as impaired and inadequate elastic fiber assembly in our patient's fibroblasts, we speculate that the skeletal abnormalities seen in this patient with LDS are the result of lack of these components in embryonal perichondrium and in blood vessels. We suggest that LDS should be included in the differential diagnosis of joint contractures seen pre and postnatally. Prenatal diagnosis of LDS would be important in parental counseling and early post natal diagnosis could prompt treatment before the development of detrimental vascular complications.

• Authors: Brian H Y Chung, Tim Bradley, Lars Grosse-Wortmann, Susan Blaser, Peter Dirks, Aleksander Hinek, David Chitayat
• Journal: American journal of medical genetics. Part A (Am J Med Genet A) Vol. 164A Issue 2 Pg. 461-6 (Feb 2014) ISSN: 1552-4833 [Electronic] United States
• PMID: 24194458 (Publication Type: Case Reports, Journal Article)
• Copyright: © 2013 Wiley Periodicals, Inc.

Chemical References

• FBN1 protein, human
• Fibrillin-1
• Fibrillins
• Microfilament Proteins
• Receptors, Transforming Growth Factor beta
• Protein Serine-Threonine Kinases
• Receptor, Transforming Growth Factor-beta Type II

Topics

• Abnormalities, Multiple
• Cells, Cultured
• DNA Mutational Analysis
• Dermis (cytology, metabolism)
• Fibrillin-1
• Fibrillins
• Fibroblasts (metabolism)
• Hand Deformities, Congenital
• Humans
• Infant, Newborn
• Loeys-Dietz Syndrome (diagnosis, genetics, metabolism)
• Male
• Microfilament Proteins (metabolism)
• Phenotype
• Prenatal Diagnosis
• Protein Serine-Threonine Kinases (genetics)
• Receptor, Transforming Growth Factor-beta Type II
• Receptors, Transforming Growth Factor beta (genetics)