eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Genetics

Skeletal Dysplasia: Follow-up

Author: Harold Chen, MD, MS, FAAP, FACMG, Professor, Departments of Pediatrics, Obstetrics and Gynecology, and Pathology, Director of Genetic Laboratory Services, Louisiana State University Medical Center
Contributor Information and Disclosures

Updated: Sep 14, 2009

Follow-up

Further Outpatient Care

  • To prevent inappropriate counseling, do not offer genetic counseling until the diagnosis is confirmed by a clinician experienced in skeletal dysplasias.
    • In an autosomal dominant disorder, the risk that an affected parent will have an affected child is 50%. For unaffected parents, the risk is negligible, except when germinal mosaicism occurs.
    • When both parents have the same autosomal dominant condition, such as achondroplasia, the offspring have (1) a 25% chance of having normal stature, (2) a 50% chance of having typical achondroplasia, and (3) a 25% chance of having homozygous achondroplasia, which is lethal.
    • When one parent has an autosomal dominant skeletal dysplasia condition (eg, achondroplasia) and the other parent has a different autosomal dominant skeletal dysplasia (eg, hypochondroplasia) the offspring have (1) a 25% chance of having normal stature, (2) a 25% chance of having achondroplasia, (3) a 25% chance of having hypochondroplasia, and (4) a 25% chance of having heterozygous for the achondroplasia-hypochondroplasia compound with intermediate severity.
    • In an autosomal recessive disorder, the parents are obligatory carriers with a 25% risk that each child will have the disorder.
    • In an X-linked recessive disorder in which the mother is a carrier, a male child has a 50% risk of being affected and a female child has a 50% risk of being a carrier.
  • Assistance with research and diagnosis is available from various organizations. Cedars-Sinai Medical Center is a referral center for the diagnosis, management, and etiology of skeletal dysplasia. The contact information is as follows: International Skeletal Dysplasia Registry
    Medical Genetics Institute
    8700 Beverly Blvd
    West Tower, Suite 665
    Los Angeles, CA 90048
    Phone: 800-CEDARS-1 (800-233-2771) or 310-423-9915
    email: MaryAnn.Priore@cshs.org

Complications

  • Intrauterine complications: Polyhydramnios and fetal hydrops are typically seen in patients with lethal types of chondrodystrophy, such as achondrogenesis or thanatophoric dysplasia. Occasionally, polyhydramnios may be seen in patients with nonlethal types of chondrodystrophy, such as achondroplasia.
  • Respiratory complications: Respiratory distress secondary to small chest, small lungs, small or collapsing trachea, or small upper airway is seen in patients with many types of chondrodystrophy, such as asphyxiating thoracic dystrophy. Infants may snore, may have upper airway obstruction, or may experience hypoxic episodes.
  • CNS complications: Hydrocephalus can occur in several types of skeletal dysplasia, notably in achondroplasia, metatropic dysplasia, and other conditions that affect the base of the skull, resulting in small foramen magnum and jugular foramen.
  • Skeletal complications: Instability of the C1-C2 cervical spine that leads to spinal cord compression or nerve damage may be observed in patients with several types of chondrodystrophy, such as achondroplasia, SED congenita, and Morquio syndrome. Vertebral abnormalities, hip dysplasia, tight and loose joints, osteoarthritis, bowed legs, and fractures may vary.
  • Muscular complications: Truncal hypotonia may lead to kyphoscoliosis in infants with achondroplasia or mucopolysaccharidoses. Thoracolumbar kyphosis may revert to marked lordosis in achondroplasia.
  • Otolaryngologic complications: Progressive deafness is associated with repeated middle ear infections in patients with diastrophic dysplasia and achondroplasia. Hearing loss can be conductive or neurosensory in origin.
  • Ophthalmologic complications: Myopia may predispose the patient to retinal detachment in Kniest dysplasia and SED congenita.
  • Dental complications: Malocclusions, dental crowding, and structural abnormalities of teeth may be present in patients with many types of chondrodystrophy.
  • Nutritional complications: Obesity is often a problem in patients with some types of chondrodystrophy, especially achondroplasia.
  • Other complications
    • Anesthesia can be a problem in patients with some chondrodysplasias.
    • Unstable cervical vertebrae should be excluded.
    • Malignant hyperthermia may occur during anesthesia in patients with some types of chondrodysplasia, such as osteogenesis imperfecta.
    • Numerous obstetric and gynecologic problems are common in women with disproportionately short stature. Cesarean delivery of a baby may be required because of a contracted pelvis in the mother.

Prognosis

  • Although certain skeletal dysplasias are lethal in the newborn or infancy periods, patients with other types of skeletal dysplasia have normal or near-normal life expectancy. For patients with nonlethal skeletal dysplasias, prognosis depends on the degree of skeletal abnormalities and concomitant anomalies.
  • Some patients may have difficulty finding a marital partner.
  • Men with skeletal dysplasia complain less often of psychiatric symptoms and feel less stigmatized than do women.
  • Medical and social aspects of the life course for adults with a skeletal dysplasia include the following:22
    • Overall, strong evidence suggests some barriers to equal opportunity in education and employment, and these, together with increased social isolation, are highly likely to exert a strong influence on financial situation and, therefore, on quality of life. All persons with skeletal dysplasia are physically impaired by virtue of the dysplasia. Only those with severe physical abnormalities are hampered in obtaining education and employment.
    • A substantial gap is observed in knowledge of the medical and social experiences of adults with skeletal dysplasias.
    • The relevance of the disability label is an important issue to many people with disabling conditions. It may be necessary to "come out" as disabled in order to qualify for support such as Disability Living Allowance (DLA).
    • Only by adopting a more stringent methodological approach to future research will it be possible to provide the robust evidence-base needed to inform future health and social service provision, as well as offering material for education and training purposes.

Patient Education

The birth of a child with a skeletal dysplasia is an emotionally difficult experience for parents. The term "dwarf" has especially negative connotations; thus, skeletal dysplasia is the preferred term for discussing these disorders. Up-to-date information and resources pertaining to skeletal dysplasia should be made available to families. The following resources may help parents meet other parents of children with skeletal dysplasia who can offer support and realistic appraisal of the implications:

Miscellaneous

Medicolegal Pitfalls

  • Diagnosis based on traditional clinical, radiographic, and pathologic methods is almost impossible if a pregnancy has been terminated using destructive methods.
  • Refer patients to clinical geneticists and physicians experienced in skeletal dysplasias for diagnosis and genetic counseling.
  • The diagnosis of achondroplasia may not be apparent in the neonate because the birth length of an infant with achondroplasia may not be below the fifth percentile.

Special Concerns

  • Prenatal diagnosis
    • Prenatal ultrasonography can identify most fetuses with skeletal dysplasia by identification of short limbs and other skeletal and nonskeletal anomalies.
    • Currently, certain disorders, such as achondroplasia, can be diagnosed prenatally by using DNA testing of FGFR3 mutations of fetal cells obtained from amniocentesis or chorionic villus sampling.
    • When one or both parents have an autosomal dominant type of skeletal dysplasia, the pregnancy is at high risk. In such situations, disease-causing mutations in the affected parent(s) should be identified prior to prenatal testing.
    • Prenatal diagnosis provides families with reproductive options, ie, elective termination of pregnancy for the lethal and most severe skeletal dysplasias or continuation of pregnancy for optimal perinatal care.
 


More on Skeletal Dysplasia

Overview: Skeletal Dysplasia
Differential Diagnoses & Workup: Skeletal Dysplasia
Treatment & Medication: Skeletal Dysplasia
Follow-up: Skeletal Dysplasia
Multimedia: Skeletal Dysplasia
References
[ CLOSE WINDOW ]

References

  1. International Working Group on Constitutional Diseases of Bone. International nomenclature and classification of the osteochondrodysplasias (1997). Am J Med Genet. Oct 12 1998;79(5):376-82. [Medline].

  2. Ikegawa S. Genetic analysis of skeletal dysplasia: recent advances and perspectives in the post-genome-sequence era. J Hum Genet. 2006;51(7):581-6. [Medline].

  3. Hopyan S, Gokgoz N, Poon R, Gensure RC, Yu C, Cole WG. A mutant PTH/PTHrP type I receptor in enchondromatosis. Nat Genet. Mar 2002;30(3):306-10. [Medline].

  4. Alman BA. Skeletal dysplasias and the growth plate. Clin Genet. Jan 2008;73(1):24-30. [Medline].

  5. Kronenberg HM. Developmental regulation of the growth plate. Nature. May 15 2003;423(6937):332-6. [Medline].

  6. Shiang R, Thompson LM, Zhu YZ, Church DM, Fielder TJ, Bocian M. 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].

  7. Blomstrand S, Claesson I, Save-Soderbergh J. A case of lethal congenital dwarfism with accelerated skeletal maturation. Pediatr Radiol. 1985;15(2):141-3. [Medline].

  8. Gordon SL, Varano LA, Alandete A, Maisels MJ. Jansen's metaphyseal dysostosis. Pediatrics. Oct 1976;58(4):556-60. [Medline].

  9. Jobert AS, Zhang P, Couvineau A, Bonaventure J, Roume J, Le Merrer M. Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia. J Clin Invest. Jul 1 1998;102(1):34-40. [Medline].

  10. Schipani E, Kruse K, Jüppner H. A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia. Science. Apr 7 1995;268(5207):98-100. [Medline].

  11. Mundlos S, Otto F, Mundlos C, Mulliken JB, Aylsworth AS, Albright S. Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia. Cell. May 30 1997;89(5):773-9. [Medline].

  12. Baitner AC, Maurer SG, Gruen MB, Di Cesare PE. The genetic basis of the osteochondrodysplasias. J Pediatr Orthop. Sep-Oct 2000;20(5):594-605. [Medline].

  13. Superti-Furga A, Bonafe L, Rimoin DL. Molecular-pathogenetic classification of genetic disorders of the skeleton. Am J Med Genet. Winter 2001;106(4):282-93. [Medline].

  14. Rimoin DL, Cohn D, Krakow D, Wilcox W, Lachman RS, Alanay Y. The skeletal dysplasias: clinical-molecular correlations. Ann N Y Acad Sci. Nov 2007;1117:302-9. [Medline].

  15. Superti-Furga A, Unger S, and the Nosology Group of theInternational Skeletal Dysplasia Society. Nosology and classification of geneticskeletal disorders: 2006 revision. Am J Med Genet Part A. 2007;143A:1-18.

  16. Doray B, Favre R, Viville B, Langer B, Dreyfus M, Stoll C. Prenatal sonographic diagnosis of skeletal dysplasias. A report of 47 cases. Ann Genet. Jul-Dec 2000;43(3-4):163-9. [Medline].

  17. Parilla BV, Leeth EA, Kambich MP, Chilis P, MacGregor SN. Antenatal detection of skeletal dysplasias. J Ultrasound Med. Mar 2003;22(3):255-8; quiz 259-61. [Medline].

  18. Krakow D, Williams J 3rd, Poehl M, Rimoin DL, Platt LD. Use of three-dimensional ultrasound imaging in the diagnosis of prenatal-onset skeletal dysplasias. Ultrasound Obstet Gynecol. May 2003;21(5):467-72. [Medline].

  19. Cassart M, Massez A, Cos T, et al. Contribution of three-dimensional computed tomography in the assessment of fetal skeletal dysplasia. Ultrasound Obstet Gynecol. May 2007;29(5):537-43. [Medline].

  20. Teele RL. A guide to the recognition of skeletal disorders in the fetus. Pediatr Radiol. Jun 2006;36(6):473-84. [Medline].

  21. [Guideline] Krakow D, Lachman RS, Rimoin DL. Guidelines for the prenatal diagnosis of fetal skeletal dysplasias. Genet Med. Feb 2009;11(2):127-33. [Medline].

  22. Thompson S, Shakespeare T, Wright MJ. Medical and social aspects of the life course for adults with a skeletaldysplasia: A review of current knowledge. Disabil Rehab. 2008;30:1-12.

  23. Bethem D, Winter RB, Lutter L, et al. Spinal disorders of dwarfism. Review of the literature and report of eighty cases. J Bone Joint Surg Am. Dec 1981;63(9):1412-25. [Medline].

  24. Bonnefoy O, Delbosc JM, Maugey-Laulom B, Lacombe D, Gaye D, Diard F. Prenatal diagnosis of hypochondroplasia: three-dimensional multislice computed tomography findings and molecular analysis. Fetal Diagn Ther. 2006;21(1):18-21. [Medline].

  25. Bridges NA, Brook CG. Progress report: growth hormone in skeletal dysplasia. Horm Res. 1994;42(4-5):231-4. [Medline].

  26. Chen H. Atlas of Genetic Diagnosis and Counseling. Totowa, New Jersey: Humana Press; 2006:1-1076.

  27. Chen H. Genetic disorders. In: Liu PI, ed. Blue Book of Diagnostic Tests. Philadelphia, PA: WB Saunders Co; 1986:421-62.

  28. Chen H. Skeletal dysplasias and mental retardation. In: Papadatos CJ, Bartsocas CS, eds. Skeletal Dysplasias. 1982. New York, NY: Alan R Liss Inc; 451-85.

  29. Clark RN. Congenital dysplasias and dwarfism. Pediatr Rev. Nov 1990;12(5):149-59. [Medline].

  30. Cohen MM Jr. The new bone biology: pathologic, molecular, and clinical correlates. Am J Med Genet A. Dec 1 2006;140(23):2646-706. [Medline].

  31. Cormier-Daire V, Huber C, Munnich A. Allelic and nonallelic heterogeneity in dyschondrosteosis (Leri-Weill syndrome). Am J Med Genet. Winter 2001;106(4):272-4. [Medline].

  32. Dominguez R, Talmachoff P. Diagnostic imaging update in skeletal dysplasias. Clin Imaging. Jul-Sep 1993;17(3):222-34. [Medline].

  33. Dorst JP, Scott CI Jr, Hall JG. The radiologic assessment of short stature--dwarfism. Radiol Clin North Am. Aug 1972;10(2):393-414. [Medline].

  34. Folstein SE, Weiss JO, Mittelman F, Ross DJ. Impairment, psychiatric symptoms, and handicap in dwarfs. Johns Hopkins Med J. Jun 1981;148(6):273-7. [Medline].

  35. Fukami M, Okuyama T, Yamamori S, Nishimura G, Ogata T. Microdeletion in the SHOX 3' region associated with skeletal phenotypes of Langer mesomelic dysplasia in a 45,X/46,X,r(X) infant and Leri-Weill dyschondrosteosis in her 46,XX mother: implication for the SHOX enhancer. Am J Med Genet A. Aug 15 2005;137(1):72-6. [Medline].

  36. Garjian KV, Pretorius DH, Budorick NE, Cantrell CJ, Johnson DD, Nelson TR. Fetal skeletal dysplasia: three-dimensional US--initial experience. Radiology. Mar 2000;214(3):717-23. [Medline].

  37. Hall JG, Rimoin DL. Medical complications of dwarfing syndromes. In: Growth, Genetics and Hormones. Vol 4. 1988:6-9.

  38. Hunter AG. Some psychosocial aspects of nonlethal chondrodysplasias: I. Assessment using a Life-Styles Questionnaire. Am J Med Genet. Jun 16 1998;78(1):1-8. [Medline].

  39. Hurst JA, Firth HV, Smithson S. Skeletal dysplasias. Semin Fetal Neonatal Med. Jun 2005;10(3):233-41. [Medline].

  40. Ilizarov GA. Clinical application of the tension-stress effect for limb lengthening. Clin Orthop. Jan 1990;(250):8-26. [Medline].

  41. Jia L, Ho NC, Park SS, et al. Comprehensive resource: Skeletal gene database. Am J Med Genet. Winter 2001;106(4):275-81. [Medline].

  42. Kennelly MM, Moran P. A clinical algorithm of prenatal diagnosis of Radial Ray Defects with two and three dimensional ultrasound. Prenat Diagn. Aug 2007;27(8):730-7. [Medline].

  43. Lachman RS. International nomenclature and classification of the osteochondrodysplasias (1997). Pediatr Radiol. Oct 1998;28(10):737-44. [Medline].

  44. Lachman RS, Rappaport V. Fetal imaging in the skeletal dysplasias. Clin Perinatol. Sep 1990;17(3):703-22. [Medline].

  45. Leka SK, Kitsiou-Tzeli S, Kalpini-Mavrou A, Kanavakis E. Short stature and dysmorphology associated with defects in the SHOX gene. Hormones (Athens). Apr-Jun 2006;5(2):107-18. [Medline].

  46. Ngo C, Viot G, Aubry MC, et al. First-trimester ultrasound diagnosis of skeletal dysplasia associated with increased nuchal translucency thickness. Ultrasound Obstet Gynecol. Aug 2007;30(2):221-6. [Medline].

  47. 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].

  48. Rimoin DL. Molecular defects in the chondrodysplasias. Am J Med Genet. May 3 1996;63(1):106-10. [Medline].

  49. Rimoin DL, Lachman R, Unger S. Chondrodysplasias. In: Emery and Rimoin's Principles and Practice of Medical Genetics. Vol 3. 4th ed. London, England: Churchill Livingstone; 2002:4071-115.

  50. Rimoin DL, Lachman RS. Genetic disorders of the osseous skeleton. In: Beighton P, ed. McKusick's Heritable Disorders of Connective Tissue. 5th ed. Mosby-Year Book; 1993:557-689.

  51. Romero R, Athanassiadis AP, Jeanty P. Fetal skeletal anomalies. Radiol Clin North Am. Jan 1990;28(1):75-99. [Medline].

  52. Ruano R, Molho M, Roume J, Ville Y. Prenatal diagnosis of fetal skeletal dysplasias by combining two-dimensional and three-dimensional ultrasound and intrauterine three-dimensional helical computer tomography. Ultrasound Obstet Gynecol. Aug 2004;24(2):134-40. [Medline].

  53. Sillence DO, Rimoin DL, Lachman R. Neonatal dwarfism. Pediatr Clin North Am. Aug 1978;25(3):453-83. [Medline].

  54. Spirt BA, Oliphant M, Gottlieb RH, Gordon LP. Prenatal sonographic evaluation of short-limbed dwarfism: an algorithmic approach. Radiographics. Mar 1990;10(2):217-36. [Medline].

  55. Unger S, Hecht JT. Pseudoachondroplasia and multiple epiphyseal dysplasia: New etiologic developments. Am J Med Genet. Winter 2001;106(4):244-50. [Medline].

  56. Yang SS. Skeletal system: Osteochondrodysplasias and dysostoses. In: Gilbert-Barness E, ed. Potter's Pathology of the Fetus and Infant. Vol 2. St Louis, Mo: Mosby-Year Book; 1997:1423-78.

  57. Yasui N, Kawabata H, Kojimoto H, et al. Lengthening of the lower limbs in patients with achondroplasia and hypochondroplasia. Clin Orthop. Nov 1997;(344):298-306. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

skeletal dysplasia, disproportional short stature, short stature, dwarfism, osteochondrodysplasias, thanatophoric dysplasia, achondroplasia, osteogenesis imperfecta, achondrogenesis, chondrodysplasia punctata, homozygous achondroplasia, chondrodysplasia punctata, camptomelic dysplasia, congenital lethal hypophosphatasia, perinatal lethal type of osteogenesis imperfecta, short-rib polydactyly syndromes, hypochondroplasia, rhizomelic type of chondrodysplasia punctata, Jansen-type metaphyseal dysplasia, spondyloepiphyseal dysplasia congenita, atelosteogenesis, diastrophic dysplasia, congenital short femur, Langer-type mesomelic dysplasia, Nievergelt-type mesomelic dysplasia, Robinow syndrome, Reinhardt syndrome, acrodysostosis, peripheral dysostosis, Kniest dysplasia, fibrochondrogenesis, Roberts syndrome, acromesomelic dysplasia, micromelia, Morquio syndrome, Kniest syndrome, metatrophic dysplasia, spondyloepimetaphyseal dysplasia

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Harold Chen, MD, MS, FAAP, FACMG, Professor, Departments of Pediatrics, Obstetrics and Gynecology, and Pathology, Director of Genetic Laboratory Services, Louisiana State University Medical Center
Harold Chen, MD, MS, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Society of Human Genetics, and Teratology Society
Disclosure: Nothing to disclose.

Medical Editor

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.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

David Flannery, MD, FAAP, FACMG, Vice Chair of Education, Chief, Section of Medical Genetics, Professor, Department of Pediatrics, Medical College of Georgia
David Flannery, MD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics and American College of Medical Genetics
Disclosure: Nothing to disclose.

CME Editor

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 of Genetics, Munroe Meyer Institute, Professor, Department of Pediatrics, Pathology and Microbiology, 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.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.