eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Genetics

Achondrogenesis: 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: Apr 23, 2009

Follow-up

Prognosis

  • Achondrogenesis is universally lethal.

Patient Education

  • Current information about the syndrome should be made available to the families.
  • Families may be referred to the following groups for helpful information and support:

Miscellaneous

Medicolegal Pitfalls

  • Failure to refer to clinical geneticists and physicians who are experienced in lethal skeletal dysplasias for diagnosis
  • Failure to give genetic counseling after confirmation of diagnosis

Special Concerns

  • Prenatal diagnosis by ultrasonography
    • Experienced ultrasonographers can recognize various types of achondrogenesis in fetuses as early as 12–14 weeks' gestation. This makes ultrasonography an acceptable option when molecular studies are unavailable or unfeasible.
    • Achondrogenesis, a lethal form of congenital chondrodystrophy, is characterized by extreme micromelia. The prenatal diagnosis of achondrogenesis is based on extreme micromelia, narrow thorax, and poor mineralization of the skull and vertebrae. Other ultrasonic features include polyhydramnios, large head, nuchal edema, reduced rump length, and poor ossification of vertebral bodies and limb tubular bones (leading to difficulties in determining their length).8,10
    • Characterization of demineralization is important in differentiating between type I and II achondrogenesis.10 When the demineralization affects the skull and iliac wings, the presumptive diagnosis is type I; when the skull appears normally mineralized the presumptive diagnosis is type II. When demineralization is present on ultrasonography, radiographic findings may confirm it. However, in the absence of demineralization on ultrasonography, radiological demineralization cannot be presumed. Because the recognition of demineralization by ultrasonography is fraught with false negatives, a tendency to overreport the type II form is noted.8
    • Achondrogenesis type I should be strongly suspected when ultrasonography reveals an extremely echo-poor appearance of the skeleton and a poorly mineralized skull, as well as short limbs and rib fractures.
  • Prenatal diagnosis by molecular studies
    • Prenatal diagnosis of achondrogenesis type IB and type II may be accomplished by mutation analysis of chorionic villus DNA or amniocyte DNA in the first or second trimester, respectively.
    • In achondrogenesis type IB, both alleles of DDST should be characterized beforehand, and the source parent of each allele identified. Theoretically, analysis of sulfate incorporation in chorionic villi might be used for prenatal diagnosis, but experience is lacking.
    • In achondrogenesis type II, the affected fetus usually has a new dominant mutation of the COL2A1 gene. Asymptomatic carriers may be present in families of an affected patient. Prenatal diagnosis may be possible if the mutation has been characterized in the affected family.
  • Genetic counseling
    • Recurrence risk is 25% for achondrogenesis type IA and type IB.
    • Achondrogenesis type II is usually caused by a new dominant mutation; however, asymptomatic carriers may be present in the family.
    • Recurrence of achondrogenesis type II within the same family is evidence for germline mosaicism.
      • Germline mosaicism for a dominant mutation in one parent can mimic autosomal recessive inheritance when two or more children are born to apparently normal parents.
      • In the case of germline mosaicism, phenotypically normal individuals may transmit several gametes that are clonal descendants of a single progenitor cell, in which a de novo mutation occurred during early embryonic development.11
      • In the case of somatic mosaicism, the manifestation of such a mutation in a mosaic parent may range from none or minimal to a severe generalized effect. It could also result in a milder but different phenotype, such as the observations of severe Kniest dysplasia in two unrelated children with COL2A1 mutations and mild Stickler syndrome or spondyloepiphyseal dysplasia in their mosaic parents.12
      • Germline or somatic mosaicism has been documented in other autosomal dominant skeletal dysplasias, such as achondroplasia,13 pseudoachondroplasia, and osteogenesis imperfecta.14
      • The possibility of germline mosaicism should always be considered in case of an apparently de novo dominant mutation, and the family should not be counseled that the recurrence risk is zero.
      • Estimating the exact recurrence risk for healthy parents with only one child affected, although this risk is quite low considering that achondrogenesis type II/hypochondrogenesis is not that infrequent and no other written reports of recurrence are noted.15
    • Prenatal diagnosis is possible in the first and second trimester by prenatal ultrasonography and molecular analysis.
 


More on Achondrogenesis

Overview: Achondrogenesis
Differential Diagnoses & Workup: Achondrogenesis
Treatment & Medication: Achondrogenesis
Follow-up: Achondrogenesis
Multimedia: Achondrogenesis
References
Further Reading
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References

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Further Reading

Guidelines have been established for prenatal screening and diagnosis for pediatricians. 16

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Keywords

achondrogenesis type I, Fraccaro-Houston-Harris type achondrogenesis, achondrogenesis type IA, Houston-Harris type achondrogenesis, achondrogenesis type IB, Fraccaro type achondrogenesis, achondrogenesis type II, Langer-Saldino type achondrogenesis, achondrogenesis type III, achondrogenesis type IV, achondrogenesis-hypochondrogenesis type II, chondrodysplasias, hypochondrogenesis, micromelia, CIfemur, atelosteogenesis type II, diastrophic dysplasia, neonatal dwarfism, patent ductus arteriosus, atrial septal defect, ventricular septal defect, rib fractures, osteoarthritis, polyhydramnios, hydrops fetalis, breech presentation, lethal neonatal dwarfism, treatment, diagnosis

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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

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.

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, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics and Rehabilitation, 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.

 
 
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