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Genetics of Achondroplasia Differential Diagnoses

  • Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Maria Descartes, MD  more...
 
Updated: Jan 28, 2016
 
 

Diagnostic Considerations

The phenotype and radiographic findings of achondroplasia are distinctive; diagnosis of affected children should not be difficult. However, there are other types of short-limb dwarfism associated with mutations within FGFR3. Diagnostic testing by genetic molecular studies is available for confirmation.

Hypochondroplasia

This chondrodysplasia occurs less often than achondroplasia. Hypochondroplasia differs from achondroplasia in its the lack of craniofacial involvement and milder phenotypic changes in the spine and hands. Inheritance is autosomal dominant, and the gene has been mapped to 4p16.3, but with a different mutational change within FGFR3.

However, a study by Xue et al suggested that a great amount of overlap exists between the genotypes and phenotypes of achondroplasia and hypochondroplasia, indicating that when either disorder is suspected, mutation testing for both should be performed.[19]

SADDAN (severe achondroplasia with developmental delay and acanthosis nigricans)

Extremely short stature, profound developmental delay, marked tibial bowing, and acanthosis nigricans characterize this rare genetic disorder.

Thanatophoric dysplasia

This is a skeletal dysplasia with significant newborn mortality due to a small thoracic cage and pulmonary insufficiency. Patients who survive beyond the neonatal period have profound developmental delay and severe growth deficiency. It is inherited as an autosomal dominant trait; all cases are due to a de novo mutation.

Differential Diagnoses

 
 
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

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.

Lois J Starr, MD, FAAP Assistant Professor of Pediatrics, Clinical Geneticist, Munroe Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center

Lois J Starr, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

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 and Translational Research, College of American Pathologists

Disclosure: Nothing to disclose.

Acknowledgements

The authors and editors of Medscape Reference 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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