Journal ofMedical Genetics, 1980, 17, 127-132

An epidemiological study of facial clefting
in Manitoba
JOAN WELCH AND ALASDAIR G W HUNTER

From the Department ofPaediatrics, Children's Hospital of Winnipeg, and University of Manitoba,
Winnipeg, Manitoba, Canada

SUMMARY The results of an epidemiological survey of facial clefting in the province of Manitoba
which covered the years 1964 to 1977, inclusive, are reported. The mean annual incidence of total
facial clefts was 2 in 1000 births; the incidence of cleft lip ± cleft palate (CLP), and of cleft palate
(CP), unassociated with a syndrome or two or more major malformations, was 1 05 in 1000 and
0.46 in 1000, respectively. Mennonite infants were over-represented in the CLP group and
Amerindian infants in both the CLP and CP groups. These ethnic groups also had more familial cases
and showed higher average coefficients of inbreeding. Recurrence rates among sibs were found to be
influenced by the presence or absence of additional affected relatives and by the presence of mal-
formations in the proband. It is possible that these latter two variables may not be independent.

This study was undertaken in order to assess the
incidence of facial clefting in Manitoba, to search
for possible associations of clefting with demo-
graphic variables, and to determine the recurrence
rates of facial clefting in families ascertained through
an affected child. Of particular interest was how
the occurrence of affected second and third degree
relatives of the proband, and the presence or absence
of additional malformations, would influence
recurrence rates.

Methods

Children born with facial clefts in the province of
Manitoba from 1 January 1964 to 31 December 1977,
inclusive, were ascertained through a direct search
of the records of all Winnipeg hospitals, the Pro-
vincial Congenital Anomalies Registry, dental
records of the Orthodontic Department of the
University of Manitoba and of private Manitoba
orthodontists, and through inquiries to other
provincial hospitals and nursing stations.

Surgical repair of facial clefts in Manitoba has
been limited to Winnipeg hospitals throughout the
study period and there are no neighbouring extra-
provincial centres that draw patients away from the
province for surgery. Treatment of facial clefts is
the rule in surviving infants and ascertainment of
this group is likely to be close to 100 %. Some infants
who were stillborn or died in the perinatal period
may have been missed.
Received for publication 6 June 1979

127

An attempt was made to contact the families of
affected children in order to complete a questionnaire
and to supplement information contained in the
various medical records. Approximately half the
families were contacted; appropriate adjustments
were made for missing data. The data were coded for
analysis by computer.
Each case was assigned first to either the cleft

palate without cleft lip (CP), or to the lateral cleft
lip with or without cleft palate (CLP) group.'
Patients with a recognised syndrome or multiple
congenital anomalies (MCA) (defined here as two or
more major malformations in addition to the cleft)
were considered separately. In addition, for some
aspects of the study, the CP and CLP patients were
further subdivided according to the type ofadditional
malformations present: none, one minor, more than
one minor, one major, one major plus minor.

Results and discussion

A total of 507 children with facial clefts from 492
Manitoba families was ascertained. In the event that
more than one affected child was born into a family
during the study period, the oldest child was
normally considered the index case or proband. The
proband of these multiply ascertained families is
marked with an asterisk in the appendix.* All 507
cases were used in such calculations as incidence and

*The details of each case are shown in an appendix,
available from the authors on request.

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Joan Welch and Alasdair G WHunter

sex ratios, whereas each family was counted only
once when considering associated variables that
would have been biased by repeated inclusion of the
same data.
There was no evidence of any secular change in

incidence over the study period and the average
annual incidence of 2-00 per 1000 births is in the
middle range of values reported from previous
studies.2 3 In 108 cases (21 3%) from 105 families
the cleft was part of a recognised syndrome or
malformation complex. The remaining 399 cases
consisted of 264 cases of CLP from 258 families,
124 cases of CP from 121 families, and 11 cases
lacking information as to cleft type or the presence
or absence of associated malformations or both. The
mean annual incidence of CLP was 1-04 in 1000
births and of CP was 0'46 in 1000 births; these
figures are comparable to previous reports.1 2

In table 1 the CLP and CP patients are subdivided
according to sex, and the location and severity of
defect. A significant male excess in CLP was con-
firmed (pr<c005),L 4 and more severe defects
(CL + P and clefts of both the hard and soft palate)
were more frequent than either isolated CL or cleft

TABLE 1 Sex ratio, location, and severity offacial
clefting
Cleft lip and palate (264) Cleft palate (124)

Total Frequency Total Frequency

Male 159 59.8* Male 59 47-6
Female 104 39-4 Female 65 52.4
Unknown 1 0*8
Cleft lip only 67 25*3 Secondary
Cleft lip and palate 88 71-0

palate 197 74.7 Soft palate
Bilateral 46 17.4 only 23 18-5
Right unilateral 78 29.5 Submucous 11 8-9
Left unilateral 95 36.0 Unclassified 2 1.6
Unclassified 45 17.0

*p <0*005.

of the soft palate. Previous studies have found an
excess of left over right unilateral CLP cases1 5-7;
although we observed this trend the difference was
not significant.
There was an excess of female cases of CP but this

did not reach the level of significance noted in
previous studies.6 8 Emmanuel8 found that the
deviation from 1:1 in the sex ratio usually observed
for CLP and CP patients was not seen in patients
with associated major malformations. The male
excess in CLP was maintained for all subgroups in
our sample except those with MCAs and syndromes;
the sex ratio did not differ from 1:1 in any of the CP
subgroups.
Even after cases with recognised syndromes or

multiple anomalies had been removed, 15 4% of
CLP and 16 0 % of CP patients had at least one
major or minor anomaly or both. Seven of 252
(2 78%) CLP cases and four of 118 (3 39%) CP
cases had congenital heart defects (mostly ventricular
septal defects). This incidence is significantly greater
than that in the general population9 for the CLP
cases (p<0 025), but does not attain significance for
the CP patients where the numbers are smaller.
Mean paternal age was 29 7 years for the CLP

group, 30 0 years for the CP group, and 26 5 years
for the general population.10 Mean maternal age was
26 2 years for both the CLP and CP groups,
compared to a population mean of 23-1 years.10
Mean parity was 2 8 for the CLP and 2 7 for the CP
mothers, compared to 2-4 among the general
population. Parental age and parity appear to be
increased, but the nature of the control data did not
allow formal significance testing. Several previous
studies have suggested a possible parental age
effect.1 11

Racial and ethnic variation in the incidence of
facial clefting is well established.' 8 The population

TABLE 2 Distribution of cases by ethnic group
Ethnic group Proportion of CL(P) CP

population.
Mean of male and No of cases No of cases
female

Observed Expected Observed Expected

British Isles 0.415 85 89-5 38 39
French 0.09 16 19-5 4 8-5
German/Dutch

(Mennonite) 0.16 47 34-5* 13 15
Italian 0.01 1 2 2 1
Slavic, Slovak 0.165 28 35.5 15 15-5
Native Indian 0.04 32 8.5** 18 4**
Jewish 0*02 2 4 1 2
Asian 0*007 2 1 0 0.5
Negro 0.001 1 0 0 0
Scandinavian 0*035 2 7-5 2 3
Other 0*03 3 6- 5 2 3
Total 219 95

*Statistically significant difference. **Highly significant.

128

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An epidemiological study offacial clefting in Manitoba

of Manitoba is ethnically diverse, and the observed
and expected numbers of clefts based on the propor-
tion that each ethnic group represents in the total
Manitoba population are shown in table 2. Tables
based on maternal and paternal origin were so
similar that they have been combined. There was a
significant excess of Mennonite infants with CLP
and a highly significant excess of both CLP and CP
among Amerindian infants. These ethnic variations
may represent a difference in the incidence of
clefting or they may simply reflect differences in
fertility. Unfortunately no ethnic specific fertility
data are available for the general provincial popula-
tion. However, it is difficult to attribute a specific
increase in CLP among the Mennonites to a
difference in fertility. Moreover, the magnitude of the
excess is partially hidden, as the control group
contains all persons of German and Dutch origin
whereas the clefting population has been noted to be
heavily weighted towards Mennonites (considered
German or Dutch by Statistics Canada). The
increased incidence among Amerindians is of such a
magnitude as to suggest that increased fertility is not
the sole explanation. Lowry and Renwick12 and
Emmanuel et a!8 have reported an excess of facial
clefting among Amerindians. This ethnic distribution
was reflected in a significant excess of CLP in
Eastern and Central Manitoba, where many
Mennonite communities are located, and of CP in
Northern Manitoba, where a larger proportion of the
population is native.

Twenty-eight of 189 (14 8%) CLP cases and 18 of
82 (22-0%; p<0 05) CP cases were illegitimate,
compared to a 12 8 % rate for the general population
in the middle year of the study.10 Fourteen of the
18 illegitimate births in the CP group were
Amerindian and a higher frequency of both clefting
and illegitimacy among the native group accounted
for the excess of illegitimate births in the CP cases.
Although the numbers were small, there was a

3- and 4- 5-fold excess of consanguinity (third
cousins or closer) between the parents of the CLP
and CP patients, respectively, over that of 0-8%
recorded for a local population (Hamerton et al,
unpublished data). Most of the relatively limited data
available do not support an association of con-
sanguinity with clefting,l although a possible effect in
cleft lip was noted by Woolf5 and in CP by Fujino
et al.13 Sixteen of 138 (11.6%) CLP mothers and
12 of 63 (19-0%) of CP mothers reported first
trimester illnesses. The difference between the two
groups is statistically significant (p<0 05). Retro-
spective maternal memory bias would be expected to
be greater among mothers of the more visible and
emotionally overlaid CLP group and the frequency
of first trimester illnesses reported is considerably

129

greater than that reported by Fraser,' who found no
significant differences between normal controls and
cleft palate mothers.

Previous stillbirths were significantly more
frequent in CLP mothers (10 in 148; 6 8%) than in
the general population of Manitoba (2 7 %)
(Hamerton et al, unpublished data; p<0 01),
whereas the frequency in CP mothers (3 in 75; 4 0%)
was not significantly different from the expected rate.
A past history of spontaneous abortion occurred
with the same frequency among CLP (20 7%), CP
(20 3 %), and women in the general population
(17- 1%) (Hamerton et al, unpublished data). An
unexpected finding was that 7 6% of CLP mothers
and 10% of CP mothers had given birth to an
additional child with a different malformation.

Variables that did not appear to have any relation-
ship to the occurrence of clefting included birth-
weight, gestational age, season of birth, twin births,
maternal smoking during pregnancy, parental
education, and occupation.

Family data

The patients in the MCA and syndrome groups
represent a broad range of known and unknown
aetiologies (included in appendix). As expected, a
number of clefting syndromes are represented and
some show a positive family history. On the other
hand there are several syndromes (for example
Down's, Goldenhar's, Marfanoid hypermobility)
where cleft palate is a less frequent component of
the syndrome, and it is perhaps significant that a
positive family history of isolated clefting (that is,
without the syndrome) is common in these patients.
This supports the concept that even in syndromes of
known aetiology, the expression of a particular
malformation may be influenced by the genetic
background of the individual patient.
The frequency of clefting among first and second

degree relatives of CLP and CP cases is given in
table 3. CLP occurred 33 times more frequently
among first degree relatives (sibs), and 13 times more
frequently among second degree relatives, than in the
general population; the figures for CP were 119 and
21 - 5 times, respectively. This increased rate in
relatives with a rapid fall-off in incidence with degree
of relationship is compatible with polygenic inheri-
tance,L 5 6 but we could not assess the rates in third
degree relatives. The lower frequency of clefting in
parents as compared to sibs of affected children is
perhaps explained by a decreased genetic fitness
among cleft patients. Similar data were reported by
Woolf5 and Bear.6

Table 4 shows that the recurrence rate in sibs is
influenced by the presence or absence of other

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130

TABLE 3 Clefts in first and second degree relatives of
probands

First degree relatives Second degree
relatives

Sibs Fathers Mothers (Grandparents,
aunts, uncles,
nieces, nephews)

CLP
Total No 350 179 185 1187
No affected 12 5 2 16
Frequency

affected 3-42% 2-8% 1.1% 1-35%
Parents = 2 0%

CP
Total No 146 69 83 504
No affected 8 1 3 5
Frequency

affected 5.48% 1.44% 3*6% 0.99%
Parents = 2.52%

TABLE 4 Family history and sib recurrence rate
Family history CLP CP

Total Sibs Total Sibs
sibs affected sibs affected

None 267 6 115 2
(2 *25 Y.) (1.74%)

Cleft in parent 8 0 2 1
(50*0%)

Cleft in 2nd degree 25 3 16 3
relative (12 .0%/Y) (18*8%/)

Cleft in 3rd degree 52 3 37 2
relative (5.76%) (5-41%)

affected family members. Sibs from CLP and CP
families where the index case is the sole affected
member are at significantly lower risk than sibs from
families where a second or third degree relative is
affected. Thus, the genetic component of both CLP
and CP appears to be high and the heritability,
based on sib data, was calculated to be 75 % and

Joan Welch and Alasdair G WHunter

77 %, respectively.14 There was the same increased
number of Mennonites among the familial CLP and
of Amerindians among the familial CLP and CP
groups as was seen in the total groups. Parental age
data and sex ratio showed no significant difference
between familial and sporadic cases for either CLP or
CP.
There were few sibs born to families where a

parent was also affected and this was apparently
because of restriction of further reproduction once a
child with a cleft was born. The mean sibship size for
CLP and CP families in this study was 3 4 and 3 6,
respectively, but in CLP and CP families where a
parent was also affected the mean number of sibs was
I * 8 and 0 7, respectively.
Woolf et al'5 suggested that most polygenic cases

of CLP lack associated malformations and that cases
of CLP with associated malformation either result
from rare mutant genes, or from some teratological
agent, or from chromosomal aberrations. In a study
of CLP in 19715 he found that the sib recurrence risk
in cases where the index case had an associated
malformation was significantly lower than in cases
where there were no additional defects. Bear6 found
no variation dependent upon associated malforma-
tions. Although the numbers are small our frequency
of affected relatives in the CLP and CP groups was
consistently greater when the proband had an
associated major or minor malformation or both
(table 5). The affected relatives lacked the associated
malformation. The excess of minor anomalies in
the familial group could be considered equivalent to
the fluctuating dermatoglyphic asymmetry noted in
sibs and parents ofCLP cases by Woolfand Gianas.16
The authors considered this as evidence of polygenic
inheritance of CLP.

Thus, recurrence rates among sibs of index cases

TABLE 5 Frequency ofaffected relatives as a function ofadditional major or minor malformation in proband
Additional malformations No of cases No of sibs No of sibs Parents No of 2nd No of2nd No of3rd

affected affected degree degree relatives degree relatives
relatives affected affected

CLP
Pure 221 308 10 (3-2%) 7 (1-6%) 992 16 (1-6%) 47
1 minor 16 20 2 (10%) 0 137 0 7
>2 minor 3 6 0 0 15 0 2
1imajor 16 15 0 0 28 0 0
1 major + 1 minor 2 1 0 0 15 0 0
MCA* 21 20 0 0 38 0 3
Syndromes 32 50 5 (10%) 1 (1.6%) 120 7 (5-8%) >26

CP
Pure 100 121 4 (3-3%.) 3 (1-5%) 430 4 (0-9%) 7
1 minor 10 19 3 (15.8%) 1 (5%) 55 1 (1.8%) >2
>2 minor 2 0 0 0 4 0 ?
I major 5 6 1(16.7%) 0 15 0 2
1 major + 1minor 1 ? ? 0 ? ? ?
MCA* 10 17 4 (23.5%) 0 8 1 (12-5%Y.) 1
Syndromes 42 51 2 (3.9%) 4 (4-8%) 208 3 (1-4%) 8

*MCA, multiple congenital anomalies (includes 'private' syndromes).

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An epidemiological study offacial clefting in Manitoba

TABLE 6 Sib recurrence rates as function ofpresence of cleft in relatives and malformations in proband

Affected Proband CP CLP
relative Total sibs No of affected Frequency Total sibs No of affected Frequency

None No malformation 97 1 1% 231 4 1.7%
> 1 minor 12 1 8% 22 1 4.6%
1 major ± minor 2 0 - 4 0 0%

Parent No malformation 0 0 - 8 0 0%
A 1 minor 2 1 50% 0 0 -
I major ± minor 0 0 - 0 0 -

2nd degree No malformation 15 2 13.3% 25 3 12%
> 1 minor 0 0 - 0 0 -
I major ± minor 0 0 - 0 0 -

> 3rd degree No malformation 27 1 3*7% 47 2 4.3%
>1 minor 11 1 9.1% 5 1 20%
1 major ± minor 0 0 - 0 0 -

are influenced by both the presence of clefts in
relatives and of malformations in the proband. In
table 6 the sib recurrence rates are presented as a
function of both these variables. The numbers are
too small to draw any conclusions, but presented in
this way the data could be combined with additional
series. However, there is a suggestion that higher sib
recurrence rates are associated with the presence of
minor anomalies when either no relative or a third
degree relative is affected, and with no minor
anomalies when a second degree relative is affected.
If this trend were to continue with larger numbers it
might provide clues as to the aetiological hetero-
geneity in cases of CLP and CP. Our numbers were
not large enough to reflect meaningfully on the
possible effects of the severity of the defect or the
sex of the proband on recurrence rates. However, the
data in the Appendix are in a form that could be
combined with additional studies. In addition,
pedigrees of the familial cases are available from the
authors on request.

In conclusion, this study has provided incidence
rates for the different forms of facial clefting in
Manitoba and has confirmed an ethnic variation in
incidence. The recurrence rates among sibs have
been shown to be strongly influenced by the presence
of affected relatives other than the proband and of
malformations in the proband. There is a suggestion
that these latter two variables maynot be independent.
It is clear that facial clefts have diverse aetiologies
and that only by precise analysis of cases subdivided
according to their physical and family history and
demographic data will it be possible to obtain
meaningful insights into the aetiologies and genetics
of CLP and CP. Unfortunately, as one continues to
subdivide into categories, the requirements for
greater numbers of cases and for accuracy of
recording increase and it becomes increasingly
difficult for one centre to obtain adequate data. Our
study suffers the defects of a retrospective study,

including loss of cases and incomplete data. This is
particularly true with respect to family history
information and the recording of minor anomalies.
For this reason we believe that a long-term, pro-
spective, multicentre study with standard recording
of family history, assessment of minor and major
malformations, face shape, and follow-up may be
required to provide answers to the questions that
remain regarding the genetics and counselling of
CLP and CP.

We are grateful to the many patients and their
physicians who co-operated in this study; to Dr J L
Hamerton who allowed us to use population data
collected in his newborn chromosome survey; to Drs
J A Evans, P W Hsu, and F C Fraser for encourage-
ment and guidance; and to Mr Ken Carpenter and
Ms Barb Ruchkall of the University of Manitoba
Computer Department for assistance in analysing
the data. This work was submitted as partial fulfil-
ment of a B.Sc in Medicine at the University of
Manitoba and was funded by the Children's Hospital
of Winnipeg Research Foundation. Mrs Lilian
Gordon patiently typed the numerous revisions of
the manuscript and the appendix.

References

1 Fraser FC, The genetics of cleft lip and cleft palate.
AmJHum Genet 1970;22:336-52.

2 Drillien CM, Ingram TTS, Wilkinson EM. The causes and
natural history of cleft lip and palate. Edinburgh: Living-
stone, 1966.

3 Hay S. Incidence of selected congenital malformations in
Iowa. AmJEpidemiol 1971 ;94:572-85.

4 Greene JC. Epidemiology of congenital clefts of the lip
and palate. Public Health Rep 1963 ;78:589-602.

5 Woolf CM. Congenital cleft lip. J Med Genet 1971;8:
65-83.

o Bear JC. A genetic study of facial clefting in northern
England. Clin Genet 1976;9:277-84.

7 Chi SCC. Cleft lip and cleft palate in New South Wales.
Aust Dent J 1974;19:111-7.

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132

8 Emmanuel I, Culver BH, Erickson JD, Guthrie B,
Schuldberg D. The further epidemiological differentiation
of cleft lip and palate: a population study of clefts in
King County, Washington, 1956-1965. Teratology 1973 ;7:
271-82.

9 Mitchell SC, Korones SB, Berendes HW. Incidence of
congenital heart disease in 56,109 births. Circulation
1971 ;43:323-32.

10 Statistics Canada. Vital statistics. Dominion Bureau of
Statistics Annual Report, Canada, 1970.

I Burdi AR. Epidemiology, etiology and pathogenesis of
cleft lip and palate. Cleft Palate J 1977;14:262-8.

12 Lowry RB, Renwick DHG. Incidence of cleft lip and
palate in British Columbia Indians. J Med Genet 1969;6:
67-9.

13 Fujino H, Tanaka K, Sanui Y. Genetic study of cleft lips

Joan Welch and Alasdair G WHunter

and cleft palates based upon 2828 Japanese cases.
Kyushi J Med Sci 1963;14:317-31.

14 Falconer DS. The inheritance of liability to certain
diseases, estimated from the incidence among relatives.
Ann Hum Genet 1965;29:51-71.

15 Woolf CM, Woolf RM, Broadbent TR. Cleft lip and
palate in parent and child. Plast Reconstr Surg 1969;44:
436-40.

16 Woolf CM, Gianas AD. A study of fluctuating dermato-
glyphic asymmetry in the sibs and parents of cleft lip
propositi. AmJHum Genet 1977;29:503-7.

Requests for reprints to Dr Joan Welch, 495 St
Anthony Avenue, Winnipeg, Manitoba R2V OS4,
Canada.

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