Redcliffe Labs diagnoses India’s first case of DPH2-related Diphthamide Deficiency Syndrome-2

New Delhi: Redcliffe Labs has diagnosed the first known case of DPH2-related diphthamide deficiency syndrome-2 in India.

This groundbreaking diagnosis has been published in the prestigious Wiley American Journal of Medical Genetics Part A, marking a significant milestone in the field of medical genetics and broadening the clinical understanding of this rare genetic condition.

The diagnosis was carried out by Dr. Vykunta Raju K. N from Indira Gandhi Hospital, Bangalore, and Interpretation was done by Dr Himani Pandey, Lab Head of Genomics at Redcliffe Labs, and her team in collaboration with experts from leading medical institutions.

Identifying the DPH2 gene mutation enables healthcare providers to consider genetic counselling for families with a history of consanguinity. Early detection of this rare genetic disorder can facilitate timely intervention and management, potentially improving the quality of life for affected individuals. The ability to detect such mutations also aids in formulating more targeted and precise therapeutic strategies.

As per the diagnosis, the patient is a 1-year-9-month-old female who presented with a complex set of symptoms, including developmental delay, short stature, seizures, sparse hypopigmented hair, and dysmorphic facial features. Uniquely, the child also exhibited epileptic seizures, behavioural abnormalities, and neuroimaging findings such as cerebral atrophy and white matter hyperintensities – features not previously reported in other cases of this syndrome. The clinical picture also included developmental regression, autistic features, and hypotonia, making it a distinct and complex presentation.

The diagnosis was confirmed through whole-exome sequencing, which revealed a pathogenic nonsense variant (p.Arg477 *) in the DPH2 gene. This mutation truncates the DPH2 protein’s C-terminal, likely impacting its role in protein synthesis. According to the American College of Medical Genetics and Genomics (ACMG) standards, the identified variant has been classified as pathogenic. This is the first confirmed case of this syndrome in India and only the third reported case worldwide.

The patient exhibited delayed developmental milestones, including late attainment of neck control and the ability to sit with support, along with poor weight gain and feeding difficulties. Multiple episodes of generalized tonic seizures and epileptic spasms were documented, beginning at six months of age. Neuroimaging revealed cerebral atrophy, periventricular white matter hyperintensities, and prominent subarachnoid spaces, indicating significant neurological involvement. Additionally, the child showed distinct dysmorphic features such as a broad forehead with a high anterior hairline, sparse scalp hair, esotropia, a depressed nasal bridge, a bulbous nose, low-set ears, and brachydactyly in both hands and feet. This diagnosis holds immense significance for the medical community as it opens new avenues for preventive healthcare and prenatal diagnosis.

Dr. Himani Pandey, Lab Head Genomics of Redcliffe Labs said ,”This case exemplifies how integrative genomic approaches can elucidate the underlying molecular etiology of rare and clinically complex syndromes. Identifying a pathogenic DPH2 variant in an Indian patient not only contributes to the global repository of rare disease mutations but also enables more precise genotype-phenotype correlation. Such discoveries are vital to advancing personalized medicine, particularly in populations with high rates of consanguinity where recessive disorders often go undiagnosed.”

This discovery not only expands the known phenotypic spectrum of DPH2-related diphthamide deficiency syndrome-2 but also emphasizes the importance of including DPH2 mutations in diagnostic panels when evaluating developmental delays and epilepsy, particularly in populations with consanguineous backgrounds. Identifying this gene variant also paves the way for targeted research into the role of DPH2 in protein synthesis, potentially aiding in the development of therapeutic interventions.

Aditya, CEO & Founder of Redcliffe Labs, said,  “This diagnosis reflects our commitment to leveraging advanced genomic technologies to uncover rare and complex genetic disorders. Identifying the DPH2-related diphthamide deficiency syndrome-2 in India not only highlights the capabilities of our team but also sets a precedent for integrating precision genetics into routine diagnostics. Our focus remains on making genetic insights accessible and impactful for patient care.”