Differences between predicted and established diagnoses of Smith-Lemli-Opitz syndrome in the Polish population: underdiagnosis or loss of affected fetuses?

Smith-Lemli-Opitz syndrome (SLOS) is a metabolic disorder in which an error in cholesterol biosynthesis results in congenital anomalies/mental deficits. The results of our previous newborn screening, based on the carrier frequency of the two most common SLOS-causing mutations in Poland (p.W151X and p.V326L), would make SLOS one of the most frequent recessive disorders in our country (with an incidence of 1:2,300 – 1:3,937). This prompted us to carry out a 3-year (2006–2008) national surveillance program in which about 2,000 physicians were asked to identify potential SLOS patients pre- and postnatally based on clinical identification forms. The incidence of SLOS in Poland was estimated to be from 1:60,941 to 1:105,395 (1: 83,168 ± 22,227) live births, and its 3-year prevalence 1:866,273 ± 16,242. The mean carrier frequency was calculated to be from 1:123 to 1:165. The notable discrepancy between our previous carrier newborn screening and these prospective data may result from reduced fertility in SLOS carriers, intrauterine death of affected fetuses, or underdiagnosis in postnatal life. Since we did not notice significant data supporting the first two aspects, our study may support the suggestion that screening for the most frequent DHCR7 alleles does not reflect the true disease rates in the Polish population. Hence, further studies in which maternal urinary steroids (7-dehydroestriol/estriol and 8-dehydropregnanetriol/pregnanetriol ratios) would serve as screening markers in early pregnancies may be justified.