Genetics of Achondroplasia Differential Diagnoses

Updated: Sep 02, 2016
  • Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Maria Descartes, MD  more...
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Diagnostic ConsiderationsHypochondroplasiaSADDAN (severe achondroplasia with developmental delay and acanthosis nigricans)Thanatophoric dysplasia

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.

This chondrodysplasia occurs less often than achondroplasia. Hypochondroplasia differs from achondroplasia in its 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. A study by Xue et al suggests that significant overlap exists between the genotypes and phenotypes of achondroplasia and hypochondroplasia, indicating that when either disorder is suspected, molecular genetic testing for both should be performed. [19]

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

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