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Atlas of Genetic Diagnosis and Counseling pp 21–34Cite as

Achondroplasia

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Achondroplasia is the most common form of short-limbed dwarfism. Gene frequency is estimated to be 1/16,000 and 1/35,000. There are about 5,000 achondroplasts in the U.S.A. and 65,000 on Earth. The incidence for achondroplasia is between 0.5 and 1.5 in 10,000 births. The mutation rate is high and is estimated to be between 1.72 and 5.57 × 10−5 per gamete per generation. Most infants with achondroplasia are born unexpectedly to parents of average stature.

Genetics/Basic Defects

  1. 1.

    Inheritance

    1. a.

      Autosomal dominant disorder with complete penetrance

    2. b.

      Sporadic in about 80% of the cases, the result of a de novo mutation

    3. c.

      Presence of paternal age effect (advanced paternal age in sporadic cases)

    4. d.

      Gonadal mosaicism (two or more children with classic achondroplasia born to normal parents)

  2. 2.

    Caused by mutations in the gene of the fibroblast growth factor receptor 3 (FGFR3) on chromosome 4p16.3

    1. a.

      About 98% of achondroplasia with G-to-A transition and about 1% G-to-C transversion at...

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References

  • Aldegheri, R., Trivella, G., Renzi-Brivio, L., et al. (1988). Lengthening of the lower limbs in achondroplastic patients. A comparative study of four techniques. The Journal of Bone and Joint Surgery, 70B, 69–73.

    Google Scholar 

  • Allanson, J. E., & Hall, J. G. (1986). Obstetrics and gynecologic problems in women with chondrodystrophies. Obstetrics and Gynecology, 67, 74–78.

    PubMed  CAS  Google Scholar 

  • American Academy of Pediatrics Committee on Genetics. (1995). Health supervision for children with achondroplasia. Pediatrics, 95, 443–451.

    Google Scholar 

  • American Academy of Pediatrics: Clinical Report. (2005). Health supervision for children with achondroplasia. Pediatrics, 116, 771–783.

    Article  Google Scholar 

  • Baujat, G., Legeai-Mallet, L., Finidori, G., et al. (2008). Achondroplasia. Best Practice & Research. Clinical Rheumatology, 22, 3–18.

    Article  CAS  Google Scholar 

  • Bellus, G. A., Hefferon, T. W., Ortiz de Luna, R. I., et al. (1995). Achondroplasia is defined by recurrent G380R mutations of FGFR3. American Journal of Human Genetics, 56, 368–373.

    PubMed  CAS  Google Scholar 

  • Boulet, S., Althuser, M., Nugues, F., et al. (2009). Prenatal diagnosis of achondroplasia: New specific signs. Prenatal Diagnosis, 29, 697–702.

    Article  PubMed  Google Scholar 

  • Carter, E. M., Davis, J. G., & Raggio, C. L. (2007). Advances in understanding etiology of achondroplasia and review of management. Current Opinion in Pediatrics, 19, 32–37.

    Article  PubMed  Google Scholar 

  • Chen, H., Mu, X., Sonoda, T., et al. (2000). FGFR3 gene mutation (Gly380Arg) with achondroplasia and i(21q) Down syndrome: Phenotype-genotype correlation. Southern Medical Journal, 93, 622–624.

    PubMed  CAS  Google Scholar 

  • Cordone, M., Lituania, M., Bocchino, G., et al. (1993). Ultrasonographic features in a case of heterozygous achondroplasia at 25 weeks’ gestation. Prenatal Diagnosis, 13, 395–401.

    Article  PubMed  CAS  Google Scholar 

  • Francomano, C. A. (2006). Achondroplasia. GeneReviews. Retrieved January 9, 2006. Available at: http://www.ncbi.nlm.nih.gov/books/NBK1152/

  • Fryns, J. P., Kleczkowska, A., Verresen, H., et al. (1983). Germinal mosaicism in achondroplasia: A family with 3 affected siblings of normal parents. Clinical Genetics, 24, 156–158.

    Article  PubMed  CAS  Google Scholar 

  • Ganel, A., & Horoszowski, H. (1996). Limb lengthening in children with achondroplasia. Differences based on gender. Clinical Orthopaedics and Related Research, 332, 179–183.

    Article  PubMed  Google Scholar 

  • Ganel, A., Horoszowski, H., Kamhin, M., et al. (1979). Leg lengthening in achondroplastic children. Clinical Orthopaedics, 144, 194–197.

    Google Scholar 

  • Hall, J. G., Dorst, J., Taybi, H., et al. (1969). Two probable cases of homozygosity for the achondroplasia gene. Birth Defects Original Article Series, V(4), 24–34.

    Google Scholar 

  • Hall, J. G., et al. (1988). The natural history of achondroplasia. In B. Nicoletti, S. E. Kopits, & E. Ascani (Eds.), Human achondroplasia: A multidisciplinary approach (pp. 3–10). New York: Plenum Press.

    Google Scholar 

  • Hecht, J. T., & Butler, I. J. (1990). Neurologic morbidity associated with achondroplasia. Journal of Child Neurology, 5, 84–97.

    Article  PubMed  CAS  Google Scholar 

  • Hecht, J. T., Francomano, C. A., Horton, W. A., et al. (1987). Mortality in achondroplasia. American Journal of Human Genetics, 41, 454–464.

    PubMed  CAS  Google Scholar 

  • Henderson, S., Sillence, D., Loughlin, J., et al. (2000). Germline and somatic mosaicism in achondroplasia. Journal of Medical Genetics, 37, 956–958.

    Article  PubMed  CAS  Google Scholar 

  • Hoover-Fong, J. E., McGready, J., Schulze, K. J., et al. (2007). Weight for age charts for children with achondroplasia. American Journal of Medical Genetics. Part A, 143A, 2227–2235.

    Article  PubMed  CAS  Google Scholar 

  • Horton, W. A. (1996). Molecular genetic basis of the human chondrodysplasias. Endocrinology and Metabolism Clinics of North America, 25, 683–697.

    Article  PubMed  CAS  Google Scholar 

  • Horton, W. A. (1997). Fibroblast growth factor receptor 3 and the human chondrodysplasias. Current Opinion in Pediatrics, 9, 437–442.

    Article  PubMed  CAS  Google Scholar 

  • Horton, W. A., Hall, J. G., & Hecht, J. T. (2007). Achondroplasia. Lancet, 370, 162–172.

    Article  PubMed  CAS  Google Scholar 

  • Horton, W. A., Hecht, J. T., Hood, O. J., et al. (1992). Growth hormone therapy in achondroplasia. American Journal of Medical Genetics, 42, 667–670.

    Article  PubMed  CAS  Google Scholar 

  • Horton, W. A., Hood, O. J., Machado, M. A., et al. (1988). Growth plate cartilage studies in achondroplasia. In B. Nicoletti, S. E. Kopits, E. Ascani, et al. (Eds.), Human achondroplasia: A multidisciplinary approach (pp. 81–89). New York: Plenum Press.

    Google Scholar 

  • Horton, W. A., Rotter, J. I., Rimoin, D. L., et al. (1978). Standard growth curves for achondroplasia. Journal of Pediatrics, 93, 435–438.

    Article  PubMed  CAS  Google Scholar 

  • Hunter, A. G. W., Bankier, A., Rogers, J. G., et al. (1998). Medical complications of achondroplasia: A multicenter patient review. Journal of Medical Genetics, 35, 705–712.

    Article  PubMed  CAS  Google Scholar 

  • Hunter, A. G. W., Hecht, J. T., & Scott, C. I. (1996). Standard weight for height curves in achondroplasia. American Journal of Medical Genetics, 62, 255–261.

    Article  PubMed  CAS  Google Scholar 

  • King, J. A. J., Vachhrajani, S., Drake, J. M., et al. (2009). Neurosurgical implications of achondroplasia. A review. Journal of Neurosurgery. Pediatrics, 4, 297–306.

    Article  PubMed  Google Scholar 

  • Kornblum, M., & Stanitski, D. F. (1999). Spinal manifestations of skeletal dysplasias. Orthopedic Clinics of North America, 30, 501–520.

    Article  PubMed  CAS  Google Scholar 

  • Krakow, D., Williams, J., 3rd, Poehl, M., et al. (2003). Use of three-dimensional ultrasound imaging in the diagnosis of prenatal-onset skeletal dysplasias. Ultrasound in Obstetrics & Gynecology, 21, 467–472.

    Article  CAS  Google Scholar 

  • Langer, L. O., Jr., Baumann, P. A., & Gorlin, R. J. (1967). Achondroplasia. American Journal of Roentgenology, 100, 12–26.

    Google Scholar 

  • Lattanzi, D. R., & Harger, J. H. (1982). Achondroplasia and pregnancy. The Journal of Reproductive Medicine, 27, 363–366.

    PubMed  CAS  Google Scholar 

  • Lavini, F., Renzi-Brivio, L., & de Bastiani, G. (1990). Psychologic, vascular, and physiologic aspects of lower limb lengthening in achondroplastics. Clinical Orthopaedics and Related Research, 250, 138–142.

    PubMed  Google Scholar 

  • Lemyre, E., Azouz, E. M., Teebi, A. S., et al. (1999). Bone dysplasia series. Achondroplasia, hypochondroplasia and thanatophoric dysplasia: Review and update. Canadian Association of Radiologists Journal, 50, 185–197.

    PubMed  CAS  Google Scholar 

  • Lutter, L. D., & Langer, L. O. (1977). Neurologic symptoms in achondroplastic dwarfs-surgical treatment. The Journal of Bone and Joint Surgery, 59(1), 87–92.

    PubMed  CAS  Google Scholar 

  • Mesoraca, A., Pilu, G., Perolo, A., et al. (1996). Ultrasound and molecular mid-trimester prenatal diagnosis of de novo achondroplasia. Prenatal Diagnosis, 16, 764–768.

    Article  PubMed  CAS  Google Scholar 

  • Mettler, G., & Fraser, F. C. (2000). Recurrence risk for sibs of children with “sporadic” achondroplasia. American Journal of Medical Genetics, 90, 250–251.

    Article  PubMed  CAS  Google Scholar 

  • Mogayzel, P. J., Jr., Carroll, J. L., Loughlin, G. M., et al. (1998). Sleep-disordered breathing in children with achondroplasia. Journal of Pediatrics, 132, 667–671.

    Article  PubMed  Google Scholar 

  • Moutou, C., Rongieres, C., Bettahar-Lebugle, K., et al. (2003). Preimplantation genetic diagnosis for achondroplasia: Genetics and gynaecological limits and difficulties. Human Reproduction, 18, 509–514.

    Article  PubMed  CAS  Google Scholar 

  • Natacci, F., Baffico, M., Cavallari, U., et al. (2008). Germline mosaicism in achondroplasia detected in sperm DNA of the father of three affected sibs. American Journal of Medical Genetics. Part A, 146A, 784–786.

    Article  PubMed  CAS  Google Scholar 

  • Overlaid, F., Danks, D. M., Jensen, F., et al. (1979). Achondroplasia and hypochondroplasia. Comments on frequency, mutation rate, and radiological features in skull and spine. Journal of Medical Genetics, 16, 140–146.

    Article  Google Scholar 

  • Patel, M. D., & Filly, R. A. (1995). Homozygous achondroplasia: US distinction between homozygous, heterozygous, and unaffected fetuses in the second trimester. Radiology, 196, 541–545.

    PubMed  CAS  Google Scholar 

  • Pauli, R. M. (2001). Achondroplasia. In S. B. Cassidy & J. E. Allanson (Eds.), Management of genetic syndromes. New York: Wiley-Liss.

    Google Scholar 

  • Philip, N., Auger, M., Mattei, J. F., et al. (1988). Achondroplasia in sibs of normal parents. Journal of Medical Genetics, 25, 857–859.

    Article  PubMed  CAS  Google Scholar 

  • Pierre-Kahn, A., Hirsch, J. F., Renier, D., et al. (1980). Hydrocephalus and achondroplasia. A study of 25 observations. Child's Brain, 7, 205–219.

    PubMed  CAS  Google Scholar 

  • Prinos, P., Kilpatrick, M. W., Tsipouras, P., et al. (1994). A novel G346E mutation in achondroplasia. Pediatric Research, 37, 151.

    Google Scholar 

  • Richette, P., Bardin, T., & Stheneur, C. (2008). Achondroplasia: From genotype to phenotype. Joint, Bone, Spine, 75, 125–130.

    Article  PubMed  Google Scholar 

  • Rimoin, D. L. (1991). Limb lengthening: Past, present, and future. Growth Genetics and Hormones, 7, 4–6.

    Google Scholar 

  • Rousseau, F., Bonaventure, J., Legeal-Mallet, L., et al. (1994). Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia. Nature, 371, 252–254.

    Article  PubMed  CAS  Google Scholar 

  • Ruano, R., Molho, M., Roume, J., et al. (2004). Prenatal diagnosis of fetal skeletal dysplasias by combining two dimensional and three-dimensional ultrasound and intrauterine three-dimensional helical computer tomography. Ultrasound in Obstetrics & Gynecology, 24, 134–140.

    Article  CAS  Google Scholar 

  • Seino, Y., Yamanaka, Y., Shinohanora, M., et al. (2000). Growth hormone therapy in achondroplasia. Hormone Research, 533, 53–56.

    Article  Google Scholar 

  • Shiang, R., Thompson, L. M., Zhu, Y.-Z., et al. (1994). Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell, 78, 335–342.

    Article  PubMed  CAS  Google Scholar 

  • Shirley, E. D., & Ain, M. C. (2009). Achondroplasia: Manifestations and treatment. Journal of the American Academy of Orthopaedic Surgeons, 17, 231–241.

    PubMed  Google Scholar 

  • Shohat, M., Tick, D., Barakat, S., et al. (1996). Short-term recombinant human growth hormone treatment increases growth rate in achondroplasia. The Journal of Clinical Endocrinology and Metabolism, 81, 4033–4037.

    Article  PubMed  CAS  Google Scholar 

  • Spranger, J. W., Langer, L. O., Jr., & Wiedemann, H. R. (1974). Bone dysplasias. An atlas of constitutional disorders of skeletal development. Philadelphia: WB Saunders.

    Google Scholar 

  • Stratbucker, W. B., & Serwint, J. R. (2009). In brief: Achondroplasia. Pediatrics in Review, 30, 114–115.

    Article  PubMed  Google Scholar 

  • Superti-Furga, A., & Unger, S. (2007). Nosology and classification of genetic skeletal disorders: 2006 revision. American Journal of Medical Genetics. Part A, 143A, 1–18.

    Article  Google Scholar 

  • Todorov, A. B., Scott, C. I., Warren, A. E., et al. (1981). Developmental screening tests in achondroplastic children. American Journal of Medical Genetics, 9, 19–23.

    Article  PubMed  CAS  Google Scholar 

  • Vajo, Z., Francomano, C. A., & Wilkin, D. J. (2000). The molecular and genetic basis of fibroblast growth factor receptor 3 disorders: The achondroplasia family of skeletal dysplasias, Muenke craniosynostosis, and Crouzon syndrome with acanthosis nigricans. Endocrine Reviews, 21, 23–39.

    Article  PubMed  CAS  Google Scholar 

  • Velinov, M., Slaugenhaupt, S. A., Stoilov, I., et al. (1994). The gene for achondroplasia maps to the telomeric region of chromosome 4p. Nature Genetics, 6, 318–321.

    Article  Google Scholar 

  • Wynn, J., King, T. M., Gambello, M. J., et al. (2007). Mortality in achondroplasia study: A 42-year follow-up. American Journal of Medical Genetics. Part A, 143A, 2502–2511.

    Article  PubMed  Google Scholar 

  • Yang, S. S., Corbett, D. P., Brough, A. J., et al. (1977). Upper cervical myelopathy in achondroplasia. American Journal of Clinical Pathology, 68, 68–72.

    PubMed  CAS  Google Scholar 

  • Yang, S. S., & Gilbert-Barnes, E. (1997). Skeletal system. In E. Gilbert-Barness (Ed.), Potter’s pathology of the fetus and infant (pp. 1423–1478). St Louis: Mosby.

    Google Scholar 

  • Yasui, N., Kawahata, H., Kojimoto, H., et al. (1997). Lengthening of the lower limbs in patients with achondroplasia and hypochondroplasia. Clinical Orthopaedics, 344, 298–306.

    Article  Google Scholar 

  • Zucconi, M., Weber, G., Castronova, V., et al. (1996). Sleep and upper airway obstruction in children with achondroplasia. Journal of Pediatrics, 129, 743–749.

    Article  PubMed  CAS  Google Scholar 

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Editor information

Editors and Affiliations

  1. Perinatal and Clinical Genetics, Department of Pediatrics, LSU Health Sciences Center, 1501 Kings Highway, Shreveport, LA, 71130, USA

    Harold Chen

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(2012). Achondroplasia. In: Chen, H. (eds) Atlas of Genetic Diagnosis and Counseling. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-1037-9_3

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