Congenital Anomalies in a Neonate With Partial Monosomy of Chromosome 21 q Arm - A Case Report - Whole Genome Sequencing

Sep 30, 2026

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Congenital anomalies drive substantial infant morbidity and mortality. Whole-genome sequencing (WGS) supports diagnosis when conventional testing yields complex or unclear results. This case report describes an Indian neonate with holoprosencephaly and multiple associated anomalies, including dysmorphic features and a ventricular septal defect. Karyotype analysis showed mitotic instability with ring chromosome 21 and 21q-arm deletions. WGS further defined a partial monosomy in the 21q22.11-q22.3 region, enabling precise detection of copy number variation and complex structural variants and clarifying the genetic basis of the presentation.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages25

Reading Time1 h 3 min

AccessFree to download

Introduction

Methods

Case Presentation

Materials and methods

Ethical Clearance

Whole Genome Sequencing and Preprocessing

Open Access Case Report Review began 11/29/2025 Review ended 12/06/2025 Published 12/08/2025 © Copyright 2025 Joy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0. , which permits unrestricted use , distribution , and reproduction in any medium , provided the original author and source are credited. DOI: 10.7759/cureus.98751 Congenital Anomalies in a Neonate With Partial Monosomy of Chromosome 21 q Arm: A Case Report Praisy Joy 1 , Sudeshna Datta 2, Sanjukta Sahoo 1 , Tapas Kumar Som 3, Prabhas R. Tripathy 1 , Manisha R. Gaikwad 1 , Pavithra Ayyanar 4, Sunil K. Raghav 2 1. Department of Anatomy, All India Institute of Medical Sciences, Bhubaneswar, Bhubaneswar, IND 2. Immunogenomics and Systems Biology Laboratory, Institute of Life Sciences, Bhubaneswar, IND 3. Department of Neonatology, All India Institute of Medical Sciences, Bhubaneswar, Bhubaneswar, IND 4. Department of Pathology and Laboratory Medicine, All India Institute of Medical Sciences, Bhubaneswar, Bhubaneswar, IND Corresponding author: Praisy Joy, [drpraisyjoy@gmail.com](drpraisyjoy@gmail.com) Abstract Congenital anomalies are a major cause of infant morbidity and mortality. Whole-genome sequencing provides a potential tool for solving diagnostic dilemmas in such instances. We report an interesting case of a neonate from India with holoprosencephaly and multiple associated anomalies, including dysmorphic features and ventricular septal defect. Karyotype analysis revealed mitotic instability. Both ring chromosome 21 and deletions in the q arm of chromosome 21 were observed in the metaphase spreads. To characterize the genomic abnormality more precisely, whole genome sequencing was performed, which identified a partial monosomy involving the 21q22.11-q22.3 region. This case demonstrates how whole-genome sequencing effectively identifies copy number variations and complex structural abnormalities, providing valuable insights into the genetic basis of congenital abnormalities. Categories: Genetics Keywords: 21q deletion, congenital anomalies (ca), next generation sequencing (ngs), partial 21 monosomy, ring chromosome 21, structural variants (sv), whole genome sequencing (wgs) Introduction A congenital anomaly (CA) is defined as “a structural, functional, behavioural, or metabolic abnormality present during the intrauterine period that may be detected prenatally or at birth” [1] . CAs profoundly impact the health and well-being of individuals, families, healthcare systems, and communities, as they cause early miscarriage and fetal and infant death. They can be classified as major or minor anomalies according to the International Classification of Disease guidelines by the World Health Organization [2] . Major anomalies affect the infant’s life expectancy and physical or social functions, whereas minor anomalies have little or no impact on health [2] . Although CAs occur globally, its burden is higher in developing countries [3] . In India, the incidence ranges from 0.84% to 2.9%, making it the fourth leading cause (8 .6%) of neonatal mortality and the sixth leading cause of under-five mortality [4] . Common anomalies are neural tube defects, congenital heart diseases, cleft lip and palate, and limb abnormalities. With the emergence of 4D ultrasound and advances in sequencing techniques, the trend in detection has increased over the years. There is a genetic aetiology in 30-40% of such cases. Methods to understand the aetiology of CA include karyotyping, fluorescence in situ hybridisation (FISH), comparative genomic hybridization (CGH) array, and next-generation sequencing (NGS) techniques. In recent times, NGS is one of the most powerful methods for the diagnosis of congenital abnormalities and rare Mendelian disorders. It is widely used to detect single-nucleotide variants (SNVs) and structural variants (SVs) [5] . SVs are large genomic alterations of at least 5

FAQs

What genetic abnormality was identified in this neonate?

Karyotype analysis revealed ring chromosome 21 and deletions on the long arm of chromosome 21. Whole-genome sequencing identified a partial monosomy involving the 21q22.11-q22.3 region.

Which clinical anomalies were reported in the case?

The neonate had holoprosencephaly and multiple associated anomalies, including dysmorphic features and a ventricular septal defect.

How did whole-genome sequencing contribute to diagnosis?

WGS precisely characterized the genomic abnormality and enabled detection of copy number variations and complex structural abnormalities, providing insight into the genetic basis of the congenital anomalies.

Sep 30, 2026

Uploaded by moss~