A rare disease collaboration has stepped into the spotlight at the 2026 American College of Medical Genetics and Genomics (ACMG) meeting, which took place March 11-13 in Baltimore, where a partnership focused on Coffin-Lowry Syndrome (CLS) showed tangible progress and future therapeutic potential.
CureNDD, BioLogic Pharma Solutions, and Northwestern University Feinberg School of Medicine came together around a shared goal: to prepare for future clinical trials with a rare disorder through a structured natural history and patient registry effort.
Their poster, “Building a Natural History and Patient Registry Platform for Coffin-Lowry Syndrome (CLS): A Roadmap for Therapeutic Readiness,” describes a roadmap that begins with existing real-world data and builds toward a scalable, multi-stakeholder registry framework.
“Cure NDD–the Consortium Understanding, Research, and Education for X-linked Neurodevelopmental Disorders–was founded on the belief that rare disease progress requires alignment across academia, industry, and patient communities. This partnership demonstrates how multistakeholder engagements can transform uncertainty into meaningful differences for patients,” says Dr. Jin Lee, Founding Board Member of Cure NDD.
“For families living with Coffin-Lowry Syndrome, a comprehensive natural history effort does more than collect data—it gives structure to that uncertainty. By understanding disease trajectory and meaningful outcomes, we can ensure that future trials measure what truly matters to CLS patients.”
By analyzing disparate datasets and defining priority data elements, the team aims to capture how CLS unfolds over time, what daily life looks like for affected individuals, and which clinical endpoints will matter most when therapies move into human studies.
Understanding Coffin-Lowry Syndrome’s Unmet Needs
Coffin-Lowry Syndrome (CLS) is a rare X-linked neurodevelopmental disorder caused by pathogenic variants in the RPS6KA3 gene. It is typically characterized by significant intellectual disability, distinctive craniofacial and skeletal features, sensorineural hearing loss, and sleep issues. Despite its complex clinical picture, there are currently no approved therapies specifically targeting the underlying biology of CLS.
The poster of CureNDD, BioLogic Pharma Solutions, and Northwestern University noted that the limited natural history and the absence of a dedicated Coffin-Lowry–specific registry have constrained progress toward “therapeutic readiness,” a state in which a condition is well enough understood to support early-phase clinical trial design and regulatory dialogue.
For many families, the journey is filled with uncertainty: limited longitudinal data, fragmented genotype–phenotype information, and a lack of standardized outcome measures make it difficult to predict disease course or evaluate potential interventions.
Overview: An Advocacy-Driven Collaboration Around Data
A central component of the study involves analyzing deidentified data from several key sources: GeneDx, the Coffin-Lowry Syndrome Foundation, and the Coordination of Rare Diseases at Sanford (CoRDS) rare disease registry. Together, these sources capture complementary pieces of the Coffin-Lowry story, from genetic testing results and clinical features to registry-based and patient-reported information. By triangulating these findings, the team is beginning to assemble a more complete picture of the current Coffin-Lowry population.
Early analysis of integrated data underscores the extent to which the condition affects day-to-day functioning. Foundational de-identified demographic and clinical information from patients in the CoRDS registry shows that many individuals experience delays in developmental milestones, such as using the bathroom unassisted, dressing independently, and performing basic fine-motor tasks.
In several areas, the average age at which CLS patients achieve these milestones exceeds the typical upper limit for neurotypical peers, reflecting the neurodevelopmental burden of the condition.
“These data describing meaningful developmental milestones are impactful for patients and families impacted by CLS,” says Dr. Lauren Beach, Assistant Professor in the Department of Medical Social Sciences in the Northwestern University Feinberg School of Medicine.
“Studies that go beyond the traditional medical model of reporting deficit-based clinical symptoms and extend into offering evidence-based insights about what individuals with CLS can do are critically important.”
The data also highlight a substantial reliance on specialized care and support services. According to the data, 74% of patients in the analyzed cohort require specialty care, and at least half receive occupational therapy. More than half of individuals with CLS attend public schools, while roughly one-third attend special needs schools, underscoring both the heterogeneity of the condition and the need for tailored educational and support planning.
What the Roadmap Means for Patients and the Field
As the team shared its progress with peers at the 2026 ACMG, the collaboration outlined plans to move from data aggregation to a longitudinal, patient-centered research platform that can support interventional studies.
Planned work includes partnering with a third-party digital platform to consolidate medical records and use artificial intelligence and speech capabilities to track symptom trajectories and health outcomes in real time. The framework envisions both in-person and remote follow-up, with digital diaries to capture high-burden features between visits, thereby reducing logistical strain on families while enriching the dataset.
Mary Hames from BioLogic Pharma Solutions commented: “It’s exciting to work alongside academia and advocacy on a rare disease with significant unmet medical need. We’ve just started collecting CLS data, and the analysis is proving very informative.”
The team’s work is beginning to attract interest in the biotech industry. Roma Biosciences Inc has turned its attention to CLS and other X-linked neurodevelopmental disorders, exploring potential preclinical programs that may one day feed into clinical development.
Roma Biosciences’ interest serves as an early signal that the field is shifting from purely descriptive work to translational possibilities. For families, clinicians, and researchers invested in CLS, the work on display marks a foundation—one in which therapeutic readiness is no longer an aspiration, but an active, evolving reality.
The team anticipates that the work presented at ACMG 2026 will mark the beginning of a broader, sustained research effort and open the door to further collaboration on Coffin-Lowry Syndrome and other X-linked neurodevelopmental disorders.
