Title
A study of the clinical and radiological features in a cohort of 93 patients with a COL2A1 mutation causing spondyloepiphyseal dysplasia congenita or a related phenotype
Author
Terhal, P.A.
Nievelstein, R.J.A.J.
Verver, E.J.J.
Topsakal, V.
van Dommelen, P.
Hoornaert, K.
le Merrer, M.
Zankl, A.
Simon, M.E.
Smithson, S.F.
Marcelis, C.
Kerr, B.
Clayton-Smith, J.
Kinning, E.
Mansour, S.
Elmslie, F.
Goodwin, L.
van der Hout, A.H.
Veenstra-Knol, H.E.
Herkert, J.C.
Lund, A.M.
Hennekam, R.C.
Mégarbané, A.
Lees, M.M.
Wilson, L.C.
Male, A.
Hurst, J.
Alanay, Y.
Annerén, G.
Betz, R.C.
Bongers, E.M.
Cormier-Daire, V.
Dieux, A.
David, A.
Elting, M.W.
van den Ende, J.
Green, A.
van Hagen, J.M.
Hertel, N.T.
Holder-Espinasse, M.
den Hollander, N.
Homfray, T.
Hove, H.D.
Price, S.
Raas-Rothschild, A.
Rohrbach, M.
Schroeter, B.
Suri, M.
Thompson, E.M.
Tobias, E.S.
Toutain, A.
Vreeburg, M.
Wakeling, E.
Knoers, N.V.
Coucke, P.
Mortier, G.R.
Publication year
2015
Abstract
Type 2 collagen disorders encompass a diverse group of skeletal dysplasias that are commonly associated with orthopedic, ocular, and hearing problems. However, the frequency of many clinical features has never been determined. We retrospectively investigated the clinical, radiological, and genotypic data in a group of 93 patients with molecularly confirmed SEDC or a related disorder. The majority of the patients (80/93) had short stature, with radiological features of SEDC (n = 64), others having SEMD (n = 5), Kniest dysplasia (n = 7), spondyloperipheral dysplasia (n = 2), or Torrance-like dysplasia (n = 2). The remaining 13 patients had normal stature with mild SED, Stickler-like syndrome or multiple epiphyseal dysplasia. Over 50% of the patients had undergone orthopedic surgery, usually for scoliosis, femoral osteotomy or hip replacement. Odontoid hypoplasia was present in 56% (95% CI 38-74) and a correlation between odontoid hypoplasia and short stature was observed. Atlanto-axial instability, was observed in 5 of the 18 patients (28%, 95% CI 10-54) in whom flexion-extension films of the cervical spine were available; however, it was rarely accompanied by myelopathy. Myopia was found in 45% (95% CI 35-56), and retinal detachment had occurred in 12% (95% CI 6-21; median age 14 years; youngest age 3.5 years). Thirty-two patients complained of hearing loss (37%, 95% CI 27-48) of whom 17 required hearing aids. The ophthalmological features and possibly also hearing loss are often relatively frequent and severe in patients with splicing mutations. Based on clinical findings, age at onset and genotype-phenotype correlations in this cohort, we propose guidelines for the management and follow-up in this group of disorders.
Subject
Behavioural Changes
LS - Life Style
ELSS - Earth, Life and Social Sciences
Healthy for Life
Health
Healthy Living
SEDC
Genotype-phenotype
Spondyloepiphyseal dysplasia
Review
SEDC
Aspartic acid
Glycine
Procollagen
Serine
Adolescent
Amino acid substitution
Atlantoaxial dislocation
Bronchomalacia
Child
Cleft palate
Clinical feature
Clubfoot
COL2A1 gene
Coxa vara
Disease severity
Female
Gene
Gene mutation
Genotype phenotype correlation
Gestational age
Hearing impairment
Heterozygosity
Hip arthroplasty
Hypermetropia
Major clinical study
Male
Missense mutation
Mutational analysis
Myopia
Osteotomy
Pierre Robin syndrome
Population research
Respiratory distress
Retina detachment
School child
Scoliosis
Spondyloepiphyseal dysplasia
Tracheomalacia
Tracheostomy
To reference this document use:
http://resolver.tudelft.nl/uuid:4f27859a-60be-4867-a4c9-ffb88eebcadb
DOI
https://doi.org/10.1002/ajmg.a.36922
TNO identifier
522295
Source
American Journal of Medical Genetics Part A, 167 (3), 1-15
Document type
article