TY - JOUR
T1 - Hand and fibrillin-1 deposition abnormalities in Loeys-Dietz syndrome-expanding the clinical spectrum
AU - Chung, Brian H.Y.
AU - Bradley, Tim
AU - Grosse-Wortmann, Lars
AU - Blaser, Susan
AU - Dirks, Peter
AU - Hinek, Aleksander
AU - Chitayat, David
N1 - Copyright:
Copyright 2014 Elsevier B.V., All rights reserved.
PY - 2014/2
Y1 - 2014/2
N2 - 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.
AB - 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.
KW - Arthrogryposis multiplex congenita
KW - Club feet
KW - Hand malformations
KW - Loeys-Dietz syndrome
KW - Skeletal abnormalities
UR - http://www.scopus.com/inward/record.url?scp=84892851078&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84892851078&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.36246
DO - 10.1002/ajmg.a.36246
M3 - Article
C2 - 24194458
AN - SCOPUS:84892851078
SN - 1552-4825
VL - 164
SP - 461
EP - 466
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 2
ER -