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Table of Contents
ORIGINAL ARTICLE
Year : 2021  |  Volume : 70  |  Issue : 4  |  Page : 244-250

Cytogenetic evaluation of congenital anomalies in Manipur


1 Department of Anatomy, Maharishi Markandeshwar Medical College and Hospital, Solan, Himachal Pradesh, India
2 Department of Anatomy, Regional Institute of Medical Sciences, Imphal, Manipur, India

Date of Submission18-Aug-2020
Date of Acceptance01-Sep-2021
Date of Web Publication21-Dec-2021

Correspondence Address:
Dr. Garima Sharma
Department of Anatomy, Maharishi Markandeshwar Medical College and Hospital, Kumarhatti, Solan - 173 229, Himachal Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jasi.jasi_159_20

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  Abstract 


Introduction: Birth defect, congenital malformation, and congenital anomaly are synonymous terms used to describe structural, behavioral, functional, and metabolic disorders present at birth. Birth defects are the leading cause of infant mortality. The most common serious congenital disorders are heart defects, neural tube defects, and Down syndrome. The objective of the study is to determine the chromosomal abnormalities (structural and numerical) in congenital anomalies of suspected genetic causes, by peripheral lymphocytic culture and cytogenetic evaluation. Material and Methods: The study was a cross-sectional study undertaken for a duration of 2 years in a total of fifty cases of congenital anomalies with suspected genetic abnormalities. Peripheral blood from these cases was collected, and lymphocyte tissue culture was done for about 48–72 h. The best metaphase spread was selected, photographed, printed, and karyotypes were prepared. Findings of the study were then described by descriptive statistics. Results: Most common congenital anomalies were seen in the musculoskeletal system with 19 anomalies (38% of all cases) followed by genital organs with 12 anomalies (24% of all cases) and cleft lip and cleft palate with 8 anomalies (16% of all cases). Chromosomal anomalies were seen in six cases (12% of all cases). All were cases of Down syndrome and had trisomy 21. Discussion and conclusion: The present study might be of help in an earlier and better diagnosis of the cases of congenital anomalies, particularly the cases presenting with chromosomal abnormalities so that their counselling can be started at the earliest. It might be suggested that cytogenetic evaluation of cases of congenital anomalies should be included in routine investigation.

Keywords: Chromosomal abnormalities, congenital anomalies, Down syndrome, karyotyping


How to cite this article:
Sharma G, Devi AJ, Singh TN. Cytogenetic evaluation of congenital anomalies in Manipur. J Anat Soc India 2021;70:244-50

How to cite this URL:
Sharma G, Devi AJ, Singh TN. Cytogenetic evaluation of congenital anomalies in Manipur. J Anat Soc India [serial online] 2021 [cited 2022 Jun 26];70:244-50. Available from: https://www.jasi.org.in/text.asp?2021/70/4/244/333184




  Introduction Top


Birth defect, congenital malformation, and congenital anomaly are synonymous terms used to describe structural, behavioral, functional, and metabolic disorders present at birth. Birth defects are the leading cause of infant mortality, accounting for approximately 21% of infant deaths and 30%–50% of deaths after neonatal period. They are the fifth leading cause of potential life lost prior to 65 years of age and yield major contribution to disabilities.

Causes of malformations – in 40%–60% of cases of malformations, the cause of the birth defect is unknown. Genetic factors such as chromosomal abnormalities and mutant genes account for approximately 15% of cases. Environmental factors produce approximately 10% of cases. A combination of genetic and environmental influences (multifactorial inheritance) produces 20%–25% of cases; and twining contributes 0.5%–1%.[1]

The birth prevalence of congenital anomalies in the developing world is underestimated by deficiencies in diagnostic capabilities and lack of reliability of medical records and health statistics. The prevalence of birth defects in India (per 1000 live births) is 64.3. The contribution of birth defects to neonatal mortality rates is 9.6%, to perinatal mortality rate is 19.5%, and to stillbirths is 9.9%. The annual report of the Indian Council of Medical Research says that the most common congenital malformations are cardiac in nature. Cardiovascular, musculoskeletal, and genitourinary were the most commonly affected systems in a descending order of frequency. The most common serious congenital disorders are heart defects, neural tube defects, and Down syndrome.[2]

The laboratory evaluation of a malformation is helpful but complex. Cytogenetics with Giemsa-banded peripheral leukocyte karyotype (or chromosome analysis) is the gold standard and should be performed in most evaluations.[3]

The objective of the study is to determine the chromosomal abnormalities (structural and numerical) in congenital anomalies suspected of genetic causes, of outdoor and indoor patients, attending the Regional Institute of Medical Sciences Hospital, Imphal, by peripheral lymphocytic culture and cytogenetic evaluation.


  Material and Methods Top


The study was a cross-sectional study undertaken in the Department of Anatomy for a duration of 2 years. A total of fifty cases of congenital anomalies with suspected genetic abnormalities, of the outdoor and indoor patients, attending the Regional Institute of Medical Sciences, Imphal, were studied and cases with known teratogenic causes were excluded. The sample size was calculated by applying the nonprobability sampling technique of convenient/purposive sampling. Formal permission was sought from the Institutional Ethics Committee to take up this study. Informed consent was obtained from the parents and their data were collected. Antenatal history, perinatal history, present history, family history, age, sex, height, and phenotype were used as study variables. Type of abnormality and karyotype of the cases were the outcome variables. Peripheral blood from these cases was collected and lymphocyte tissue culture was done for about 48–72 h. Fifteen–twenty metaphase spread was examined under trinocular research microscope. The best metaphase spread was selected, photographed, printed, and karyotypes were prepared.

Data of the study were entered in a master chart using Microsoft Excel 2013 (Washington, USA). Data were analyzed by using appropriate charts and graphs. Percentage and ratio were calculated. Findings of the study were then described by descriptive statistics.


  Results Top


Sex

The study was done in 26 females (52%) and 24 males (48%) with congenital anomalies making a total of fifty cases. The ratio of female-to-male cases was 1.08:1. One of the 26 female cases was of the disorder of sexual development presenting with ambiguous genitalia, which was found to be a normal female on karyotype [Figure 1].
Figure 1: Shows ambiguous genitalia in a case of disorder of sexual development taken 3 days after birth

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Age

(A) Patient: Maximum number of cases were in the age group 0–5 years of age, 39 cases (78.0%), of which 16 (41.0%) were males and 23 (58.9%) were females. In this age group, 27 cases were <1 years of age, of which 16 were females and 11 were males. In the age group of 6–10 years, six cases (12.0%) were seen, with four (66.6%) males and two (33.3%) females. This was followed by three cases (6%) in the age group 11–15 years, with two males (66.6%) and one female (33.3%). Age groups of 16–20 and 21–25 years each had one case (2%), with both being males (100%). The youngest case was of 1 day and the oldest was of 21 years of age

(B) Mother: For the cases studied, the minimum age of conception for the mother was 16 years, with the maximum age being 45 years.

Birth order

The birth order in maximum cases, 19 cases (38%) were as a second child. The cases were delivered as a first child in 18 cases (36%), as a third child in 11 cases (22%), and as fourth and five children in one case each (2%). In one case, the child was delivered as twins. Hence, it can be concluded that cases of congenital anomalies were seen more in a multiparous mother (64%) as compared to a primiparous mother (36%).

Family history and consanguineous marriage

The family history was significant in three cases (6%) and consanguineous marriages were seen in four cases (8%). In all these four cases, parents were first cousins that is third-degree relatives.

Systemic involvement

Systemic involvement was classified as per the International Classification of Diseases (ICD, ICD 10 Version: 2016),[4] as depicted in [Table 1].
Table 1: The international classification of diseases classification of the types of anomalies

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As there is an overlap of anomalies, so the number of anomalies in [Table 1] is 61, which is higher than the total number of cases (50), as a single case may contain more than one anomaly.

Most common congenital anomalies were seen in the musculoskeletal system with 19 anomalies (38% of all cases), followed by genital organs with 12 anomalies (24% of all cases) and cleft lip and cleft palate with 8 anomalies (16% of all cases). Circulatory system had five anomalies (10% of all cases), followed by other congenital anomalies in four cases (8% of all cases) and anomalies of eye, ear, face, and neck in three cases (6% of all cases). Urinary system and nervous system each had two anomalies (4% of all cases). Chromosomal anomalies were seen in six cases (12% of all cases), out of the total fifty cases studied [Table 1].

Karyotype

Karyotypes observed and their interpretation are shown in [Table 2]. Six cases of abnormal karyotype were seen. All were cases of Down syndrome and had trisomy 21. All cases presented with dysmorphic features. They also presented with jaundice, birth asphyxia, distended abdomen, bronchopneumonia and jaundice, midline abdominal wall defects with hypospadias with club foot, and heart defects.
Table 2: The karyotypes observed and their interpretation

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Phenotypically, all the cases showed mongoloid features such as a flat facial profile, an upslanting palpebral fissure, and an open mouth in varied combinations. All the cases had a broad flat depressed nasal bridge. One case had epicanthic folds and one case had small-sized ears. One case had deep creases in feet, two had proximally displaced toes, and three had wide gaps between toes, first and second as well as third and fourth. One case had talipes equinovarus in both feet and one case had clubbing with inverted feet. Simian crease was present in two cases, one in the right hand and one in both hands. One case had a single crease in the fifth little finger. A clenched fist was also seen in one case. A wide gap was seen between fourth and fifth fingers of the right hand with clubbing in all fingers, in the case with the heart defect. Neck appeared shorter in all cases with loose folds present in the posterior part of the neck in one case and a low hairline in one case each. External genitalia showed undescended testis right side in one case and penile hypospadias in one case. Two cases had hypotonia and one case had a midline abdominal wall defect. In terms of karyotype, four cases had 47, XY, and +21 and two cases had 47, XX, and +21 as their karyotype. All cases were eventually diagnosed to be Down syndrome with trisomy 21, nondisjunction [Figure 2], [Figure 3], [Figure 4], [Figure 5].
Figure 2: (a) Shows a case of Down syndrome presenting with a flat facial profile, upslanting palpebral fissure, and a flat nasal bridge. Rt (b) right foot. Lt (c) left foot. Both feet were inverted with clubbing. Wide gap was present between first and second toe and third and fourth toe. (d) Hands show clubbing with a wide gap between fourth and fifth finger. A single Simian crease is present on the left fifth finger

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Figure 3: (a) Shows a case of Down syndrome presenting with a flat facial profile, a broad nasal bridge. (b) Simian crease on the left hand

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Figure 4: Karyogram showing karyotype of a case of Down syndrome female 47, XX, +21

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Figure 5: Karyogram showing karyotype of a case of Down syndrome male 47, XY, +21

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In three instances, cases presenting with dysmorphic features were found to be normal on karyotyping.

In the first instance, an 11-day-old female baby presented with facial dysmorphism, jaundice, and low birth weight. The baby had a prominent occiput, small mouth, and a flat nasal bridge. Left foot had a proximally displaced great toe. Right foot had proximally displaced and dorsiflexed toes with synechiae between first and second and third and fourth toes. Clenched fists were seen. Hypertonia was present. The karyotype of the baby was found to be normal, 46, XX [Figure 6]. In the second, a 14-year-old male presented with mental retardation and anemia. The child had a flat facial profile with a flat depressed nasal bridge. Epicanthal folds were present. Neck appeared shorter. Mild scoliosis was present. There was a lateral deviation of the first toe of the left foot. Abdomen was distended. Karyotype of the child was normal, 46, XY [Figure 7]. In the third, a 21-year-old male presented with hypoplasia of the penis and small testis since childhood. Secondary sexual characteristics were absent with no pubic hair and axillary hair. Learning disabilities were present since childhood. Tall and slim stature was also noted. Karyotype showed a normal result, 46 XY.
Figure 6: (a) Shows a case presenting with a prominent occiput, flat nasal bridge, clenched fist, and hypertonia. (b) shows proximally displaced and dorsiflexed toes, synechiae between first and second and third and fourth toes

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Figure 7: A case with flat facial profile, epicanthal folds, flat depressed nasal bridge, and a short neck

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  Discussion Top


The findings of the present study are elaborated, compared, and discussed with the findings of the previous studies.

Sex

There are many reports on the incidence of congenital anomalies, being more in females. One study reported a female-to-male ratio of 1.6:1[5] and another studied 51.1% of females and 48.3% of males.[6] Similarly, in the present study, 52% of cases were of the female sex and 48% of cases were of the male sex. The female-to-male ratio was 1.08:1.

Age

The spectrum of age in cases of congenital malformations varied in previous studies, ranging from birth to 50 years with a mean of 14.3 years,[5] few hours after birth to 15 years,[7] and 1 day to 14 years of age.[8] In the present study, the age of cases ranged from 1 day to 21 years of age and this variation in the age may be due to nature of the study. Maximum number of cases were in the age group of up to 5 years of age.

Birth order

The findings in the present study indicate that congenital anomalies were common in multiparous mothers (64%). This finding is almost similar to the available literature.[2],[9],[10],[11],[12],[13],[14] The maximum cases in the present study were born as a second child, a finding was also seen earlier.[13]

Consanguineous marriage

In the present study, 8% of cases of congenital anomalies had parents with consanguineous marriages. Previously, consanguineous marriages have been reported to be 8.16%,[15] 8.1%,[9] and 8.5%[13] in cases of congenital malformations. Effect of low sample size on the incidence, and prohibition of consanguineous marriages among the Meitei population, to which the maximum number of cases belong, may be a reason for the low incidence of consanguinity seen in the present study.[24]

Systemic involvement

The comparison of the present study with others on the basis of systemic involvement is described in [Table 3].
Table 3: The type of anomalies as reported by different authors

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The difference in the percentage of anomalies can be explained by different nomenclature used for classifying the anomalies. In the present study, ICD (ICD 10 Version: 2016) classification for congenital anomalies is followed.

Karyotype

The findings of the present study, with reference to the percentage of chromosomal abnormal cases found, are compared to the other studies, in the [Table 4].
Table 4: The percentage of chromosomal anomalies as reported by different authors in comparison to the present study

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As can be seen from the table, the findings of the present study are comparatively less than some authors but are extremely less in comparison to some. This can be explained due to a variable sample size in all studies, due to some undetectable causes by simple karyotyping in some of the cases, and a very small sample size in the present study.

In the present study, among the abnormal karyotypes, all cases, i.e. 100%, were of Down syndrome and all of them had trisomy 21 (100%). The comparison of the present study with other studies, with respect to the type of abnormality, is given in [Table 5].
Table 5: The comparison of the present study with other authors according to the type of chromosomal abnormality seen

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  Conclusion Top


The present study might be of help in early and better diagnosis of the cases of congenital anomalies, particularly the cases presenting with chromosomal abnormalities so that their counseling can be started at the earliest. This study has also shown the limitation of the normal karyotyping in detection of genetical defects. It might be suggested that cytogenetic evaluation of cases of congenital anomalies should be included in their routine investigation.

Acknowledgment

We acknowledge constant cooperation and help of the faculty and staff of Department of Anatomy, Regional Institute of Medical Sciences, Imphal, during the study period. We also acknowledge Department of Biotechnology, Nodal cell, Tezpur University, for financial support for completion of this research work.

Financial support and sponsorship

Department of Biotechnology, Ministry of Science and Technology, Nodal Cell, Tezpur University, Assam.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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