Severe Thoracic and Spinal Bone Abnormalities in neurofibromatosis type 1

Eur J Med Genet. 2020 Apr;63(4):103815. doi: 10.1016/j.ejmg.2019.103815. Epub 2019 Nov 26.


Neurofibromatosis type 1 (NF1) is an autosomal dominant, multi-system, neurocutaneous disorder that predisposes to the development of benign and malignant tumors. Classical skeletal abnormalities encompass sphenoid wing dysplasia, congenital bowing of the long bones and vertebral osteopathy associated with non-dystrophic or dystrophic scoliosis found in about 10% of NF1 patients. We report a 17-year-old boy affected by NF1 with extreme severe spinal and thoracic malformations affecting bone and lung tissues, including hypoplasia of the right lung, unilateral costal agenesis and severe dystrophic scoliosis characterized by association of hemivertebra, fusion of adjacent vertebral bodies and defective pedicles. At birth, he presented an acute respiratory distress requiring invasive ventilator support. The diagnosis of NF1 was confirmed at age 5 by the identification of a de novo heterozygous mutation c.4537C > T, p.Arg1513* in NF1. Trio-based Whole Exome Sequencing (WES) was performed to exclude coexistence of a second hit but no clearly other pathogenic variant has been identified. Until now, only one similar NF1 patient suffering from the same association of severe scoliosis and chest deformity leading to respiratory insufficiency was described. The severe prenatal NF1-related scoliosis could explain the lung abnormal development by absence of mechanical constraints. Severe Thoracic and Spinal Bone Abnormalities may be part of the NF1 bone phenotype and should be taken into account to allow adequate genetic counseling.

Keywords: Bone abnormalities; NF1; Neurofibromatosis type 1; Respiratory insufficiency; Scoliosis.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Exome Sequencing
  • Humans
  • Male
  • Neurofibromatosis 1 / diagnostic imaging
  • Neurofibromatosis 1 / genetics*
  • Neurofibromin 1 / genetics*
  • Spine / abnormalities*
  • Spine / diagnostic imaging
  • Thorax / abnormalities*
  • Thorax / diagnostic imaging
  • Tomography, X-Ray Computed


  • NF1 protein, human
  • Neurofibromin 1