Severe Thoracic and Spinal Bone Abnormalities in neurofibromatosis type 1

Area of Science:

• Genetics
• Orthopedics
• Pulmonology

Background:

• Neurofibromatosis type 1 (NF1) is a genetic disorder causing tumors and skeletal issues.
• Scoliosis affects approximately 10% of NF1 patients, ranging from non-dystrophic to severe dystrophic forms.

Observation:

• A 17-year-old male with NF1 presented with severe spinal and thoracic malformations.
• These included hypoplastic right lung, unilateral costal agenesis, and complex dystrophic scoliosis (hemivertebrae, vertebral fusion, defective pedicles).
• The patient experienced respiratory distress at birth, requiring ventilation.

Findings:

• NF1 diagnosis confirmed by a de novo mutation (c.4537C>T, p.Arg1513*) in the NF1 gene.
• Whole Exome Sequencing excluded other significant pathogenic variants.
• This presentation is exceptionally rare, with only one similar case previously reported.

Implications:

• Severe NF1-related scoliosis may impede fetal lung development due to mechanical constraints.
• Extreme thoracic and spinal bone abnormalities should be recognized as part of the NF1 phenotype.
• Awareness of these severe manifestations is crucial for accurate genetic counseling in NF1.