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Year : 2020  |  Volume : 13  |  Issue : 6  |  Page : 677-680  

Maternal 2:18 chromosomal translocation manifesting as cause for developmental delay in a proband

Department of Anatomy, Dr. DY Patil Medical College, Hospital and Research Centre, Dr. DY Patil Vidyapeeth, Pune, Maharashtra, India

Date of Submission03-Oct-2019
Date of Decision03-Apr-2020
Date of Acceptance25-Jun-2020
Date of Web Publication6-Nov-2020

Correspondence Address:
Purushottam Rao Manvikar
Department of Anatomy, Dr. DY Patil Medical College, Hospital and Research Centre, Dr. DY Patil Vidyapeeth, Pimpri, Pune, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mjdrdypu.mjdrdypu_274_19

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Developmental disabilities are a group of related chronic disorders of early onset and said to affect 5% to 10% children. Mental Retardation or intellectual disability has been redefined and replaced with Global developmental delay by WHO as the parameters of diagnosis of such a condition become valid and reliable by the age of five years of the proband. In Indian context the incidence is 2.5%.Chromosomal aberrations either structural or numerical account for 25-30% in general population. Chromosomal analysis and karyotyping is considered as primary investigation in management protocols of such children. Authors present a case of six months old child referred to cytogenetic laboratory with a clinical suspicion of delayed mile stone. Proband was born to a non-consanguineous couple delivered by lower segment caesarian section (LSCS) with no untoward incidents during intraoperative and post-operative phase of surgery. There was history of earlier fetal loss at third month of gestation due to cardiac defects diagnosed prenatally. Karyotyping of proband revealed 2:18 translocation. Karyotype of parents was done to find out the source of translocated chromosome. It was revealed that 2:18 translocated chromosome was seen in karyotype of mother of proband. Karyotype of proband was reported as 46,XX; der(18) t(2:18)(q31q35 ;q21q22)mat As per ISCN guidelines. Case has been reported for the rarity of such an occurrence.

Keywords: Developmental delay, intellectual disability, mental retardation, translocation

How to cite this article:
Manvikar PR, Awari P. Maternal 2:18 chromosomal translocation manifesting as cause for developmental delay in a proband. Med J DY Patil Vidyapeeth 2020;13:677-80

How to cite this URL:
Manvikar PR, Awari P. Maternal 2:18 chromosomal translocation manifesting as cause for developmental delay in a proband. Med J DY Patil Vidyapeeth [serial online] 2020 [cited 2021 Jun 14];13:677-80. Available from: https://www.mjdrdypv.org/text.asp?2020/13/6/677/300140

  Introduction Top

Developmental disabilities are a group of related chronic disorders of early onset and said to affect 5%–10% of children. These disabilities once categorized under intellectual disabilities could be diagnosed by the time the child reaches the age of 5 years when standard measures of intelligence become reliable and valid. Term mental retardation (MR) which was in vogue is merged with intellectual disability now replaced by global developmental delay (GDD) which in turn is defined as the delay in attainment of developmental milestones at the expected age and is implied by deficits in learning and adaptation.[1]

The incidence of GDD is 1%–3%.[2],[3],[4] As per the World Health Organization, the worldwide incidence of the same is about 5% in children <14 years of age.[5] In Indian children, below 2 years of age, the number is 2.5%.[6] Chromosomal abnormality, either numerical or structural, is one of the etiological factors for GDD. The incidence reported is 25%–30% in the general population.[7],[8]

In view of the magnitude of this problem, the authors report the case of a 6-month-old child referred for karyotyping to the Cytogenetic Laboratory, Department of Anatomy, by the pediatricians of Dr. DY Patil Medical College, Hospital and Research Centre, Pune, with the provisional clinical diagnosis of developmental delay.

  Clinical History Top

The proband was born to nonconsanguineous couple. However, there was uncle–niece consanguinity on the paternal side in grandparents [Figure 1]. Delivered by lower segment cesarean section at the 38th week of gestation, there was no event of fetal hypoxia, and the child cried immediately after birth. The Apgar score was 7/10 at 1 min and 9/10 at 5 min. The birth weight of the child was 2.7 kg. Exposure to teratogens of any sort and history of infection and major illness of mother during pregnancy were not found. However, there was one incidence of medical termination of pregnancy done at the 3rd month due to a cardiac anomaly in the fetus, which was detected by ultrasonography, but the details of the cardiac anomaly were not available. The child presented with dysmorphic face, epicanthal folds, and hypertelorism. Partial neck holding was present. After taking due consent from the parents as per protocol, karyotyping of the proband was done with conventional microculture and GTG banding of peripheral lymphocytes. Two milliliters of blood sample was collected in heparinized tubes, cultured, and lymphocytes were harvested. On chromosomal analysis, additional material on the long arm of chromosome 18 was detected in the proband. Metaphase spread count was increased to 100, and all the spreads showed additional chromosomal material at 18q. The rest of the chromosomes were normal and did not match with a clear translocation. To find the source of this additional material on chromosome 18 in the proband, karyotyping of the parents was undertaken. Karyotype of the father [Figure 2] was normal, i.e., 46XY. However, in mother, a balanced insertional translocation of part of the long arm of the chromosome 2 on chromosome 18 was observed. Mother's karyotype [Figure 3] was 46, XX;t(2:18) (q31q35;q21q22). This suggested that the abnormal chromosome in the child was the result of the transmission of structural rearrangement from the mother. The karyotype of the child [Figure 4] was 46;der(18) t(2:18)(q31q35;q21q22) mat. signifying that this additional genetic material is derived from the mother. This additional load of the genome on the chromosome 18 seemed to be the etiolgical factor for the developmental delay in the proband. Confirmation by fluorescent in situ hybridization was suggested, and the case was referred to the department of pediatrics for further management.
Figure 1: Pedigree chart

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Figure 2: Karyotype of father: 46,XY

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Figure 3: Karyotype of mother 46,XX;t(2:18)(q31q35;q21q22)

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Figure 4: Karyotype of the proband: 46,XX; der(18) t(2:18)(q31q35;q21q22)mat

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  Discussion Top

Genetic mutations can be duplication, deletion, or rearrangement of DNA. The changes in chromosome structure which are large enough to be detectable under the light microscope are called as chromosome aberrations. Structural abnormalities occur as a result of chromosomal breakage and abnormal reunion. Synapse between homologous regions of nonhomologous chromosomes may lead to accidental recombination between nonhomologous chromosomes, leading to translocation. The insertional translocations are less common. They may occur within a chromosome or between two chromosomes. The balanced carrier of such insertion translocations will be healthy, but the segregation of two translation derivatives during meiosis will lead to an unbalanced state in the proband with either deletion or duplication of inserted segment. Parents with balanced chromosomal translocations may deliver a live-born infant with varying degrees of developmental abnormality depending on the nature of the chromosomal imbalance.[9]

Little experimental evidence exists on the meiotic behavior of insertional translocations, but a theoretical analysis shows that at least 26 possible segregants can result from the meiotic process.[10] If the inserted fragment is large, a quadrivalent with a loop might be formed allowing complete pairing of the chromosomes involved in the rearrangement.[11],[12]

Mechanism of translocation

In the present case, the quadrivalent which might have been formed in maternal gametogenesis is shown in [Figure 5]. Out of 26 different possibilities of segregation, the maternal gamete containing normal chromosome 2 and the derived chromosome 18 might have been fertilized by parental gamete [Figure 6], leading to the karyotype 46XX; der(18) t(2:18) (q31q35;q21q22) mat in the proband.
Figure 5: Quadrivalent formation at the time of oogenesis

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Figure 6 : Zygote formation by fusion of gametes

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In carriers of balanced translocation, the possible reason for the association of congenital malformation could be gene inactivation or disruption at the breakpoint.[13]

Rajasekhar et al. had reported various cases of developmental delay with translocation.[14]

Usha Dave et al. have mentioned chromosomal translocations as the cause of MR in 5.7% of people in the Indian population.[15]

To the best of our knowledge, this seems to be the first reported case of maternal 2:18 chromosomal translocation manifesting as delayed development in a proband.

Couples with genetic disorders including single gene defects, sex-linked conditions, or chromosome rearrangements face a reproductive risk. Preimplantation genetic diagnosis (PGD) is a diagnostic tool to avoid inheritance of chromosomal disease by transferring balancedin vitro fertilization (IVF) embryos and represents an alternative to prenatal diagnosis.[16] IVF can increase the chance of conceiving and decrease the probability of miscarriages and chromosomally unbalanced offspring. The results of PGD chromosomal translocation carriers are comparable with regular IVF without PGD patients and allow a very significant reduction in the frequency of early pregnancy loss.[17]

  Conclusion Top

The chromosomal studies are mandatory in children with developmental delay.[18] Karyotyping of parents becomes essential in cases of insertional translocations to find out the source of additional chromatin material. The deletions and duplications of the part of chromosome may lead to various abnormal phenotypic features, but the translocations are scarcely seen as the cause of the developmental delay. Translocation carriers may contribute to delayed milestones in their offsprings. Genetic counseling of the couple is needed to plan further course of management for such children. This case was presented because of unique maternal translocation between chromosomes 2 and 18 as a cause of delayed development because of its rarity.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Shevell M, Ashwal S, Donley D, Flint J, Gingold M, Hirtz D, et al. Practice parameter: Evaluation of the child with global developmental delay: Report of the Quality Standards Subcommittee of the American Academy of Neurology and The Practice Committee of the Child Neurology Society. Neurology 2003;60:367-80.  Back to cited text no. 1
Munro JD. Epidmiology and extent of mental retardation. Psy Clin North Am 1986;9:591-624.  Back to cited text no. 2
Kabra M, Gulati S. Mental retardation. Indian J Pediatr 2003;70:153-8.  Back to cited text no. 3
de Vries BB, Pfundt R, Leisink M, Koolen DA, Vissers LE, Janssen IM, et al. Diagnostic genome profiling in mental retardation. Am J Hum Genet 2005;77:606-16.  Back to cited text no. 4
Albrecht G, Bartolomeos K, Chatterji S, Diamond M, Emerson E, Fujiura G, et al. Disability a Global Picture, Ch. 2. World Report on Disability, Published in Malta by World Health Organization; 2011. p. 53. Available from: https://www.who.int>report. [Last accessed on 2019 Jun 15].  Back to cited text no. 5
Nair MK, Radhakrishnan SR. Early childhood development in deprived urban settlements. Indian Pediatr 2004;41:227-37.  Back to cited text no. 6
Keren B. La déficience intellectuelle: Du diagnostic en puces ADN à l'identification de gènes candidats. Paris: Université René Descartes Paris V; 2013.  Back to cited text no. 7
Moeschler JB, Shevell M, Committee on Genetics. Comprehensive evaluation of the child with intellectual disability or global developmental delays. Pediatrics 2014;134:e903-18.  Back to cited text no. 8
David Rimon J, Connor M, Pyeritz R, Korf B. Emery and Rimon's Principles and Practice of Medical Genetics. Ch. 25, 4th ed. Vol. 1. Harcourt Publishers Limites, Elsevier Science Limited; 2002. p. 700,701,703.  Back to cited text no. 9
Melotte C, Debrock S, D'Hooghe T, Fryns JP, Vermeesch JR. Preimplantation genetic diagnosis for an insertional translocation carrier. Human Reproduction 2004;19:2777-83.  Back to cited text no. 10
Van Hemel JO, Eussen HJ. Interchromosomal insertions. Identification of five cases and a review. Hum Genet 2000;107:415-32.  Back to cited text no. 11
McKinley Gardner RJ, Sutherland GR, Shaffer LG. Chromosome abnormalities and genetic counselling. 3rd ed. New York: Oxford University Press ;2004.p163-77.  Back to cited text no. 12
Burns JP, Koduru PR, Alonso ML, Chaganti RS. Analysis of meiotic segregation in a man heterozygous for two reciprocal translocations using the hamsterin vitro penetration system. Am J Hum Genet 1986;38:954-64.  Back to cited text no. 13
Rajasekhar M, John N, Gopinath PM, Satyamoorthy K. A cytogenetic study of children with developmental delay mental retardation. International Journal of Human Genetics 2011;11:89-92.  Back to cited text no. 14
Dave U, Shetty D. Chromosomal abnormalities in mental retardation: Indian experience. Int J Hum Genet 2010;10:21-32.  Back to cited text no. 15
Verlinsky Y, Kuliev A. Current status of preimplantation diagnosis for single gene disorders. Reprod Biomed Online 2003;7:145-50.  Back to cited text no. 16
Otani T, Roche M, Mizuike M, Colls P, Escudero T, Munné S. Preimplantation genetic diagnosis significantly improves the pregnancy outcome of translocation carriers with a history of recurrent miscarriage and unsuccessful pregnancies. Reprod Biomed Online 2006;13:869-74.  Back to cited text no. 17
Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP, et al. Consensus statement: Chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2010;86:749-64.  Back to cited text no. 18


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


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