Epidemiological aspects of Mendelian syndromes in a Spanish population sample: II. Autosomal recessive malformation syndromes

Abstract

From April, 1976, to December, 1988, the Spanish Collaborative Study of Congenital Malformations (ECEMC) monitored a total population of 710,815 liveborn infants in 16 of 17 Spanish Regions and identified 14,439 (2.0%) with congenital defects. Among the malformed children, we identified 73 with well recognized autosomal recessive syndromes, for an overall prevalence rate of 10.3 per 100,000 livebirths and a total carrier frequency of 1/49. Considering the Spanish Regions (Comunidades Autónomas), we analyzed the geographical distributions of these syndromes that were homogeneous. We studied the place of birth of the grandparents to determine the distribution of the gene as well as the gene flow.

Descriptive epidemiology of selected heritable birth defects in Texas

“…Infantile PKD is an autosomal recessive malformation syndrome caused by mutations in PKHD1 . PKD is one of the more common of autosomal recessive congenital malformation syndromes (Martinez‐Frias et al,1991). The birth prevalence in Texas was within the reported estimates ranging from 1.41/100,000 (Martinez‐Frias et al,1991) to 12.6/100,000 (Kääriäinen,1987).…”

“…PKD is one of the more common of autosomal recessive congenital malformation syndromes (Martinez‐Frias et al,1991). The birth prevalence in Texas was within the reported estimates ranging from 1.41/100,000 (Martinez‐Frias et al,1991) to 12.6/100,000 (Kääriäinen,1987). Our findings for the infant gender rates were consistent with the literature's gender ratio of 1:1 (Kääriäinen,1987).…”

The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect

“…Based on the population incidence of sporadic cases (10,(18)(19)(20)38), both conditions have exceptionally high mutation frequencies (1͞15,000-1͞70,000) when compared with what is known about other single nucleotide substitutions at CpG sites (40). This high rate led to the original idea of a DNA mutation hot spot (14,15,37,41).…”

“…Second, all sporadic achondroplasia cases have been found to inherit the G1138A mutation from their father (17). Third, recent data on the population incidence of sporadic achondroplasia (10,(18)(19)(20) predict the average frequency of sperm carrying the mutation in normal individuals will be in a range detectable by modern molecular methods (1͞15,000 to 1͞70,000). Our studies on sperm DNA from men of different ages suggest that the observed increase in G1138A mutation frequency cannot satisfactorily explain the exponential increase in sporadic achondroplasia cases with paternal age.…”

Do parents and grandparents of patients with achondroplasia have a higher cancer risk?

“…Our hypothesis of a mutator gene may fit well with these premutagenic lesions. Moreover achondroplasia has exceptionally high mutation frequencies (1/15,000–1/70,000) [Camera and Mastroiacovo, 1988; Stoll et al, 1989; Martinez Frias et al, 1991; Orioli et al, 1995; Wilkie et al, 1995] when compared with the mutation frequencies of other single nucleotides substitutions at CpG sites [Nachman and Crowell, 2000].…”