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Approach to prenatal diagnosis of the lethal skeletal dysplasias

Phyllis Glanc, MD, FRCPC
Section Editors
Deborah Levine, MD
Louise Wilkins-Haug, MD, PhD
Deputy Editor
Vanessa A Barss, MD, FACOG


Skeletal dysplasias or osteochondrodysplasia are a large, heterogeneous group of conditions involving the formation and growth of bone. Some skeletal dysplasias are associated with abnormalities in other organ systems.

These disorders begin to manifest in the early stages of fetal development. They can be due to extrinsic causes (eg, teratogen exposure, maternal autoimmune disorders) or intrinsic causes (single gene disorders with autosomal dominant, recessive, or X-linked modes of inheritance; imprinting errors or chromosome abnormalities) [1]. In view of the large number of skeletal dysplasias (over 436 known types), a nosology and classification system was developed that categorizes genetic bone disorders into 42 major groups based on their cardinal features (eg, radiological findings, molecular etiology, inheritance) [2-4] to facilitate diagnosis [5].

The lethal group of skeletal dysplasias typically has an earlier onset with more severe phenotypic features than the non-lethal group, thus lethal skeletal dysplasia are potentially more amenable to prenatal diagnosis [6]. Diagnostic accuracy is critical, as it will significantly affect parental counseling and decision-making regarding continuation of the current pregnancy, as well as options for prenatal or preimplantation genetic diagnosis in future pregnancies. After birth, postnatal radiographs, autopsy (in lethal cases), and molecular testing are crucial for making an accurate diagnosis [3,7,8].

This topic will discuss lethal skeletal dysplasias that present prenatally. The majority of skeletal dysplasias will present postnatally with obvious clinical manifestations. Postnatal evaluation, clinical findings, and diagnosis of skeletal dysplasias are reviewed separately. (See "Skeletal dysplasias: Approach to evaluation" and "Skeletal dysplasias: Specific disorders".)


Although each type of skeletal dysplasia is rare, the overall birth prevalence of skeletal dysplasias is estimated to be 2.4 per 10,000 births [1,9,10]. The prevalence during pregnancy appears to be slightly higher at 7.5 per 10,000 ultrasound-screened pregnancies [11].


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