Elsevier

Clinics in Perinatology

Volume 27, Issue 4, 1 December 2000, Pages 979-1005
Clinics in Perinatology

SKELETAL ANOMALIES

https://doi.org/10.1016/S0095-5108(05)70060-9Get rights and content

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Take a Detailed History

This should include a family history including ethnicity, any history of consanguinity, the heights of family members, any history of prenatal or perinatal deaths, and the etiologies. In addition, the patient should be questioned about a history of diabetes mellitus; varicella during the pregnancy; and teratogen exposure including drugs, radiation, and chemicals. Certain skeletal dysplasias occur at a higher incidence in select ethnic groups. For example, chondroectodermal dysplasia (Ellis-van

MOLECULAR GENETIC DIAGNOSIS OF SKELETAL DYSPLASIAS

A number of genes and mutations that cause chondrodysplasias have been identified. The mutations affect the proliferation and differentiation of growth plate chondrocytes and the coincident genesis and modulation of cartilage matrix that serves as a template for bone formation and gives rise to the articular surfaces of joints. Fortunately, from a diagnostic perspective it seems that over half of all humans with chondrodysplasias have mutations at either the COL2A1 or FGFR3 loci.50

HETEROZYGOUS ACHONDROPLASIA

Heterozygous achondroplasia is the most common chondrodysplasia. This nonlethal condition occurs with a frequency of approximately 1 in 15,000 births. Affected individuals have rhizomelic shortening of the limbs, megalocephaly with frontal bossing, mid-face hypoplasia, and short trident hands (Fig. 2). Intelligence is usually normal.58 There is an increased risk of mortality during the first 5 years, and especially during the first year, from sudden death, most likely secondary to compression

LETHAL OSTEOCHONDRODYSPLASIAS

Since thanatophoric dysplasia was described in 1967,71 many lethal chondrodysplasias have been delineated. Spranger and Maroteaux109 have published a nosology of lethal osteochondrodysplasias that have been grouped according to phenotype. A list of the more common lethal osteochondrodysplasias along with inheritance and genetic mutations, when known, is found in Table 1. Using ultrasound, it is now possible to identify nearly all lethal osteochondrodysplasias prenatally.88 Some of the lethal

Chondroectodermal Dysplasia (Ellis-van Creveld Syndrome)

Chondroectodermal dysplasia is an autosomal recessive osteochondrodystrophy that was first described by Ellis and van Creveld29 in 1940. It is characterized by acromesomelia, postaxial polydactyly, ectodermal defects, and congenital heart disease. All affected individuals have polydactyly of the hands and in 10% of cases the feet are also affected (Fig. 12).91 Approximately half of affected individuals have congenital heart disease, the most common defect being atrial septal defects, often with

SUMMARY

It is possible to identify many types of skeletal dysplasias and conditions involving limb deformities prenatally using ultrasound. It is likely that in the future, with the advancing technology and discoveries in molecular genetics, specific mutation analysis will become available for many of these conditions. This will make first trimester diagnosis an option in many cases.

Because of the complex nature of many of these cases, it may be helpful to use a multidisciplinary approach involving a

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