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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 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, etc) or intrinsic causes (single gene disorders with autosomal dominant, recessive, or X-linked modes of inheritance; imprinting errors; chromosome abnormalities) [1]. In view of the large number of skeletal dysplasias (over 456 known types), a classification system was created that categorizes genetic bone disorders into 40 major groups by their cardinal features (eg, radiological findings, molecular etiology, inheritance) [2,3].

Prenatal diagnosis is based primarily upon fetal ultrasound findings, but magnetic resonance imaging (MRI), computed tomography (CT), radiography, and in some cases, molecular analysis, may be used to support the presumptive diagnosis. Skeletal dysplasias can usually be identified by prenatal ultrasound examination because most of the skeleton begins to ossify early in development (the clavicle, mandible, ileum, scapula, and long bones ossify by 12 weeks of gestation; the metacarpals and metatarsals are ossified by 12 to 16 weeks; the talus and calcaneus ossify at weeks 22 to 24; but the carpal bones ossify after birth; epiphyseal ossification centers are seen on radiographs at approximately 20 weeks of gestation) [4].

The lethal group of skeletal dysplasias typically have an earlier onset with more severe phenotypic features than the non-lethal group, thus lethal skeletal dysplasia are potentially more amenable to early diagnosis [5]. Diagnostic accuracy is critical, as it will significantly affect parental counseling and decision making regarding continuation of the current pregnancy, as well as their options for prenatal diagnosis in their future pregnancies. In retrospective studies, experienced ultrasonographers made accurate prenatal diagnosis of lethal skeletal dysplasias in 81 to 100 percent of cases versus 31 to 78 percent of all cases of skeletal dysplasia [5-8]. The most challenging diagnoses are the skeletal dysplasia with variable phenotypic expression, which are not always lethal.

After birth, postnatal radiographs, autopsy (in lethal cases), and molecular testing are crucial for making an accurate diagnosis [3,9,10].


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 [11,12]. The prevalence during pregnancy appears to be slightly higher at 7.5 per 10,000 ultrasound screened pregnancies [13].


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Literature review current through: Sep 2016. | This topic last updated: Sep 8, 2015.
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