Rare Okur-Chung Neurodevelopmental Syndrome Diagnosed in Singapore Toddler via Whole Exome Sequencing
核心洞察
A three-year-old Singapore girl has been diagnosed with Okur-Chung neurodevelopmental syndrome (搜索) (OCNDS), a rare genetic condition identified only in 2016, making her one of just three known cases in the country.
The diagnosis was confirmed through trio whole exome sequencing at KK Women's and Children's Hospital (搜索), revealing a de novo mutation in the CSNK2A1 (搜索) gene with no inheritance from either parent.
OCNDS affects approximately one in every 100,000 people, with more than 370 patients diagnosed worldwide, and currently has no known curative treatment — management remains symptomatic with early intervention support.
A three-year-old Singapore girl has become one of only three known cases of Okur-Chung neurodevelopmental syndrome (搜索) (OCNDS) in the country, after a diagnostic odyssey that began when her mother noticed unusual head-shaking movements at seven months of age. The case illuminates both the challenges of diagnosing ultra-rare genetic conditions and the transformative role of advanced genomic sequencing in providing families with long-sought answers.
Tabitha, the middle child of Tiffany Tan and Joshua Lowe, was diagnosed by Dr. Nikki Fong, a geneticist at KK Women's and Children's Hospital (搜索) (KKH), following trio whole exome sequencing performed at 13 months of age. The test, which analyzes the protein-coding regions of DNA from the child and both parents, revealed a de novo — or spontaneous — mutation in the CSNK2A1 (搜索) gene.
"Individuals can have this condition as a result of an inherited variant, or a de novo change. Tabitha's was found to be de novo, as her parents did not carry this change. Therefore, the risk of it recurring in future offspring is predicted to be low," Dr. Fong told The Straits Times.
A Syndrome Newly Defined
OCNDS was first identified in 2016 by American geneticists Volkan Okur and Wendy Chung, with the inaugural paper published in the peer-reviewed journal Human Genetics that same year. The condition arises from alterations in the CSNK2A1 (搜索) gene, which encodes a protein critical for nervous system development.
According to Dr. Fong, individuals with OCNDS present with a spectrum of symptoms including global developmental delay, mild-to-moderate intellectual disability, decreased muscle tone, and behavioral issues such as aggression and tantrums. "They may also have different physical features from their peers, such as a smaller head and a short stature. Other clinical features include feeding difficulties in infancy, seizures and congenital heart abnormalities," she added.
The syndrome is estimated to affect approximately one in every 100,000 people, with more than 370 patients diagnosed worldwide. In Singapore, the other two known patients are in their teenage years.
The Diagnostic Journey
Tan first became concerned when Tabitha, then seven months old, exhibited persistent head-shaking. A pediatrician ruled out seizures, but broader developmental concerns persisted. "Tabitha was also physically smaller when she was born and was not hitting her milestones. For instance, she did not walk until she was two and she does not like milk," Tan recalled.
After relatives dismissed her concerns as excessive anxiety, Tan turned to her social network. "I started to doubt myself, but it was after I posted my concerns on my Instagram account that friends, who are in the healthcare industry, told me usually a mother's instinct is right, and that I should take her to a child development specialist," she said.
The specialist recommended developmental and genetic testing, though initial tests yielded no answers. "It was a long journey to get to the diagnosis. Tabitha went through several tests with no answers or signs of anything out of the ordinary until we managed to get a consultation with Dr. Nikki Fong," Tan said.
Clinical Management and Prognosis
Tabitha was first evaluated by the KKH genomics team at 10 months of age, enabling early access to intervention services and screening for comorbidities associated with OCNDS. "As she had feeding difficulties in infancy, she required interventions from the feeding clinic to ensure adequate nutrition and hydration," Dr. Fong noted.
Currently, there is no known disease-modifying treatment for OCNDS. "Management is symptomatic, with supportive treatment of medical issues and initiation of early intervention to support development of the child," Dr. Fong explained.
Tabitha's condition is classified as mild, though she continues to face challenges including speech delays and motor difficulties. She attends a mainstream preschool while receiving services through an Early Intervention Programme for Infants and Children (EIPIC) center, where she undergoes speech, occupational, and physical therapies alongside daily living skills training.
Dr. Fong emphasized the importance of ongoing surveillance: "She should also be reviewed to assess signs of feeding issues, new neurologic manifestations such as seizures and movement disorders, and be monitored for developmental progress, behavioral and educational needs."
Navigating an Uncertain Future
As Tabitha approaches school age, her family faces complex decisions about her educational pathway. "Her condition is mild... it is not severe enough for Special Education school. She also does not fit into mainstream, which will probably be too fast-paced for her and will become a real concern," Tan said. "The best choice would be to homeschool her. This way, I hope to be able to draw out her potential at her own pace."
A reassessment before school-going age will determine suitable schooling options and whether a deferment from primary school may be necessary.
The case underscores the growing clinical utility of whole exome sequencing in resolving cases of unexplained global developmental delay, particularly for ultra-rare conditions where traditional diagnostic approaches may fall short. For families like Tabitha's, a molecular diagnosis — even in the absence of a cure — can provide clarity, guide clinical management, and connect them with an emerging global community of affected individuals.