SINGAPORE – The girl was 10 years old before she was finally able to say “papa” and “mama”, and feed herself using a spoon.
She was also smaller in stature compared with her peers, standing at 1.16m and weighing under 16kg.
For years, she was a medical mystery: Doctors could not explain what led to the significant delay in her developmental milestones.
The teenager, who has been seen by doctors from the KK Women’s and Children’s Hospital (KKH) since infancy, underwent the usual clinical investigations like blood tests and brain MRIs – all yielded no clear diagnosis.
But her symptoms gave them a clue as to where to look – in her genes, for a possible underlying rare genetic disorder.
Explaining why a delay in developmental milestones is often linked with genetic disorders, Associate Professor Tan Ee Shien, head and senior consultant at KKH’s genetics service, said: “When and how a child learns to walk, talk and develop social skills – these are all very much determined by the maturation of the brain.
“The development of the brain and all its neural connections is a complex process that involves many different genes and biological pathways. Therefore, when there is a genetic mutation, the brain is one key system that is affected.”
The girl was enrolled in a KKH programme called Bridges, or Bringing Research Innovations for the Diagnosis of Genetic Diseases.
The initiative was set up in 2014 to help children with suspected rare genetic disorders find a diagnosis.
Its work is done in collaboration with genomic research institutes such as the Agency for Science, Technology and Research.
Approximately 80 per cent of rare diseases are estimated to have a genetic origin.
In Singapore, a rare disease is defined as a condition that affects fewer than one in 2,000 individuals. Around 2,500 people here are estimated to have a rare disease.
The teenage girl turned out to be among them. Using a technique called whole exome sequencing, which allows for the identification of genetic variants across many genes in a single test, Bridges’ researchers saw mutations in the DRG1 gene.
Working with international researchers, Prof Tan was able to prove the effect of the disrupted DRG1 in patients.
An article on the newly discovered disease, named Tan-Almurshedi syndrome after Prof Tan and another researcher, was published in the Genetics In Medicine journal in 2023. Including the Singaporean patient, there are only four known cases in the world.
Tan-Almurshedi syndrome is one of five previously unknown genetic diseases discovered through the Bridges programme. The others were found between 2016 and 2020.
