A novel mutation in the COL2A1 gene in a patient with Stickler syndrome type 1: a case report and review of the literature

J Med Case Rep. 2017 Aug 26;11(1):237. doi: 10.1186/s13256-017-1396-y.


Background: Stickler syndrome is a group of collagenopathies characterized by ophthalmic, skeletal, and orofacial abnormalities, with the degree of symptoms varying among patients. Mutations in the COL2A1, COL11A1, and COL11A2 procollagen genes cause Stickler syndrome. Marshall syndrome, caused by a COL11A1 mutation, has clinical overlap with Stickler syndrome.

Case presentation: A 2-year-old Japanese boy was presented to our hospital with short stature (79.1 cm, -2.52 standard deviation). His past medical history was significant for soft cleft palate and bilateral cataracts. He had a flat midface, micrognathia, and limitations in bilateral elbow flexion. Radiographs showed mild spondyloepiphyseal dysplasia. Initially, we suspected Marshall syndrome, but no mutation was identified in COL11A1. At 8 years old, his height was 116.2 cm (-1.89 standard deviation), and his orofacial characteristics appeared unremarkable. We analyzed the COL2A1 gene and found a novel heterozygous mutation (c.1142 G > A, p.Gly381Asp).

Conclusions: In this case report, we identify a novel missense mutation in the COL2A1 gene in a patient with Stickler syndrome type 1, and we describe age-related changes in the clinical phenotype with regard to orofacial characteristics and height. Genetic analysis is helpful for the diagnosis of this clinically variable and genetically heterogeneous disorder.

Keywords: COL2A1; Marshall syndrome; Stickler syndrome; Type II collagenopathy.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Arthritis / complications
  • Arthritis / diagnosis
  • Arthritis / genetics*
  • Cataract / diagnosis
  • Cataract / etiology
  • Cataract / genetics
  • Child
  • Child, Preschool
  • Cleft Palate / etiology
  • Cleft Palate / genetics
  • Collagen Type II / genetics*
  • Collagen Type XI / deficiency
  • Connective Tissue Diseases / complications
  • Connective Tissue Diseases / diagnosis
  • Connective Tissue Diseases / genetics*
  • Craniofacial Abnormalities / diagnosis
  • Diagnosis, Differential
  • Growth Disorders / etiology
  • Growth Disorders / genetics
  • Hearing Loss, Sensorineural / complications
  • Hearing Loss, Sensorineural / diagnosis
  • Hearing Loss, Sensorineural / genetics*
  • Humans
  • Male
  • Micrognathism / etiology
  • Micrognathism / genetics
  • Mutation
  • Osteochondrodysplasias / diagnosis
  • Osteochondrodysplasias / etiology
  • Osteochondrodysplasias / genetics
  • Palate, Soft / abnormalities
  • Phenotype
  • Retinal Detachment / complications
  • Retinal Detachment / diagnosis
  • Retinal Detachment / genetics*


  • COL2A1 protein, human
  • Collagen Type II
  • Collagen Type XI

Supplementary concepts

  • Cleft Soft Palate
  • Marshall syndrome
  • Stickler syndrome, type 1