Genetics of Achondroplasia Differential Diagnoses

  • Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Bruce Buehler, MD   more...
 
Updated: Apr 16, 2012
 
 

Differential Diagnoses

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Contributor Information and Disclosures
Author

Germaine L Defendi, MD, MS, FAAP  Associate Clinical Professor, Department of Pediatrics, Olive View-UCLA Medical Center

Germaine L Defendi, MD, MS, FAAP is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Specialty Editor Board

James Bowman, MD  Senior Scholar of Maclean Center for Clinical Medical Ethics, Professor Emeritus, Department of Pathology, University of Chicago

James Bowman, MD is a member of the following medical societies: Alpha Omega Alpha, American Society for Clinical Pathology, American Society of Human Genetics, Central Society for Clinical Research, and College of American Pathologists

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Hagop Youssoufian, MD, MSc  Vice President of Clinical Research, ImClone Systems Incorporated

Hagop Youssoufian, MD, MSc is a member of the following medical societies: American Society for Clinical Investigation, American Society of Clinical Oncology, American Society of Hematology, and American Society of Human Genetics

Disclosure: Nothing to disclose.

Paul D Petry, DO, FACOP, FAAP  Consulting Staff, Freeman Pediatric Care, Freeman Health System

Paul D Petry, DO, FACOP, FAAP is a member of the following medical societies: American Academy of Osteopathy, American Academy of Pediatrics, American College of Osteopathic Pediatricians, and American Osteopathic Association

Disclosure: Nothing to disclose.

Chief Editor

Bruce Buehler, MD  Professor, Department of Pediatrics and Genetics, Director RSA, University of Nebraska Medical Center

Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association

Disclosure: Nothing to disclose.

Additional Contributors

The authors and editors of eMedicine gratefully acknowledge the contributions of previous authors Joo-Hee Grace Park, DO and Robert Wallerstein, MD, to the original writing and development of this article.

References

  1. Schlüter B, De Sousa G, Trowitzsch E, Andler W. Diagnostics and management of sleep-related respiratory disturbances in children with skeletal dysplasia caused by FGFR3 mutations (achondroplasia and hypochondroplasia). Georgian Med News. Jul-Aug 2011;63-72. [Medline].

  2. He X, Xie F, Ren ZR. Rapid Detection of G1138A and G1138C Mutations of FGFR3 Gene in Patients with Achondroplasia Using High-Resolution Melting Analysis. Genet Test Mol Biomarkers. Feb 17 2012;[Medline].

  3. Orioli IM, Castilla EE, Barbosa-Neto JG. The birth prevalence rates for the skeletal dysplasias. J Med Genet. Aug 1986;23(4):328-32. [Medline].

  4. Engberts AC, Jacobs WC, Castelijns SJ, Castelein RM, Vleggeert-Lankamp CL. The prevalence of thoracolumbar kyphosis in achondroplasia: a systematic review. J Child Orthop. Mar 2012;6(1):69-73. [Medline]. [Full Text].

  5. Ednick M, Tinkle BT, Phromchairak J, Egelhoff J, Amin R, Simakajornboon N. Sleep-Related Respiratory Abnormalities and Arousal Pattern in Achondroplasia during Early Infancy. J Pediatr. Jul 14 2009;[Medline].

  6. Hertel NT, Eklof O, Ivarsson S, et al. Growth hormone treatment in 35 prepubertal children with achondroplasia: a five-year dose-response trial. Acta Paediatr. Oct 2005;94(10):1402-10. [Medline].

  7. [Guideline] Trotter TL, Hall JG, American Academy of Pediatrics Committee on Genetics. Health supervision for children with achondroplasia. Pediatrics. Sep 2005;116(3):771-83. [Medline].

  8. Achondroplasia. March of Dimes. Available at http://www.marchofdimes.com/professionals/14332_1204.asp. Accessed May 8, 2009.

  9. Achondroplasia; ACH. Online Mendelian Inheritance in Man #100800. Available at www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db. Accessed April 24, 2009.

  10. Ain MC, Shirley ED. Spinal fusion for kyphosis in achondroplasia. J Pediatr Orthop. 2004;24(5):541-5. [Medline].

  11. Aldegheri R. Distraction osteogenesis for lengthening of the tibia in patients who have limb-length discrepancy or short stature. J Bone Joint Surg Am. May 1999;81(5):624-34. [Medline].

  12. Aterman K, Welch JP, Taylor PG. Presumed homozygous achondroplasia. A review and report of a further case. Pathol Res Pract. Aug 1983;178(1):27-39. [Medline].

  13. Azouz EM, Teebi AS, Eydoux P, et al. Bone dysplasias: an introduction. Can Assoc Radiol J. Apr 1998;49(2):105-9. [Medline].

  14. Bellus GA, Bamshad MJ, Przylepa KA, et al. Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN): phenotypic analysis of a new skeletal dysplasia caused by a Lys650Met mutation in fibroblast growth factor receptor 3. Am J Med Genet. Jul 2 1999;85(1):53-65. [Medline].

  15. Boor R, Fricke G, Bruhl K, Spranger J. Abnormal subcortical somatosensory evoked potentials indicate high cervical myelopathy in achondroplasia. Eur J Pediatr. Aug 1999;158(8):662-7. [Medline].

  16. Bower CM, Gungor A. Pediatric obstructive sleep apnea syndrome. Otolaryngol Clin North Am. Feb 2000;33(1):49-75. [Medline].

  17. Bulas DI, Fonda JS. Prenatal evaluation of fetal anomalies. Pediatr Clin North Am. Jun 1997;44(3):537-53. [Medline].

  18. Chitayat D, Fernandez B, Gardner A, et al. Compound heterozygosity for the Achondroplasia-hypochondroplasia FGFR3 mutations: prenatal diagnosis and postnatal outcome. Am J Med Genet. Jun 11 1999;84(5):401-5. [Medline].

  19. Defendi GL, Leung AKC. What's Your Diagnosis? Answer: Achondroplasia. Consultant for Pediatricians. February 2006;5:87-90.

  20. Deutsch ES. Tonsillectomy and adenoidectomy. Changing indications. Pediatr Clin North Am. Dec 1996;43(6):1319-38. [Medline].

  21. Ezquieta Zubicaray B, Iguacel AO, Varela Junquera JM, et al. Gly380Arg and Asn540Lys mutations of fibroblast growth factor receptor 3 in achondroplasia and hypochondroplasia in the Spanish population. Med Clin (Barc). Mar 6 1999;112(8):290-3. [Medline].

  22. Francomano CA, Ortiz de Luna RI, Hefferon TW, et al. Localization of the achondroplasia gene to the distal 2.5 Mb of human chromosome 4p. Hum Mol Genet. May 1994;3(5):787-92. [Medline].

  23. Francomano, CA. Achondroplasia. GeneReviews. Available at www.geneclinics.org/profiles/achondroplasia/details.html. Accessed April 24, 2009.

  24. Gardner RJ. A new estimate of the achondroplasia mutation rate. Clin Genet. Jan 1977;11(1):31-8. [Medline].

  25. Gordon N. The neurological complications of achondroplasia. Brain Dev. Jan 2000;22(1):3-7. [Medline].

  26. Gugliantini P, Maragliano G, Piscione M, Licata G. Constitutional osteochondrodysplasias identifiable at birth. A short review on the state of the art in radiodiagnosis in the late 20th century. Radiol Med (Torino). Mar 1999;97(3):116-20. [Medline].

  27. Hall JG, Dorst JP, Taybi H. Two probable cases of homozygosity for the achondroplasia gene. Birth Defects Orig Art Ser. 1969;4:24-34.

  28. Hall JG, Horton W, Kelly T, Scott CI. Head growth in achondroplasia: use of ultrasound studies. Am J Med Genet. Sep 1982;13(1):105. [Medline].

  29. Hecht JT, Francomano CA, Horton WA, Annegers JF. Mortality in achondroplasia. Am J Hum Genet. Sep 1987;41(3):454-64. [Medline].

  30. Hecht JT, Hood OJ, Schwartz RJ, et al. Obesity in achondroplasia. Am J Med Genet. Nov 1988;31(3):597-602. [Medline].

  31. Hecht JT, Thompson NM, Weir T, et al. Cognitive and motor skills in achondroplastic infants: neurologic and respiratory correlates. Am J Med Genet. Nov 1 1991;41(2):208-11. [Medline].

  32. Herman MJ, Pizzutillo PD. Cervical spine disorders in children. Orthop Clin North Am. Jul 1999;30(3):457-66, ix. [Medline].

  33. Horton WA. Recent milestones in achondroplasia research. Am J Med Genet A. Jan 15 2006;140(2):166-9. [Medline].

  34. Horton WA, Hood OJ, Machado MA. Growth plate cartilage studies in achondroplasia. In: Nicoletti B, Kopits SE, Ascani E, McKusick VA, eds. Human Achondroplasia: A Multidisciplinary Approach. Plenum Press; 1988:81-9.

  35. Horton WA, Rotter JI, Rimoin DL, et al. Standard growth curves for achondroplasia. J Pediatr. Sep 1978;93(3):435-8. [Medline].

  36. Huggins MJ, Smith JR, Chun K, et al. Achondroplasia-hypochondroplasia complex in a newborn infant. Am J Med Genet. Jun 11 1999;84(5):396-400. [Medline].

  37. Hunter AG, Bankier A, Rogers JG, et al. Medical complications of achondroplasia: a multicentre patient review. J Med Genet. Sep 1998;35(9):705-12. [Medline].

  38. Jones, KL. Osteochondrodysplasias. In: Smith's Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, Pennsylvania: WB Saunders Company; 1997:326-98.

  39. Keiper GL Jr, Koch B, Crone KR. Achondroplasia and cervicomedullary compression: prospective evaluation and surgical treatment. Pediatr Neurosurg. Aug 1999;31(2):78-83. [Medline].

  40. Lachman RS. Neurologic abnormalities in the skeletal dysplasias: a clinical and radiological perspective. Am J Med Genet. Mar 3 1997;69(1):33-43. [Medline].

  41. Langer LO Jr, Baumann PA, Gorlin RJ. Achondroplasia. AJR Am J Roentgenol. 1967;100:12-26.

  42. Le Merrer M, Rousseau F, Legeai-Mallet L, et al. A gene for achondroplasia-hypochondroplasia maps to chromosome 4p. Nat Genet. Mar 1994;6(3):318-21. [Medline].

  43. Lemyre E, Azouz EM, Teebi AS, et al. Bone dysplasia series. Achondroplasia, hypochondroplasia and thanatophoric dysplasia: review and update. Can Assoc Radiol J. Jun 1999;50(3):185-97. [Medline].

  44. Mancilla EE, De Luca F, Uyeda JA, et al. Effects of fibroblast growth factor-2 on longitudinal bone growth. Endocrinology. Jun 1998;139(6):2900-4. [Medline].

  45. Mogayzel PJ Jr, Carroll JL, Loughlin GM, et al. Sleep-disordered breathing in children with achondroplasia. J Pediatr. Apr 1998;132(4):667-71. [Medline].

  46. Nelson FW, Hecht JT, Horton WA, et al. Neurological basis of respiratory complications in achondroplasia. Ann Neurol. Jul 1988;24(1):89-93. [Medline].

  47. New M. Insulin-like growth factors and skeletal growth: possibilities for therapeutic interventions. J Clin Endo Metabolism. 1999;84:4351-4.

  48. Nicoletti B, Kopits SE, Ascani E, McKusick VA, eds. Human Achondroplasia: A Multidisciplinary Approach. New York:. Plenum Press;1988:3-9.

  49. Noonan KJ, Leyes M, Forriol F, Canadell J. Distraction osteogenesis of the lower extremity with use of monolateral external fixation. A study of two hundred and sixty-one femora and tibiae. J Bone Joint Surg Am. Jun 1998;80(6):793-806. [Medline].

  50. Onodera K, Niikuni N, Chigono T, et al. Sleep disordered breathing in children with achondroplasia. Part 2. Relationship with craniofacial and airway morphology. Int J Pediatr Otorhinolaryngol. Mar 2006;70(3):453-61. [Medline].

  51. Pauli RM, Scott CI, Wassman ER Jr, et al. Apnea and sudden unexpected death in infants with achondroplasia. J Pediatr. Mar 1984;104(3):342-8. [Medline].

  52. Penrose LS. Parental age in achondroplasia and mongolism. Am J Hum Genet. 1957;9:167-9.

  53. Pierre-Kahn A, Hirsch JF, Renier D, et al. Hydrocephalus and achondroplasia. A study of 25 observations. Childs Brain. 1980;7(4):205-19. [Medline].

  54. Rogers JG, Perry MA, Rosenberg LA. IQ measurement in children with skeletal dysplasia. Pediatrics. Jun 1979;63(6):894-7. [Medline].

  55. Rousseau F, Bonaventure J, Legeai-Mallet L, et al. Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia. Nature. Sep 15 1994;371(6494):252-4. [Medline].

  56. Rust OA, Perry KG Jr, Roberts WE. Tips in diagnosing fetal skeletal anomalies. Obstet Gynecol Clin North Am. Sep 1998;25(3):553-71. [Medline].

  57. Seino Y, Moriwake T, Tanaka H, et al. Molecular defects in achondroplasia and the effects of growth hormone treatment. Acta Paediatr Suppl. Feb 1999;88(428):118-20. [Medline].

  58. Seino Y, Yamanaka Y, Shinohara M, et al. Growth hormone therapy in achondroplasia. Horm Res. 2000;53 Suppl 3:53-6. [Medline].

  59. Shiang R, Thompson LM, Zhu YZ, et al. Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell. Jul 29 1994;78(2):335-42. [Medline].

  60. Shohat M, Tick D, Barakat S, et al. Short-term recombinant human growth hormone treatment increases growth rate in achondroplasia. J Clin Endocrinol Metab. Nov 1996;81(11):4033-7. [Medline].

  61. Sisk EA, Heatley DG, Borowski BJ, et al. Obstructive sleep apnea in children with achondroplasia: surgical and anesthetic considerations. Otolaryngol Head Neck Surg. Feb 1999;120(2):248-54. [Medline].

  62. Stamoyannou L, Karachaliou F, Neou P, et al. Growth and growth hormone therapy in children with achondroplasia: a two-year experience. Am J Med Genet. Oct 3 1997;72(1):71-6. [Medline].

  63. Stanescu R, Stanescu V, Maroteaux P. Homozygous achondroplasia: morphologic and biochemical study of cartilage. Am J Med Genet. Nov 1990;37(3):412-21. [Medline].

  64. Stokes DC, Phillips JA, Leonard CO, et al. Respiratory complications of achondroplasia. J Pediatr. Apr 1983;102(4):534-41. [Medline].

  65. Stoll C, Dott B, Roth MP, Alembik Y. Birth prevalence rates of skeletal dysplasias. Clin Genet. Feb 1989;35(2):88-92. [Medline].

  66. Tasker RC, Dundas I, Laverty A, et al. Distinct patterns of respiratory difficulty in young children with achondroplasia: a clinical, sleep, and lung function study. Arch Dis Child. Aug 1998;79(2):99-108. [Medline].

  67. Tavormina PL, Bellus GA, Webster MK, et al. A novel skeletal dysplasia with developmental delay and acanthosis nigricans is caused by a Lys650Met mutation in the fibroblast growth factor receptor 3 gene. Am J Hum Genet. Mar 1999;64(3):722-31. [Medline].

  68. Thompson NM, Hecht JT, Bohan TP, et al. Neuroanatomic and neuropsychological outcome in school-age children with achondroplasia. Am J Med Genet. Apr 16 1999;88(2):145-53. [Medline].

  69. Todorov AB, Scott CI Jr, Warren AE, Leeper JD. Developmental screening tests in achondroplastic children. Am J Med Genet. 1981;9(1):19-23. [Medline].

  70. Velinov M, Slaugenhaupt SA, Stoilov I, et al. The gene for achondroplasia maps to the telomeric region of chromosome 4p. Nat Genet. Mar 1994;6(3):314-7. [Medline].

  71. Wang Y, Spatz MK, Kannan K, et al. A mouse model for achondroplasia produced by targeting fibroblast growth factor receptor 3. Proc Natl Acad Sci U S A. Apr 13 1999;96(8):4455-60. [Medline].

  72. Weber G, Prinster C, Meneghel M, et al. Human growth hormone treatment in prepubertal children with achondroplasia. Am J Med Genet. Feb 2 1996;61(4):396-400. [Medline].

  73. Wilkin DJ, Szabo JK, Cameron R, et al. Mutations in fibroblast growth-factor receptor 3 in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome. Am J Hum Genet. Sep 1998;63(3):711-6. [Medline].

  74. Yang SS, Corbett DP, Brough AJ, et al. Upper cervical myelopathy in achondroplasia. Am J Clin Pathol. Jul 1977;68(1):68-72. [Medline].

 
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Height for females with achondroplasia (mean/standard deviation [SD]) compared to normal standard curves. The graph is based on information from 214 females. Adapted from Horton WA, Rotter JI, Rimoin DL, et al. Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.
Height for males with achondroplasia (mean/2 standard deviations [SDs]) compared to normal standard curves. The graph is based on information from 189 males. Adapted from Horton WA, Rotter JI, Rimoin DL, et al: Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.
Mean growth velocities (solid line) for males (top) and females (bottom) with achondroplasia compared to normal growth velocity curves. Dashed lines indicate third percentile, mean, and 97th percentile. Data are from 26 males and 35 females. Adapted from Horton WA, Rotter JI, Rimoin DL, et al. Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.
Upper and lower segment lengths for males (top) and (bottom) with achondroplasia (mean/standard deviation [SD]). Data are from 75 males and 95 females. Adapted from Horton WA, Rotter JI, Rimoin DL, et al. Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.
Head circumference for females with achondroplasia compared to normal curves (dashed lines). Data are from 145 females. Adapted from Horton WA, Rotter JI, Rimoin DL, et al. Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.
Head circumference for males with achondroplasia compared to normal curves (dashed lines). Data are from 114 females. Adapted from Horton WA, Rotter JI, Rimoin DL, et al. Standard growth curves for achondroplasia. J Pediatr. 1978 Sep; 93(3): 435-8.
 
 
 
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