Objectives: This ongoing study aims to decipher the phenotypic and genomic spectrum of neurodevelopmental disorders (NDDs) in India.
Methods: A total of 440 families (473 individuals) with NDDs were recruited from October 2019 till February 2022. Genetic testing after detailed clinical evaluation was carried out.
Results: The cohort comprises 289 males (61%) and 184 females (39%) from 180 consanguineous (41%) and 260 non-consanguineous (59%) families. Notably, 440 (93%) affected individuals are of the pediatric age group. Pathogenic variants were detected in 253 families (58%): 25 (9%) by targeted testing,16 (6%) by chromosomal microarray and 216 (85%) by exome sequencing. Overall, 197 monogenic disorders were identified in 238 families (94%) and 14 chromosomal disorders in 15 families (6%). Monogenic disorders comprised of 49 genetic syndromes (25%), 42 metabolic disorders (21%), 24 leukodystrophies (12%), 18 disorders with epilepsy as a core symptom (9%), 14 neuromuscular disorders (7%), 13 cerebellar disorders (7%), 4 with basal ganglia involvement (2%), 7 hereditary spastic paraplegias (4%) and 26 other heterogeneous (13%). Of these, 126 were autosomal recessive (59%), 66 autosomal dominant (31%), 18 X-linked (9%), and one with mitochondrial inheritance (1%). Significant phenotypic and genotypic insights of the cohort include (i) Five novel disease-gene associations (GCSH, PIDD1, TMEM163, KCNH5, SNRPN) (ii) Novel disease-causing variants in 146 (56%) families (iii) Four families with multiple genetic diagnoses and (iv) identification of probable founder variants (ISCA1, RNASEH2C, CYB5R3) in the Indian population.
Conclusion: This ongoing study delineates a systematic cohort of genetic NDDs in the Indian subcontinent.
Keywords: Neurodevelopmental disorders, India, Genomic testing, Diagnosis, Mendelian disorder
Anju Shukla
Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
India
Purvi Majethia
Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
India
Michelle do Rosario
Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
India
Lakshmi Priya Rao
Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
India
Shruti Pande
Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
India
Karthik Nair
Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
India
Bhagesh Hunakunti
Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
India
Dhanya Lakshmi Narayanan
Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
India
Shrikiran Aroor
Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
India
Ramesh Bhat Y
Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
India
Leslie Lewis
Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
India
Suvasini Sharma
Lady Hardinge Medical College and Associated Kalawati Saran Children's Hospital, New Delhi, India
India
Praveen BK
Father Muller Medical College Hospital, Mangalore, India
India
Yatheesha BL
Dheemahi Child Neurology and Development center, Shimoga, Karnataka, India
India
SJ Patil
Narayana Hrudayalaya Hospitals/ Mazumdar-Shaw Medical Center, Bangalore, India
India
Nutan Kamath
Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, India
India
Sheela Nampoothiri
Amrita Institute of Medical Sciences & Research Centre, Cochin, India
India
Shruti Bajaj
The Purple Gene Clinic, Mumbai, India
India
Sankar V H
Department of Paediatrics, SAT Hospital, Govt. Medical College, Trivandrum, India
India
Kamalakshi G Bhat
Department of Paediatrics, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, India
India
Harsha Prasad
Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, India
India
Sunita Bijarnia-Mahay
Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India
India
Ratna Dua Puri
Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital, New Delhi, India
India
Hitesh Shah
Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
India
Rakshith Kedambadi
First Neuro Brain & Spine Super Speciality Hospital, Mangalore, India
India
Ali Kumble
Indiana Children Institute, Indiana Hospital, Mangalore, India
India
Santhosh Soans
A.J. Hospital and Research Centre, Mangalore, India
India
Vijay Kumar
Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
India
Naveen Sankhyan
Advanced Pediatrics Centre, Postgraduate Institute of Medical Education & Research, Chandigarh, India
India
Ravi K R
Narayana Multispecialty Clinic, Shimoga, Karnataka, India
India
Aparna Pai
Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
India
Dushyanth Babu Jasti
Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
India
Shahyan Siddiqui
STAR Institute of Neurosciences, STAR Hospitals, Hyderabad, India
India
Rajagopal Kadavigere
Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
India
M.L. Kulkarni
Jagadguru Jayadeva Muragharajendra (JJM) Medical College, Davangere, Karnataka, India
India
Katta Mohan Girisha
Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India
India
Stephanie Bielas
University of Michigan Medical School, Ann Arbor, Michigan, USA
United States
