Background: Fetal skeleton develops early in the fetal period. The appendicular and the axial skeleton undergo a programmed pattern of endochondral ossification, whereas the calvarium and portions of the clavicle and pubic bone ossify via membranous ossification. Disruption of the molecular mechanisms fine-tuning this process leads to osteo-chondrodysplasias (skeletal dysplasias) or dysostoses, namely genetic skeletal disorders. The 2015 revision of the Nosology and Classification of Genetic Skeletal Disorders provides a list of 436 disorders in 42 groups, and 364 related genes.
Objective and hypotheses: Diagnosis of prenatal-onset genetic bone diseases mandates radiographic, clinical and molecular assessment. The combined use of these methods is essential for appropriate counselling of the parents. Information regarding the severity and natural history of an individual disorder is critical for the families and medical care providers.
Method: In general, prenatal ultrasound (US) is currently the accepted modality for fetal assessment. Lethality should be determined based on US parameters and/or by molecular diagnosis. Those with a non-lethal condition may further be described as mild or severe. First trimester US, usually used for aneuploidy screening can identify severe, usually lethal skeletal dysplasias. Others are detected in the late second trimester, the remaining diagnosed in the third trimester or at birth. Imaging strategies have evolved in the last decade. Three-dimentional (3D) US is helpful in depicting and characterisation of the specific entity. Fetal magnetic resonance imaging (MRI) has also been documented to be useful for analysis of fetal spine and concurrent malformations. The most recent method is using 3D reconstructions of low dose computerized tomography images for prenatal evaluation.
Results: The diagnosis of a genetic skeletal disorder is ideally made in the prenatal period to ensure accurate genetic counselling and provide a management plan before and after delivery. Imaging strategies are discussed with respect to possible outcome.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology