Severe Thoracic and Spinal Bone Abnormalities in neurofibromatosis type 1.
European Journal of Medical Genetics. 2020-04-01; 63(4): 103815
DOI: 10.1016/j.ejmg.2019.103815
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1. Eur J Med Genet. 2020 Apr;63(4):103815. doi: 10.1016/j.ejmg.2019.103815. Epub
2019 Nov 26.
Severe Thoracic and Spinal Bone Abnormalities in neurofibromatosis type 1.
Prudhomme L(1), Delleci C(2), Trimouille A(1), Chateil JF(3), Prodhomme O(4),
Goizet C(5), Van Gils J(6).
Author information:
(1)Service de Génétique Médicale, CHU Bordeaux, et laboratoire MRGM, INSERM
U1211, Univ. Bordeaux, Bordeaux, France.
(2)Centre de Référence Maladies Rares Neurogénétique, Service de Génétique
Médicale, CHU, Bordeaux, France; Service de Médecine Physique et de Réadaptation
Pôle de Neurosciences Cliniques, CHU de Bordeaux & EA 4136 HACS (handicap
Activité Cognition Santé), Université de Bordeaux, France.
(3)Service d’imagerie antenatale, de l’enfant et de la femme Univ. Bordeaux, RMSB
UMR 5536, France.
(4)Service d’Imagerie Pédiatrique CHU Hôpital Arnaud de Villeneuve, Montpellier,
France.
(5)Service de Génétique Médicale, CHU Bordeaux, et laboratoire MRGM, INSERM
U1211, Univ. Bordeaux, Bordeaux, France; Centre de Référence Maladies Rares
Neurogénétique, Service de Génétique Médicale, CHU, Bordeaux, France.
(6)Service de Génétique Médicale, CHU Bordeaux, et laboratoire MRGM, INSERM
U1211, Univ. Bordeaux, Bordeaux, France. Electronic address:
.
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.
Copyright © 2019 Elsevier Masson SAS. All rights reserved.
DOI: 10.1016/j.ejmg.2019.103815
PMID: 31783133 [Indexed for MEDLINE]