A genetic approach to the diagnosis of skeletal dysplasia

The skeletal dysplasias are a large and heterogeneous group of disorders. Currently, there are more than 100 recognized forms of skeletal dysplasia, which makes arriving at a specific diagnosis difficult. This process is additionally complicated by the rarity of the individual conditions. The establishment of a precise diagnosis is important for numerous reasons, including prediction of adult height, accurate recurrence risk, prenatal diagnosis in future pregnancies, and most importantly, for proper clinical treatment. When a child is referred for genetic evaluation of suspected skeletal dysplasia, clinical and radiographic indicators, and more specific biochemical and molecular tests, are used to try to arrive at the underlying diagnosis. Preferably, the clinical features and pattern of radiographic abnormalities are used to generate a differential diagnosis so that the appropriate confirmatory tests can be done. The current author will review this sequence of diagnostic steps. For geneticists, this process starts with history gathering including the prenatal and family history. This is followed by clinical examination with measurements and radiographs. Only once a limited differential diagnosis has been established, should molecular investigations be considered.