Overview
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Achondroplasia, implying absent cartilage formation is a type of skeletal dysplasia which are a heterogeneous group of disorders characterized by intrinsic abnormalities in the growth or remodelling of cartilage and bone. They affect the skull, spine, and extremities in varying degrees.
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The characteristic feature of achondroplasia is a disproportionately short stature (dwarfism). The short stature mainly results from shortening of the limbs with proximal segments affected disproportionally, a phenotype referred as rhizomelia.
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Achondroplasia is the most common type of short-limb disproportionate dwarfism. More than 95% of patients have the same point mutation in the gene for fibroblast growth factor receptor 3 (FGFR3) which is inherited in an autosomal dominant pattern and more than 80% are new mutations.
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The Igenomix Achondroplasia Precision Panel can be used to make a directed and accurate differential diagnosis of disproportionately short stature ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved.
Indication
The Igenomix Achondroplasia Precision Panel is indicated for those patients with a suspected clinical diagnosis of achondroplasia presenting with the following manifestations:
- Disproportionate short stature
- Macrocephaly with frontal bossing
- Prominent mandible
- Shortening of the arms with redundant skin folds
- Limitation of elbow extension
- Delayed gross motor development
- Brachydactyly
- Exaggerated lumbar lordosis
- Thoracolumbar kyphosis
Clinical Utility
The clinical utility of this panel is:
- The genetic and molecular confirmation for an accurate clinical diagnosis of a symptomatic patient.
- Early initiation of treatment with a multidisciplinary team that includes supportive treatment in the form of medical care, early surgical care, rehabilitation and physical therapy.
- Prenatal detection of achondroplasia for a directed obstetric and perinatal treatment of affected infants.
- Risk assessment of asymptomatic family members according to the mode of inheritance.
Genes & Diseases
GENE |
OMIM DISEASES |
INHERITANCE* |
% GENE COVERAGE (20X) |
HGMD** |
FGFR3 |
Achondroplasia, Bladder Cancer, Camptodactyly-Tall Stature-Scoliosis-Hearing Loss Syndrome, Cervical Cancer, Colorectal Cancer, Crouzon Syndrome With Acanthosis Nigricans, Epidermal Nevus, Hypochondroplasia, Isolated brachycephaly, Isolated Plagiocephaly, Lacrimoauriculodentodigital Syndrome, Muenke Syndrome, Saethre-Chotzen Syndrome, Testicular Tumor, Thanatophoric Dysplasia Type 1, Type 2 |
AD,AR |
99.89% |
77 of 78 |
*Inheritance: AD: Autosomal Dominant; AR: Autosomal Recessive; X: X linked; XLR: X linked Recessive; Mi: Mitochondrial; Mu: Multifactorial.
**Number of clinically relevant mutations according to HGMD
References
Pauli, R. (2019). Achondroplasia: a comprehensive clinical review. Orphanet Journal Of Rare Diseases, 14(1). doi: 10.1186/s13023-018-0972-6
Horton, W., Hall, J., & Hecht, J. (2007). Achondroplasia. The Lancet, 370(9582), 162-172. doi: 10.1016/s0140-6736(07)61090-3
Baitner, A., Maurer, S., Gruen, M., & Di Cesare, P. (2000). The Genetic Basis of the Osteochondrodysplasias. Journal Of Pediatric Orthopaedics, 594-605. doi: 10.1097/00004694-200009000-00010
Ornitz, D. M., & Legeai-Mallet, L. (2017). Achondroplasia: Development, pathogenesis, and therapy. Developmental dynamics : an official publication of the American Association of Anatomists, 246(4), 291–309. https://doi.org/10.1002/dvdy.24479
Daugherty A. (2017). Achondroplasia: Etiology, Clinical Presentation, and Management. Neonatal network : NN, 36(6), 337–342. https://doi.org/10.1891/0730-0832.36.6.337
Horton, W., Hall, J., & Hecht, J. (2007). Achondroplasia. The Lancet, 370(9582), 162-172. doi: 10.1016/s0140-6736(07)61090-3
Legare JM. Achondroplasia. 1998 Oct 12 [Updated 2020 Aug 6]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1152/