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.
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.
authors.affiliation: Department of Medical Genetics, University Medical Centre Utrecht, Utrecht, The Netherlands.
authors.forename: Paulien A
authors.initials: PA
authors.lastname: Terhal
authors.forename: Rutger Jan A J
authors.initials: RJ
authors.lastname: Nievelstein
authors.forename: Eva J J
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authors.lastname: Verver
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authors.lastname: Cormier-Daire
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authors.lastname: Dieux
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authors.forename: Mariet W
authors.initials: MW
authors.lastname: Elting
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authors.lastname: van den Ende
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authors.lastname: Green
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authors.lastname: van Hagen
authors.forename: Niels Thomas
authors.initials: NT
authors.lastname: Hertel
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authors.lastname: Holder-Espinasse
authors.forename: Nicolette
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authors.lastname: den Hollander
authors.forename: Tessa
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authors.lastname: Homfray
authors.forename: Hanne D
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authors.lastname: Hove
authors.forename: Susan
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authors.lastname: Price
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authors.lastname: Raas-Rothschild
authors.forename: Marianne
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authors.lastname: Rohrbach
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authors.lastname: Schroeter
authors.forename: Mohnish
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authors.lastname: Suri
authors.forename: Elizabeth M
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authors.lastname: Thompson
authors.forename: Edward S
authors.initials: ES
authors.lastname: Tobias
authors.forename: Annick
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authors.lastname: Toutain
authors.forename: Maaike
authors.initials: M
authors.lastname: Vreeburg
authors.forename: Emma
authors.initials: E
authors.lastname: Wakeling
authors.forename: Nine V
authors.initials: NV
authors.lastname: Knoers
authors.forename: Paul
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authors.lastname: Coucke
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authors.lastname: Mortier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D024043:Collagen Type II / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010009:Osteochondrodysplasias / Q000151:congenital* / Q000000981:diagnostic imaging / Q000235:genetics; D010641:Phenotype; D011859:Radiography; D055815:Young Adult
chemical_list: C499177:COL2A1 protein, human; D024043:Collagen Type II
keywords: COL2A1; SEDC; genotype-phenotype; review; spondyloepiphyseal dysplasia