Computer-aided Facial Analysis in Diagnosing Dysmorphic Syndromes in Indian Children

Objective: To assess the utility of computer-aided facial analysis in identifying dysmorphicsyndromes in Indian children. Methods: Fifty-one patients with a definite molecular orcytogenetic diagnosis and recognizable facial dysmorphism were enrolled in the study andtheir facial photographs were uploaded in the Face2Gene software. The results provided bythe software were compared with the molecular diagnosis. Results: Of the 51 patients, thesoftware predicted the correct diagnosis in 37 patients (72.5%); predicted as the first in thetop ten suggestions in 26 (70.2%). In 14 patients, the software did not suggest a correctdiagnosis. Conclusions: Computer-aided facial analysis is a method that can aid indiagnosis of genetic syndromes in Indian children. As more clinicians start to use thissoftware, its accuracy is expected to improve.

Molecular and Histopathological Characterization of Patients Presenting with the Duchenne Muscular Dystrophy Phenotype in a Tertiary Care Center in Southern India

Objective: To study the histopathological characteristics and mutation spectrum of patientspresenting with the Duchenne muscular dystrophy (DMD) phenotype. Methods: This wasa descriptive study conducted over a period of 8 years. Multiplex ligation-dependent probeamplification (MLPA) was done in patients presenting with the DMD phenotype. If MLPA wasnegative, patients were offered muscle biopsy for histopathological studies and/or nextgeneration sequencing (NGS) based multigene panel testing for muscular dystrophies.Results: Of the 510 patients included, mutation in the DMD gene was detected by MLPA in372 (72.9%), of whom 342 (67.1%) had exonic deletions and 30 (5.9%) had exonicduplications. Exons 45-55 were most commonly involved in large deletions and exons 1-10were the commonest exons involved in duplications. In the MLPA-negative cohort, 27proceeded for muscle biopsy. NGS was done in 14 patients, 10 of whom had pathogenicmutations in the DMD gene, 3 were non dystrophinopathies and no pathogenic variant couldbe identified in one patient. Conclusions: For patients presenting with the DMD phenotype,MLPA of the DMD gene has a high diagnostic rate of about 73%, and non-dystrophinopathies may constitute a small but significant proportion.

Aetiologic spectrum of mental retardation & developmental delay in India.

Background & objectives: The aetiology of mental retardation is varied and difficult to establish. Reports from India on the spectrum of underlying causative conditions are lacking. This retrospective study was conducted to establish the various aetiologies of mental retardation (MR) and developmental delay (DD) in patients attending a medical genetics centre in north India and to assess the contribution of genetic disorders. Methods: This retrospective study was conducted at a tertiary care centre in north India. All patients attending the centre with MR or DD from January 2007 to December 2009 were included. The aetiology of MR/DD was ascertained after clinical assessment and targeted laboratory evaluation. The spectrum of causative conditions and contribution of genetic disorders was established. Results: A total of 338 patients were included in the study, of whom definite diagnosis was established in 253 (74.8%). The various aetiological categories were: chromosomal disorders in 112 (33.1%), non chromosomal syndromes in 32 (9.5%), neurometabolic disorders in 34 (10.1%), central nervous system structural defects in 25 (7.4%), cerebral palsy in 43 (12.7%) and environmental insults in 7 (2%). Eighty five patients (25.2%) had idiopathic mental retardation. A total of 196 (58%) patients had a genetic disorder as the cause of MR/DD. Interpretation & conclusions: The aetiology of MR/DD is varied and difficult to establish in a significant proportion of patients. Chromosomal and various monogenic disorders contribute to a large number of MR/DD cases and hence a genetic work up is essential for all such patients.