R K. KENUEETAL.

Cytogenetic Analysis of Children Suspected of

Chromosomal Abnormalities
by R. K. Kenue,* PhD, A. K. Guru Raj,** MRCP, P. F. Harris,* MD, and M. S. El-Bualy,** FAAP
*Cytogenetics Laboratory, Department of Human & Clinical Anatomy, and **Department of Child Health,
College of Medicine, Sultan Qaboos University, PO Box 35, Al-Khod, Muscat, Postal Code No. 123,
Sultanate of Oman

Introduction
Chromosome mutations can cause complex phenotypes associated with multiple congenital anomalies
and other defects in children. Consecutive newborn
surveys have shown that 29 per cent of children with
chromosomal abnormalities have multiple anomalies
at birth. 1 Although other factors are also known to
cause similar effects (e.g. teratogenic agents), it is
important to identify precisely the role of chromosomal imbalance, both for accuracy of diagnosis and
genetic counselling. The rate of chromosomal abnormalities is known to be significantly higher in selected
clinical populations than in an unselected
population. 2 " 19
In the present study we report the results of
cytogenetic studies performed on 122 Omani pediatric
patients in whom chromosomal abnormalities were
suspected.
Materials and Methods
The study sample consisted of 122 Omani children
referred for cytogenetic analysis because either they
had features suggestive of an abnormal chromosomal
syndrome or they were in one or more of the following
categories: multiple malformations, dysmorphic features, short stature of unknown cause in females,
mental retardation with dysmorphic features, ambiguous genitalia. Children with known non-chromosomal causes of anomalies, were excluded from this
study.
Acknowledgements
The authors thank the staff of the Department of Child
Health, S.Q.U.H. and the Photographic section, Centre of
Education Technology, S.Q.U. for their help in this study.
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The patients, whose ages ranged from newborns to

13 years, were referred from the Department of Child
Health, Sultan Qaboos University Hospital. These
children came from different parts of Oman, as this is
the only hospital providing cytogenetic service. However, this is not a representative sample for Oman.
Chromosomes were prepared from 72 hours peripheral blood lymphocyte culture according to the
established methods. Metaphase or prometaphase
chromosomes were analysed by conventional staining
(non-banding) and G-banding techniques. Q- and Cbanding were done where necessary. At least 20
metaphases were scored for each patient, 3-5 cells
being karyotyped. In patients with mosaicism, 50-100
metaphases were scored.
Results
The results are summarized in Tables 1,2 and 3. Of 122
children referred for chromosomal analysis, 50 (41 per
cent) had chromosomal abnormalities. Eighty-two per
cent of the patients (42/51) referred as having a known
chromosomal syndrome were aneuploid. Eleven per
cent of the remaining patients (8/71) with suspected
chromosomal abnormalities had an abnormal karyotype.
The largest cytogenetically abnormal group was
Down's syndrome (31 per cent). In 84 per cent of these
(32 children), free trisomy 21 was found. Five translocation Down's children from one family were observed
in the present study. Their mother was the carrier of
Robertsonian translocation. Only one patient with
mosaic Down's was observed (3 per cent of Down's
group).
Excluding Down's syndrome, chromosomal abnormalities were observed in 14 per cent patients (12/84).
Two infants with trisomy 18, one with trisomy 13, and
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Summary
Karyotypes were examined in 122 Omani children suspected of having chromosomal abnormalities. A
total of 50 (41 per cent) had an abnormal karyotype: 38 (31 per cent) were Down's syndrome whilst a
further 12 (10 per cent) had other types of chromosomal abnormalities. These findings suggest that
cytogenetic analysis is useful in the investigations of children with congenital anomalies of unknown
origin; to confirm clinical diagnosis in children with known cytogenetic syndromes and for genetic
counselling.

R. K. KENUEET AL

TABLE 1

Clinical diagnoses in patients referred for cytogenetic studies

No. of patients referred

Down's syndrome
Edward's syndrome
Patau's syndrome
Turner's syndrome
Multiple congenital anomalies/dysmorphic features, short stature of
unknown cause in females/mental retardation with dysmorphic features/
ambiguous gcnitaha
Total

No. of patients
cytogenetically
atmormal

41

37
2
1
2

5
2
3
71

50

122

1 case of trisomy 21, 1 case of 45,X/46,XX.

Karyotype

No. of cases

47,XY, + 21
47,XX, + 21
46,XY,-14, + t (14q; 21q)
46,XX,-14, + t (14q; 21q)
46,XX/47,XX, + 21
47,XX,+ 18
47,XY,+ 18
46,XY/47,XY,+ 13
45,X
45.X/ 46,XX
46,XY/47,XY, +marker
46,XX/47,XX,+ marker
46.XY, inv (5)(ql4q23)
46,XX/ 46.XX, del 7 (q31)

19
13
2
3
1
1
1
1
2
1
2
1
1
1

TABLE 3

Categories and incidence of chromosome abnormalities

identified in the study population
No. of
patients
Normal
Down's syndrome
Trisomy 18
Trisomy 13
Mosaic trisomy 13
Turner's
Mosaic Turner's
Intrachromosomal
structural aberrations
Supernumerary marker
chromosomes
Total

78

72
38
2
1
1
2
1
2

59.0
31.2

2.5

122

99.9

1.6
0.8
0.8
1.6
0.8
1.6

Clinical diagnosis
Down's syndrome
Down's syndrome
Down's syndrome
Down's syndrome
Microcephaly/mental retardation
Edward's syndrome
Edward's syndrome
Agenesis of corpus callosum
Turner's syndrome
Dysmorphic features
Ambiguous genitalia
Hypogonadism
Mental redardation/dysmorphic features
Mental retardation/ dysmorphic features

one with mosaic trisomy 13 were observed. Two girls

with Turner syndrome had 45,X chromosome constitution and one girl referred with dysmorphic features
was a mosaic 45VX/46,XX.
Intrachromosomal structural rearrangements were
observed in two children; one boy had inversion of
chromosome 5 (ql4q23) and a girl had mosaic
interstitial deletion of chromosome 7 (q31). Supernumerary marker chromosome was found in mosaic
form in three children. The precise origin of the
markers could not be determined using available
techniques, as they were smaller than G-group chromosomes.
Discussion
The incidence of major chromosomal abnormalities in
consecutive newborn infants is 0.65 per cent and most
of these are balanced autosome rearrangements or sexchromosome abnormalities which do not produce
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TABLE 2

Abnormal karyotypes

R K. KENUE ET Al_

Journal of Tropical Pediatrics

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April 1995

with a chromosome abnormality is important as

recurrence risks are high in some cases. This helps
considerably in genetic counselling of families, especially in societies, such as in Oman, where avoidance of
major handicapping cytogenetic diseases by secondary
intervention (i.e. abortions) is not practiced.
References
1. Kalter H, Warkany J. Congenital malformations. Etiologic factors and their role in population (Part I). N Engl J
Med 1983; 308: 424-31.
2. Bochkov NP, Kuleshov NP, Chebotarev AN, Alekhin
VI, Midian SA. Population cytogenetic investigation of
newborns in Moscow. Humangenetik 1974; 22: 139-52.
3. Farhud DD, Walizadeh Gh-R, Kamali MS. Congenital
malformations and genetic disease in Iranian infants.
Hum Genet 1986; 74: 382-5.
4. Van Regemorter N, et al. Congenital malformations in
10,000 consecutive births in a university hospital; need
for genetic counselling and prenatal diagnosis. J Pediat
1984; 104: 386-90.
5. Winter RM, Ridler MAC, McKeown JA. A diagnostic
survey of infants referred for chromosome analysis in the
neonatal period. Br Med J 1980; 281: 1045-7.
6. Stoll C, Roth M-P, Dott B, Bigel P. Usefulness of a
registry of congenital malformation for genetic counseling and prenatal diagnosis. Clin Genet 1986; 29: 204-10.
7. Borovic CL, et al. Chromosome abnormalities in selected
newborn infants with malformations in Brazil. Am J Med
Genet 1989; 34: 320-4.
8. Mascarello JT, Hubbard V. Routine UK of methods for
improved G-band resolution in a population of patients
with malformations and development delay. Am J Med
Genet 1991; 38: 3 7 ^ 2 .
9. Tharapel AT, Summitt RL. A cytogenetic survey of 200
unclassifiable mentally retarded children with congenital
anomalies and 200 normal controls. Hum Genet 1977;
37: 329-38.
10. Coco R, Penschaszadeh VB. Cytogenetic findings in 200
children with mental retardation and multiple congenital
anomalies of unknown cause. Am J Med Genet 1982; 12:
155-73.
11. Sutherland GR, Murch AR, Gardiner AJ, Carter RF,
Wiseman C. Cytogenetic survey of a hospital for the
mentally retarded. Hum Genet 1976; 34: 231-45.
12. Griepenberg U, Hongell K, Knutila S, Kahkonen M,
Leisti J. A chromosome survey of 1062 mentally retarded
patients. Evaluation of a long-term study at the Rinnekoti Institution, Finland. Hereditas 1980; 92: 223-8.
13. Fryns JP, Kleczkowska A, Kubien E, Van den Berghe H.
Cytogenetic findings in moderate and severe mental
retardation. A study of an institutionalized population of
1991 patients. Acta Paediatr Scand (Suppl) 1984; 31:
1-23.
14. English CJ, Davison EV, Bhate MS, Barrett L. Chromosome studies of males in an institution for the mentally
handicapped. J Med Genet 1988; 26: 379-81.
15. Singh DN. Cytogenetic study of individuals suspected of
chromosome abnormalities. Clin Pediat 1977; 16:
619-22.
16. Verma RS, Dosik H. Incidence of major chromosomal
abnormalities in a referred population for suspected
chromosomal aberrations: a report of 357 cases. Clin
Genet 1980; 17: 305-8.
79

Downloaded from tropej.oxfordjournals.org by guest on January 1, 2011

major clinical manifestation in newborn infants. 20

There is a wide variation, ranging from 2.5 9 -52.7 19 per
cent, in the incidence of chromosomal abnormalities in
selected clinical populations as reported by different
investigators. 2 " 19 Although the present study has
shown a high incidence of chromosome abnormalities
(41 per cent) in selected children from Oman, a
comparison of our results with other reports in
literature is difficult, due to the different criteria
employed for patient selection and in the techniques
utilized.
In certain studies only newborn infants with multiple congenital anomalies were investigated for chromosomal abnormalities, 2 " 8 the incidence ranging
between 9.5 6 -42.8 ! per cent, but our study population
comprised of children up to the age of 13 years. In
another group of studies, chromosome abnormalities
in children with multiple congenital anomalies associated with mental retardation were investigated with
the exclusion of Down's syndrome or known chromosome syndromes, 9 ' 10 the incidence ranged between
21 9 -28 1 0 per cent.
Other investigators have cytogenetically evaluated
only mentally retarded individuals, 11 ~ 14 with an
incidence of 33 per cent reported in one study.' 2 A few
reports in literature 15 ~ 19 have given incidence of
chromosome aberrations in all individuals suspected
of chromosomal anomalies, ranging between
26 1 8 -53 1 9 per cent. The incidence of chromosome
abnormalities in the present study does fall within the
range of other reported incidences for the selected
populations.
The incidence of Down's syndrome was high in the
present study (76 per cent of the cytogenetically
abnormal). This could be attributable to (i) easy
detection at clinical examination, (ii) higher number in
the population because of significant improvement in
survival of these patients in Oman due to better health
services provided in recent times. Some authors have
postulated a direct relationship of consanguinity with
higher incidence of Down's syndrome 21 " 25 and consanguinity is common in Oman. However, other
reports have been unable to confirm increased consanguinity among parents of children with Down's
syndrome. 26 " 28
Amongst children with no known chromosomal
syndrome at the clinical examination, eleven per cent
were karyotypically abnormal. This incidence was
much higher than observed in unselected newborns. 20
The results of the present investigation and previous
reports 2 " 20 strongly support referral of children with
congenital anomalies and mental retardation of uncertain origin for chromosomal analysis. Even though
clinical diagnosis is accurate in major autosomal
trisomies, cytogenetic evaluation is essential to precisely identify the chromosome abnormality (e.g. to
differentiate translocation Down's from free trisomic
Down's). Accurate diagnosis is important for the
patient, family and physician. Recognition of parents

R K. KENUEETAL.

17. Shah V, Krishna Murthy DS, Murthy SK. Cytogenetic

studies in a population suspected to have chromosomal
abnormalities. Indian J Pediatr 1990; 57: 235-43.
18. Al-AwadiSA, Farag TI, Teebi AS, Naguib KK, Sundareshan TS, Krishna Murthy DS. Down syndrome in
Kuwait. Am J Med Genet (Suppl) 1990; 7: 87-88.
19. Nkanza NK, Tobani CT. Chromosomal abnormalities:
Experience in Harare hospital. E Afr Med J 1991; 68:
611-16.
20. Hook EB, Hamerton JL. The frequency of chromosome
abnormalities detected in consecutive studiesdifferences between studiesresults by sex and severity of
phenotypic involvement. In: Hook EB, Porter H (eds)
Population cytogenetic studies in human. New York:
Academic Press, 1977: 63-79.
21. Harlap S. Down's syndrome in West Jerusalem. Am J
Epidemiol 1974; 97: 225-32.
22. Hook EB, Harlap S. Differences in maternal age-specific
rates of Down syndrome between Jews of European

23.
24.
25.
26.
27.
28.

origin and North African or Asian origin. Teratology

1979; 20: 243-8.
Alfi OS, Chang R, Azen SP. Evidence for genetic control
of nondisjunction in man. Am J Hum Genet 1980; 32:
477-483.
Abeliovich D, Atia Y, Sarav D. Down syndrome in
Negev region. Am J Med Genet 1986; 25:'l83.
Farag TI, Teebi AS. Possible evidence for genetic
predisposition to nondisjunction in man. J Med Genet
1988; 25: 136-137.
Devoto M, et al. Frequency of consanguineous marriages
among parents of Down patients Hum Genet 1985; 70:
256-8.
Hammamy HA, Al-Hakkak ZS, Al-Taha S. Consanguinity and genetic control of Down syndrome. Clin Genet
1990; 37: 24-29.
Basaran N, Cenani A, Sayh BS, Ozkinay C, Artan S,
Seven H et al. Consanguineous marriages among parents
of Down patients. Clin Genet 1992; 42: 13-15.
Downloaded from tropej.oxfordjournals.org by guest on January 1, 2011

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