Merosin-deficient muscular dystrophy, a type of congenital MD, might be diagnosed before birth using immunohistochemistry, an easy and quick lab test that looks for specific markers in cells from a mother’s placenta, according to a small study of pregnant women whose children are at risk for this disease.
A misdiagnosis, however, is possible if the test lacks an “index case with complete merosin deficiency,” the researchers said.
The study, “Prenatal Diagnosis of Merosin-Deficient Muscular Dystrophy,” was published in Fetal and Pediatric Pathology.
Muscular dystrophy (MD) covers a group of disorders characterized by varying degrees of muscle weakness. One congenital type, merosin-deficient muscular dystrophy, is caused by the lack of laminin-alpha 2, known as merosin, which is one of the proteins required to build muscle fibers. This deficiency stems from mutations in the LAMA2 gene. The disease is inherited in an autosomal recessive manner, meaning both parents need to be mutation carriers, and further pregnancies carry a 1 in 4 risk of a child with merosin-deficient MD.
Merosin-negative children have a wide array of symptoms that can be severe and life-threatening, including generalized muscle weakness, joint contractures (limitations on full range of motion), neurologic problems, and scoliosis. Their severity and the disease’s course are both highly variable, and seem to be directly related to merosin levels in muscle fibers.
For this reason, merosin-negative MD is usually diagnosed via immunohistochemistry — a lab test that allows for the visualization of merosin inside muscle fibers — coupled with genetic screenings to identify known mutations.
Since merosin is also found in trophoblast cells in the mother’s placenta, researchers in Turkey investigated whether the immunohistochemistry technique might be a tool for prenatal diagnosis of merosin-deficient MD in an unborn child.
“The prenatal diagnosis of this disease is critical for family counseling and pregnancy management,” the researchers said.
Their retrospective study looked at pregnancies in 12 women from eight families; each had previously given birth to a child with merosin-negative MD. Researchers examined a sample of cells collected from the mother’s placenta between the 11th and 13th week of pregnancy by chorionic villus sampling (CVS), a standard prenatal test to assess genetic problems in a fetus.
Immunohistochemical analyses of placenta cells found two of the 12 pregnancies were merosin-negative, meaning that no staining, or visualization, was evident. Both were terminated with informed parental consent at the 14th week of gestation. An autopsy was not performed on these fetuses at their parents’ request, but a “gross examination” found “none of the manifestations related to the disease,” the researchers said.
Ten pregnancies showed merosin-positive results and eight ended with babies born healthy (two families were lost in follow-up), with no reports of false-positive test results. In all cases, fetal ultrasonographies were normal.
“Confirmation of the merosin-negative CVS results by muscle tissue analysis was not possible in our study due to the parental refusal of post-mortem fetal examinations,” the researchers said. “Merosin-positive patients were followed up for different durations, and none had symptoms related to muscular dystrophy.”
These findings, they concluded, support immunohistochemistry as a specific and fast way — one that “may be evaluated as reliable” — of diagnosing merosin-negative MD before birth “to ensure appropriate patient management.”
But “the possibility of partial merosin deficiency must also be kept in mind to avoid prenatal misdiagnosis,” the research team added, noting that “immunohistochemical studies alone may be used for prenatal diagnosis … in the existence of an index case with complete merosin deficiency.”