Cleft-Twin Sets in Finland 1948–1987

Abstract

Extensive review of the literature since 1884 on cleft-twin sets yielded 364 cleft-twin sets. Of these, 118 were monozygotic (MZ) and 246 dizygotic (DZ) sets. In addition, Danish material on cleft twins, like our Finnish material, reflects the total number of clefts and cleft twins on a well-defined population during a well-defined time interval. Both sets of material also contain slightly over 100 pairs of twins. The Danish material and the literature review were compared to the Finnish material. The hospital records of all Finnish patients with operated clefts who were born between 1948 and 1987 were reviewed. Information was gathered regarding each patient, his parents, the pregnancy, and his twin or triplet siblings and other siblings. This search produced 105 sets of twins and three sets of triplets with clefts, 15 sets of twins being concordant regarding clefting. This resulted in a total of 120 cleft siblings, and the corrected cleft incidence of 1.72 promille, close to the overall cleft incidence rate in Finland between 1948 and 1975. Twinning was found to be associated neither with an increased nor with a decreased risk of clefting, and clefting could not be seen to increase twinning. Zygosity could be verified in 88 sets of twins; the total number of MZ sets was 17, and of DZ was 71, a 19% MZ rate. Although a higher incidence of clefting in MZ-twin sets has been proposed, no such higher or lower incidence could be found in our material. Recognized syndromes were found in 15 sets (14%), slightly higher than found in a large Finnish study on cleft probands (8.4%). Of these, three sets were monozygotic (MZ), all of them cleft palate (CP) and male sets, whereas eight sets were dizygotic (DZ). All 15 sets were CP only, with no one set with cleft lip and palate [CL(P)]. In our total Finnish-twin material of 105 sets, we found the CL(P)/CP ratio to be 39/66 (37%/63%). In all of the 120 affected siblings, the ratio was 35%/65%. The very high rate of 63% of CP twins is about two to three times higher than that reported in the literature of 364 sets where the CP ratio is 23%; compared to the Danish material with a CP ratio of 17%, it is almost four-fold. The overall CP rate in all clefts (not restricted to twins)in Finland compared to the rate In our neighboring Scandinavian countries was very much in line with this very big difference seen in the CP rate In our twin material. The CL(P) Incidence in our Finnish material is 0.61 promille and the CP incidence 1.11 promille. For MZCL(P), the incidence was 0.38 promilie; for MZCP, 0.91 promille; for DZCL(P), 0.52 promille, and for DZCP, 0.99 promille. Compared to the Danish figures, both the MZCP and DZCP incidence figures are nearly four-fold, with the MZCL(P) somewhat lower, and DZCL(P) less than half that number. The sex distribution of all cleft patients in our material was 44% male/56% female. Both in the Danish material and in the literature, it was the reverse. This difference is probably due mostly to the higher ratio of CP in the Finnish material. The CP group has a higher proportion of females in all these materials. The concordance (C) of the whole Finnish-twin material is 14%, compared to 16.5% reported in the literature and 8% for the Danish twins. The concordance for CL(P) In our material is many times lower (2.6%) than in the literature (17.1%) and In the Danish material (8%). In the Finnish twins, the C for CP is higher (17%) than that for the Danish (6%) and for the literature cleft-twin populations (14.3%). This is also true for the MZ and DZ subgroups. The heritability index (H) in CL(P) is lower for the Finns (17%) than for the Danish (45%) and for the literature materials (43%), and higher for CP (Finns 49%, Danish 33%, literature 36%). All of these data strongly suggest the quite different genetic behavior of both CL(P) and CP in Finland, with a much lower genetic component in the CL(P) and a higher In the CP.

Recurrence risk for offspring of twins discordant for oral cleft: A population‐based cohort study of the Danish 1936–2004 cleft twin cohort

“…A direct comparison of the OC occurrence among twins and singletons would be more suited to answer that question. Previous results have been ambiguous, but the majority found similar OC prevalence for twins and singletons [Christensen et al, 1993a; Christensen et al, 1993b; Christensen et al, 1996a; Mitchell et al, 1997; Nordstrom et al, 1996; Robert et al, 1996]. …”

1q32-q41 microdeletion with reference to van der Woude syndrome and allied clefting entities

“…Indeed, it had been estimated that only ∼2% of the "patients with clefts" had LLP (or their equivalent) from a large Finnish population sample [Rintala and Ranta, 1981]. It was presumed that most of these patients had vWS, which was estimated to have an incidence of ∼3: 100,000 [Rintala and Ranta, 1981], also in agreement with a corrected combined incidence of ∼1.5‰ for CL/P in this population [Nordström et al, 1996]. Because ∼60% of CL/P patients have associated anomalies, half of whom as the result of a recognizable syndrome, sequence, or association [Shprintzen et al, 1985], it was reasonable to think that as many as ∼1.3% of NSCL/P cases without LLP would have been related to a mutation of the vWS gene.…”

Addressing the challenges of cleft lip and palate research in India

“…[23] The concordance rates for CL/P are higher in monozygotic twin pairs than in dizygotic pairs. [24][25][26] The familial clustering and concordance in twins of CL/P and CP has been observed to be specific for each defect, and therefore the defects are considered to be etiologically heterogeneous. [26][27][28][29] There exists a male preponderance in CL/P predominance of left-sided clefting.…”

“…[24][25][26] The familial clustering and concordance in twins of CL/P and CP has been observed to be specific for each defect, and therefore the defects are considered to be etiologically heterogeneous. [26][27][28][29] There exists a male preponderance in CL/P predominance of left-sided clefting. [30] In an attempt to determine which genes are involved, genetic linkage studies have been conducted suggesting a variety of loci, including regions on chromosomes 1, 2, 4, 6, 9, 14, 17, and 19.…”