PRENATAL PREDICTION IN FAMILIES WITH AUTOSOMAL RECESSIVE PROXIMAL SPINAL MUSCULAR-ATROPHY (5Q11.2-Q13.3) - MOLECULAR-GENETICS AND CLINICAL-EXPERIENCE IN 109 CASES

Prenatal prediction in families at risk for autosomal recessive proxim al spinal muscular atrophy (SMA) mainly of type I is often requested d ue to the high incidence and the fatal outcome of the disease. So far, only indirect genotype analysis can be performed in SMA families, sin ce the gene has not yet been identified. We present our experience of 109 prenatal diagnoses obtained in 91 families by use of single- and m ulti-locus polymorphic microsatellites of the region 5q11.2-q13.3. The marker combinations and specific features of the closest microsatelli tes are described in detail. From 137 requests for prenatal prediction of SMA between October 1991 and August 1994, 28 families were exclude d, mostly because the clinical diagnosis was uncertain or doubtful. Ot hers had to be classified as 'SMA-variants' or showed autosomal domina nt transmission of SMA. Of the 109 prenatal diagnoses performed, 29 fe tuses were diagnosed to be at high risk (>99 per cent) of developing t he disease, while in seven additional pregnancies no exact prediction could be made due to a recombination event in one parental haplotype. Altogether, recombinations between closely flanking markers were obser ved in 14 cases. In 35 cases, the parents decided to terminate the pre gnancy. Of the remaining pregnancies, 32 could be followed beyond term . All infants were reported to develop normally without signs of SMA. Two children were born with transverse reduction defects of one hand, which was most likely related to early chorionic villus sampling at 9 and 10 weeks' gestation. No further abnormalities could be detected. T he limits of indirect genotype analysis and the problems of diagnostic accuracy and heterogeneity of proximal SMA are discussed.