Journal List > Korean J Obstet Gynecol > v.53(6) > 1006423

Kim, Kim, Kim, You, Oh, Park, Lee, Kim, Chun, and Park: Prenatal detection of skeletal dysplasia using ultrasound and molecular diagnosis

Abstract

Objective

To determine the accuracy and usefulness of prenatal ultrasonographic and molecular genetic diagnosis in detection of skeletal dysplasia.

Methods

This study was based upon data of the 17 cases of skeletal dysplasia diagnosed by prenatal ultrasound and 7 cases by molecular diagnosis performed among the 17 cases and the 2 cases who has familial skeletal dysplasia by molecular diagnosis during the first trimester at Ewha and Eulji University from March 1998 to August 2005. A final diagnosis was sought on the basis of radiographic studies, molecular testing, or both.

Results

The mean gestational age at diagnosis was 24.9 weeks (range, 17 to 35 weeks). Nine cases were diagnosed before 24 weeks. A final diagnosis was obtained in 16 cases (94.1%). There was 1 false-positive diagnosis. The antenatal diagnosis was correct in 14 cases (82.4%). The 8 cases were prenatally confirmed and 1 case was postpartum confirmed using molecular genetic testing and accurate antenatal diagnosis and prediction was done. We were able to rule out skeletal dysplasia through chorionic villus sampling during the first trimester in the 2 cases with the family history with skeletal dysplasia.

Conclusion

Prenatal diagnosis of skeletal dysplasia can be a considerable diagnostic challenge. However, skeletal dysplasia is correctly diagnosed on the basis of prenatal meticulous ultrasound and antenatal prediction of lethality was highly accurate. Using prenatal molecular diagnosis, skeletal dysplasia can be diagnosed at first trimester of pregnancy and nonlethal skeletal dysplasia can be confirmed when prenatal ultrasound was nonspecific.

Figures and Tables

Figure 1
Infantograms of skeletal dysplasia. (A) Jarco-Levin syndrome. There are kyphoscoliosis and dyssegmentation of thoracic spines, agenesis of right upper ribs and fan-like appearance of right lower ribs. (B) Camptomelic dysplasia. There are bowing of both femur and hypoplastic scapula. (C) Achondroplasia. The long bones are rhizomelic shortening and mild bowing. Head is enlarged. (D) Osteogenesis imperfecta. There are severe micromelia, multiple fracture, brittle bone. (E) Thanatophoric dysplasia, type 1. Marked limb shortening and characteristic bowed telephone receiver femur are demonstrated.
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Figure 2
Mitten hand of Apert syndrome in postnatal photograpy.
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Figure 3
Molecular studies of the osteogenesis imperfecta mother and the normal fetus. (A) Osteogenesis imperfecta mother : Col 1A2:G982A heterozygote (red arrow), (B) Normal baby
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Table 1
Genes that can be screened or diagnosed in uterus
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For a more detailed list of biochemical and molecular tests available for the diagnosis of skeletal dysplasia, see the University of Washington-sponsored WorldWideWeb page GeneTests (http://www.genetests.org).

COL1A1: Collagen Type1 Alpah 1, COL1A2: collagen type 1 alpha 2, COL2A1: collagen type 2 alpha 1, COL9A1: collagen type IX alpha 1, COL9A2: collagen type IX alpha 2, COL9A3: collagen type IX alpha 3, COMP: cartilage oligomeric matrix protein gene, EVC: Ellis-van Creveld, DTDST (SLC26A2): diastrophic dysplasia sulfate transporter (solute carrier family 26[sulfate transporter] member 2), MATN3: matrilin 3, RUNX2: runt-related transcription factor 2, FGFR: fibroblast growth factor receptor, SADDAN: severe achondroplasia with developmental delay and acanthosis nigricans.

Table 2
Sonographic abnormalities
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CC: cardiac circumference, TC: thoracic circumference.

Table 3
Prenatal diagnosis and final diagnosis for each case
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*Molecular study case.

Table 4
Outcome of pregnancy
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TOP: termination of pregnancy.

Table 5
Summary of molecular study in diagnosis of skeletal dysplasia
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FGFR: fibroblast growth factor receptor, COL1: type I collagen.

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