2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Phenotypic and genotypic spectrum of Arthrogryposis Multiplex Congenita using Next Generation Sequencing: Experience from a tertiary care centre in India

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The study aimed to investigate the clinical and genetic profiles of patients with Arthrogryposis Multiplex Congenita (AMC) in India using next-generation sequencing. AMC is a non-progressive disorder characterized by congenital contractures of two or more joints in different body areas and has an incidence of 1 in 2,000-3,000 live births. The study enrolled 67 families with a total of 79 affected individuals, ranging in age from 0-35 years (including 10 fetuses). Consanguinity was observed in 24% of families. The overall diagnostic yield was 53.7%, with the most common cause of AMC being variants in the ECEL1 gene.<br /><br />The study also identified 35 novel variants and observed a combination of autosomal dominant and autosomal recessive multilocus variants in the cohort. The diagnostic yield varied among different clinical categories, with the highest yield seen in distal arthrogryposis (DA). Early and severe presentation was more common in fetal akinesia deformation sequence (FADS) and neuromuscular etiology cases, and mortality was higher in patients presenting before one year of age.<br /><br />It was noted that clinical categorization may not always accurately predict the molecular etiology of AMC, suggesting limited accuracy in making a precise diagnosis based on clinical features alone. Molecular testing led to a revised diagnosis in 16% of the study subjects. The study emphasized the importance of next-generation sequencing in identifying multiple molecular diagnoses and expanding the phenotypic and genotypic understanding of AMC.<br /><br />The study concludes that the comprehensive analysis of clinical and genetic profiles using next-generation sequencing can significantly contribute to the understanding of AMC and aid in accurate diagnoses. However, further research is required to establish genotype-phenotype correlations in AMC. Acknowledgments were given to the patients, their families, and the funding support provided by the Indian Council of Medical Research (ICMR).

Asset Subtitle

Submitter Only - Neerja Gupta, MD Pediatrics, DM Medical Genetics; Presenting Author - Mounika Endrakanti, MD Pediatrics, DM Medical Genetics; Co-Author - Jyoti Sharma, M.Sc Bioinformatics; Co-Author - Mehar Chand Sharma, MD Pathology; Co-Author - Abdul S Ethayathulla, PhD; Co-Author - Punit Kaur, PhD; Co-Author - Shah Alam Khan, MS Orthopedics; Co-Author - Madhulika Kabra, MD Pediatrics;

Meta Tag

Bioinformatics

Bone/Joint Abnormalities

Etiology

Exome sequencing

Genetic Testing

Identification of Disease Genes

Musculoskeletal system

NextGen Sequencing

Co-Author Jyoti Sharma, M.Sc Bioinformatics

Co-Author Mehar Chand Sharma, MD Pathology

Co-Author Abdul S Ethayathulla, PhD

Co-Author Punit Kaur, PhD

Co-Author Shah Alam Khan, MS Orthopedics

Co-Author Madhulika Kabra, MD Pediatrics

Presenting Author Mounika Endrakanti, MD Pediatrics, DM Medical Genetics

Submitter Only Neerja Gupta, MD Pediatrics, DM Medical Genetics

Keywords

Arthrogryposis Multiplex Congenita

next-generation sequencing

diagnostic yield

ECEL1 gene

novel variants

distal arthrogryposis

fetal akinesia deformation sequence

mortality

molecular testing

genotype-phenotype correlations