Severe hypotonia and postnatal growth impairment in a girl with a missense mutation in COL1A1: Implication of expanded phenotypic spectrum of type I collagenopathy

Brain Dev. 2017 Oct;39(9):799-803. doi: 10.1016/j.braindev.2017.04.020. Epub 2017 Jun 28.

Abstract

Background: It is known that type I collagenopathy has a broad-spectrum phenotypic variability. Here, we report a case of a Korean girl with a heterozygous COL1A1 mutation who had an atypical presentation.

Case presentation: A 26-month-old girl presented with delayed motor development and failure to thrive. She had severe growth retardation. She exhibited right-sided plagiocephaly, blue sclerae, and facial dysmorphism, including a small pointed chin, frontal bossing, and a triangular face, but had microcephaly. Whole-exome sequencing revealed a novel de novo heterozygous sequence variant in COL1A1 (p.Gly1127Asp), which was validated by Sanger sequencing. Radiological finding showed generalized osteoporosis with progressive scoliosis of the spine without evidence of platyspondyly related to fractures and bowing of the long bones, and markedly delayed carpal bone age. Muscle pathology showed a marked size variation of myofibers and selective type 1 atrophy.

Conclusions: This study expanded the clinical and genetic spectrum of type I collagenopathy with a COL1A1 variant. Therefore, we suggest that type I collagenopathy should be considered in the patients who have some features of osteogenesis imperfecta simultaneously with atypical features such as facial dysmorphism.

Keywords: COL1A1; Dysmorphism; Osteogenesis imperfecta; Type I collagenopathy; Whole-exome sequencing.

Publication types

  • Case Reports

MeSH terms

  • Child, Preschool
  • Collagen Type I / genetics*
  • Collagen Type I, alpha 1 Chain
  • DNA Mutational Analysis
  • Developmental Disabilities / complications
  • Developmental Disabilities / diagnostic imaging
  • Developmental Disabilities / genetics*
  • Female
  • Humans
  • Muscle Hypotonia / complications
  • Muscle Hypotonia / diagnostic imaging
  • Muscle Hypotonia / genetics*
  • Mutation, Missense / genetics*
  • Tomography Scanners, X-Ray Computed

Substances

  • Collagen Type I
  • Collagen Type I, alpha 1 Chain