Clinical, radiological and molecular studies in 24 individuals with Dyggve-Melchior-Clausen dysplasia and Smith-McCort dysplasia from India.

BACKGROUND: Dyggve-Melchior-Clausen dysplasia (DMC) and Smith-McCort dysplasia (SMC types 1 and 2) are rare spondyloepimetaphyseal dysplasias with identical radiological findings. The presence of intellectual disability in DMC and normal intellect in SMC differentiates the two. DMC and SMC1 are allelic and caused by homozygous or compound heterozygous variants in DYM. SMC2 is caused by variations in RAB33B. Both DYM and RAB33B are important in intravesicular transport and function in the Golgi apparatus. METHODS: Detailed clinical phenotyping and skeletal radiography followed by molecular testing were performed in all affected individuals. Next-generation sequencing and Sanger sequencing were used to confirm DYM and RAB33B variants. Sanger sequencing of familial variants was done in all parents. RESULTS: 24 affected individuals from seven centres are described. 18 had DMC and 6 had SMC2. Parental consanguinity was present in 15 of 19 (79%). Height <3 SD and gait abnormalities were seen in 20 and 14 individuals, respectively. The characteristic radiological findings of lacy iliac crests and double-humped vertebral bodies were seen in 96% and 88% of the affected. Radiological findings became attenuated with age. 23 individuals harboured biallelic variants in either DYM or RAB33B. Fourteen different variants were identified, out of which 10 were novel. The most frequently occurring variants in this group were c.719 C>A (3), c.1488_1489del (2), c.1484dup (2) and c.1563+2T>C (2) in DYM and c.400C>T (2) and c.186del (2) in RAB33B. The majority of these have not been reported previously. CONCLUSION: This large cohort from India contributes to the increasing knowledge of clinical and molecular findings in these rare 'Golgipathies'.

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.