KBG Syndrome in 16 Indian Individuals.

We aimed to describe the clinical and genetic characteristics of 16 individuals with KBG syndrome (KBGS) from 13 Indian families. We retrospectively analyzed the clinical details of individuals with KBGS harboring a likely pathogenic/pathogenic variant in ANKRD11. We also analyzed their facial gestalt using Face2Gene and recorded the top three differential disorders suggested by the application. The most frequent clinical features observed in our cohort were as follows: learning and intellectual disability-14/15 (93%), skeletal abnormalities-14/15 (93%), postnatal short stature-13/15 (87%), brachydactyly-11/15 (73%), and characteristic facial appearance-13/15 (87%). We identified 12 single nucleotide variants (SNVs), including six recurrent and six novel variants, and a copy number variant in the 16q24.3 region encompassing ANKRD11 gene. The novel variants were as follows: p.(Gln1236Ter), p.(Asp884ThrfsTer93), p.(Arg1466GlyfsTer87), p.(Tyr2056Ter), p.(Leu955TrpfsTer22), and p.(Lys766ArgfsTer10). The identified SNVs in ANKRD11 clustered around exon 9. We observed a high concordance of Face2Gene in predicting KBGS.

Telegenetics: The experience of an Indian center (Centre for Human Genetics) during the COVID-19 pandemic.

Because of the lockdowns and restrictions placed on non-emergency medical services due to the COVID-19 pandemic, we were prompted to set up telegenetic services for patients and families with genetic disorders. Genetic medicine poses special challenges because the unit of consultation and counseling is often the family and not just the individual. We describe here our experience over eight months in 2020 in evaluating 539 families with genetic disorders on a virtual platform. Patients from urban and rural districts of Karnataka and neighboring states received telegenetic consultation. Families were phoned by genetic counselors 14-28 days after the initial consultation to measure feedback. One member of each family was invited to complete a modified 9-item Telehealth Satisfaction Scale (TeSS scale). Of 293 respondents, approximately 87.3% reported satisfaction with the visual and audio quality of online contact and 86.7% on saving travel time and expenses. A shorter waiting time for appointments as compared to in-person appointments in the previous year was seen in approximately 90%. Nearly 87% reported satisfaction with online genetic consultation; however, 74% of these indicated a preference for a face-to-face appointment. The reasons for this included a cultural perception of confidence instilled by meeting medical specialists in person. Telegenetics presents unusual advantages in India because of the high usage of smartphones, unlimited Internet data as a feature of most Internet plans, free web-based video applications, and digital payments. We suggest that telegenetics may be an alternative in providing a hybrid model of care in non-emergency situations especially where resources are limited.

Molecular and clinical profiling in a large cohort of Asian Indians with glycogen storage disorders.

Glycogen storage disorders occur due to enzyme deficiencies in the glycogenolysis and gluconeogenesis pathway, encoded by 26 genes. GSD's present with overlapping phenotypes with variable severity. In this series, 57 individuals were molecularly confirmed for 7 GSD subtypes and their demographic data, clinical profiles and genotype-phenotype co-relations are studied. Genomic DNA from venous blood samples was isolated from clinically affected individuals. Targeted gene panel sequencing covering 23 genes and Sanger sequencing were employed. Various bioinformatic tools were used to predict pathogenicity for new variations. Close parental consanguinity was seen in 76%. Forty-nine pathogenic variations were detected of which 27 were novel. Variations were spread across GSDIa, Ib, III, VI, IXa, b and c. The largest subgroup was GSDIII in 28 individuals with 24 variations (12 novel) in AGL. The 1620+1G>C intronic variation was observed in 5 with GSDVI (PYGL). A total of eleven GSDIX are described with the first Indian report of type IXb. This is the largest study of GSDs from India. High levels of consanguinity in the local population and employment of targeted sequencing panels accounted for the range of GSDs reported here.

Case Series of Creatine Deficiency Syndrome due to Guanidinoacetate Methyltransferase Deficiency.

Guanidinoacetate methyltransferase (GAMT) deficiency is the second most common defect in the creatine metabolism pathway resulting in cerebral creatine deficiency syndrome (CCDS). We report three patients from two unrelated families, diagnosed with GAMT deficiency on next-generation sequencing. All the probands had happy predisposition as a predominant manifestation in addition to the reported features of global developmental delay, seizures, and microcephaly. This further expands the phenotype of CCDS. The workup for creatine deficiency disorder should be included in the diagnostic algorithm for children with nonsyndromic intellectual disability, especially in those with a happy demeanor. These cases exemplify the utility of magnetic resonance spectroscopy of the brain in the workup of nonsyndromic intellectual disability to diagnose a potentially treatable disorder. In addition, documentation of low serum creatinine may be supportive. Early diagnosis and treatment is essential for better prognosis.