Mr Anand Menezes and his wife Suman with their daughters Atira (left) and Seana. The sisters are the world’s first known cases of Jamuar syndrome, a rare genetic abnormality that results in issues such as developmental delays, epileptic fits and speech impairment.PHOTO: COURTESY OF SUMAN MENEZES
When her daughter Atira was six months old, Mrs Suman Menezes realised that something was amiss.
She and her husband, Mr Anand Menezes, who are Indian nationals, noticed that Atira was unable to sit upright. Up until then, the girl had shown no signs of developmental delay and had hit all the milestones of a growing infant, such as rolling over on her back.
Things began to go downhill after. A month after her third birthday, Atira suffered her first of many seizures to come. At five, she finally learnt to walk, but with an unsteady gait that has persisted until today. Now 17, she is still unable to speak.
The couple's younger daughter, Seana, who was born in 2011, eight years after her sister, suffered from similar symptoms.
Doctors whom the couple spoke to were not able to pinpoint the sisters' condition because the symptoms they exhibited were not specific or unique to a certain illness, such as epilepsy.
The couple finally got their answer in 2018. This was about 15 years after their first child was born, and three years after both Atira and Seana were entered in a KK Women's and Children's Hospital (KKH) programme called Bridges, or Bringing Research Innovations for the Diagnosis of Genetic diseases in Singapore.
Their doctor, Dr Saumya Jamuar, a senior consultant of genetics service at KKH, had entered them in the programme, which is done in collaboration with genomic research institutes such as the Agency for Science, Technology and Research (A*Star).
The programme puts children suspected of having genetic diseases through a series of genetic tests to identify the condition they have.
Through a genetic test known as exome sequencing, Atira and Seana were found to be the first known cases in the world suffering from Jamuar syndrome, a rare form of genetic abnormality that results in developmental delays, epileptic fits, speech impairment and an unsteady gait.
The siblings' conditions were found to be caused by a variation in the UGDH gene, which was previously not associated with any genetic diseases in humans.
The genetic mutation was found to be linked with reduced brain development and recessive epileptic encephalopathy - a condition characterised by epileptic seizures and speech and developmental delays.
The research director of A*Star's Institute of Medical Biology, Dr Bruno Reversade, whose team established this finding in the laboratory, said the discovery could pave the way to finding new therapeutic targets for epilepsies.
Since the Menezes siblings were diagnosed with the condition, 36 more children worldwide - including affected siblings - have been identified with Jamuar syndrome, named after the sisters' doctor this January, when the finding was published in Nature Communications.
Dr Jamuar said that although the discovery has not changed the existing treatment and therapies for the Menezes sisters, it could have an impact on future treatment for children similar to Atira and Seana.
"We now know where to look in terms of designing strategies for treatment. We're not there yet, but that might be the next frontier."
For Mr Menezes, 47, who came to Singapore in 2010 and works in the field of information technology, knowing the diagnosis was a form of closure.
It was the same for Mrs Menezes, 42, who quit her job in 2006 as a medical and psychiatric counsellor to care for her two children. "It gave us psychological comfort, to know that there is a medical reason as to why our children had these symptoms," she said.
"As parents, we would have been very happy if there was a treatment or medication for our kids. But as this is a genetic disorder, I know we might not be able to see a treatment. But in the long run, if that is available, it would be a blessing."
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