Genetics of Achondroplasia Clinical Presentation

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

History

Achondroplasia is primarily due to a de novo mutation; however, some parents who are affected are heterozygous for either the G1138A or G1138C mutation. Identifying families members at risk is helpful in addressing medical treatment plans, offering genetic counseling with options for genetic testing, and providing educational materials and emotional support.

Once the diagnosis of achondroplasia is made, obtain the following history to avoid serious complications:

  • A history of pain, ataxia, incontinence, and apnea may be due to cervicomedullary compression. Cord compression can cause respiratory arrest and progressive quadriparesis. Indications for surgery to release the compression include brisk reflexes, a small foramen magnum, and central hypopnea.
  • Obtain a careful history for recurrent otitis media to prevent conductive hearing loss which can be the cause of language delays.
  • A history of sleep disturbances[5] and increased head size may indicate neurologic and respiratory complications.
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Physical

  • Neurologic findings
    • Hypotonia in infancy and early childhood
    • Delayed motor milestones
    • Normal intelligence with possible minor deficit in visual-spatial tasks
  • Craniofacial features:
    • Large calvarial bones in contrast to the small cranial base and facial bones
    • True megalencephaly (large head) with frontal bossing
    • Midface hypoplasia
    • Dental malocclusion and crowding
  • Skeletal features:
    • Disproportionate short stature: The average adult male height is 131 ± 5.6 cm; the average adult female height is 124 ± 5.9 cm (approximately 4 ft for both men and women).
    • Normal trunk length that appears long and narrow, small thoracic cage
    • Rhizomelic shortening of the proximal limbs with redundant skin folds
    • Brachydactyly and trident hand configuration: A marked separation between the ring and middle fingers giving the hand a 3-pronged appearance.
    • Thoracolumbar gibbus (lumbar kyphosis) in infancy, which is replaced by an exaggerated lumbar lordosis once ambulation begins
    • Hyperextensibility of most joints, especially the knees.
    • Limited elbow extension and rotation
    • Genu varum (bow legs)
  • Radiographic findings
    • Contracted skull base
    • Progressive interpedicular narrowing in the lumbar spine region
    • Short pedicles which can cause spinal stenosis
    • Short femoral neck and metaphyseal flaring
    • Dysplastic ilium, narrow sacroiliac groove, flat-roofed acetabula
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Causes

  • Advanced paternal age (age >35 y) is identified as a risk factor in de novo cases of achondroplasia, suggesting that factors influencing DNA replication or repair during spermatogenesis may predispose men to the occurrence of G1138 FGFR3 mutations.
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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.

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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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