The visit highlighted the growing international effort to better understand Nicolaides-Baraitser syndrome (NCBRS).
NCBRS is an ultra-rare, autosomal dominant genetic disorder, caused by pathogenic variants in the SMARCA2 gene. This gene encodes the core catalytic subunit of the SW1/SNF complex which regulates gene expression by chromatin remodelling, meaning disruptions can have widespread effects on development. First described in 1993 by paediatric neurologist Dr. Paola Nicolaides and clinical geneticist Dr. Michael Baritser at Great Ormond Street Hospital (GOSH), NCBRS was reported as ‘An unusual syndrome with mental retardation and sparse hair’. Today, there are more than 300 confirmed cases worldwide, with a broad clinical presentation including developmental delay, limited speech, microcephaly, distinct facial features, and often co-occurring with epilepsy.
Not-for-profits are instrumental to scientific research, especially in the rare disease community, which has long been underserved. NCBRS Worldwide Foundation is one such organisation advocating and providing resources for research in NCBRS, as well as promoting awareness and supporting families and carers of individuals affected by the condition. Since 2024, Dr Stephanie Efthymiou from UCL QS IoN has been on the scientific advisory board of the NCBRS Worldwide Foundation.
During their trip, journalist Deepa Fernandez and her daughter Maya, who lives with NCBRS, first visited Dr. Nicolaides at her clinic at the American Medical Centre in Cyprus, returning to the clinician who first identified the condition more than three decades ago. They then travelled to London, where they were welcomed into the Neurogenetics Laboratory at UCL. They met members of the team, toured the tissue culture facilities used to study patient-derived iPSC cells and discussed ongoing research into NCBRS carried out at the lab. The visit also included a walking tour of Great Ormond Street Hospital, offering a powerful historical perspective on how understanding of NCBRS has evolved since its first description over 30 years ago.
Looking ahead, the team led by Dr Stephanie Efthymiou (Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology) are pushing to identify the most frequently occurring SMARCA2 variants in patients, to inform their introduction into mouse models being developed. Plans are also underway to use patient derived cells lines from previous family gatherings to model the condition in vitro. In parallel, efforts are being made to build a patient registry, which stores detailed information about individuals affected by NCBRS, providing a centralised database for researchers and clinicians.
Together these efforts reflect a growing, collaborative approach to rare disease research, bringing together scientists, clinicians and families to accelerate progress. Certainly, there is growing hope for the NCBRS community as research at UCL continues to lay the foundations for improved understanding, diagnosis and, ultimately, the development of targeted therapies.
Prepared by Michelle Xu