Each month, we share summaries of recent Rare Diseases Clinical Research Network (RDCRN) grant-funded publications. Catch up on the latest RDCRN research below.
Jump to:
- Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN)
- Spastic Paraplegia Centers of Excellence Research Network (SP-CERN)
Listen to these summaries on the Rare Research Report podcast.
Global Leukodystrophy Initiative Clinical Trials Network (GLIA-CTN)
Investigating Language Skills in Children with Alexander Disease
Alexander disease is a rare disorder of the nervous system characterized as a leukodystrophy, a group of disorders affecting the myelin (the fatty coating surrounding nerve fibers). People with Alexander disease may have trouble walking, speaking, and swallowing.
In this study, researchers investigated the relationship between disease characteristics, age, and language skills in patients with Alexander disease. First, the team used clinical and imaging features to determine disease subtypes—including cerebral, intermediate, and bulbospinal—among 82 participants. Next, they used developmentally appropriate tests to assess participants' language and functional communication abilities. Then, they used statistical methods to find differences across groups.
Results showed that overall, cerebral patients experienced the most significant language deficits compared to intermediate and bulbospinal patients. Authors note that these findings can be used to better understand the impact of communication deficits and to provide accommodations and interventions in treatment plans for patients with Alexander disease.
Levin D, Levin J, Joung J, Liu GW, Donaher J, Faig W, Waldman AT. Language Skills in Patients With Alexander Disease. Am J Speech Lang Pathol. 2026 Jan 13;35(1):211-225. doi: 10.1044/2025_AJSLP-25-00185. Epub 2025 Nov 18. PMID: 41253129; PMCID: PMC12805811.
Spastic Paraplegia Centers of Excellence Research Network (SP-CERN)
Evaluating the Use of Genome Sequencing in Diagnosing Children with Progressive Movement Disorders
Childhood-onset movement disorders have a large range of symptoms and genetic causes. Over 500 different genes are associated with these disorders. However, standard genetic testing may not detect some of the genetic variants.
In this study, researchers evaluated the use of genome sequencing in diagnosing children with progressive movement disorders. First, the team used whole genome sequencing to identify variants in 100 children and young adults with early-onset progressive movement disorders and prior nondiagnostic testing. Then, a multidisciplinary team interpreted the variants and matched them with different phenotypes.
Results included a molecular diagnosis in 27% of cases, with candidate variants identified in an additional 33%. Short-read whole genome sequencing showed a small increase in diagnoses over exome sequencing. Most of the diagnoses were achieved through reanalysis of exome-level data. Authors note that these findings highlight the importance of repeat variant interpretation and the need for improved analytic pipelines to fully realize the potential of genome sequencing.
Schierbaum L, Gonzalez Saez-Diez E, Tam A, Rong J, Zubair U, Bernardi K, Yang K, Quiroz V, Zaman Z, Saffari A, Carty S, Agianda HAP, Alexandrescu S, Eichler F, Sveden A, Chopra M, Calame DG, Danzi MC, Zuchner S, Ebrahimi-Fakhari D. Diagnostic yield of genome sequencing in children with progressive movement disorders. Brain. 2026 Feb 5:awag050. doi: 10.1093/brain/awag050. Epub ahead of print. PMID: 41640354.
The Rare Diseases Clinical Research Network (RDCRN) is funded by the National Institutes of Health (NIH) and led by the National Center for Advancing Translational Sciences (NCATS) through its Division of Rare Diseases Research Innovation (DRDRI). Now in its fifth five-year funding cycle, RDCRN is a partnership with funding and programmatic support provided by Institutes, Centers, and Offices across NIH, including the National Institute of Neurological Disorders and Stroke, the National Institute of Allergy and Infectious Diseases, the National Institute of Diabetes and Digestive and Kidney Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Heart, Lung, and Blood Institute, the National Institute of Dental and Craniofacial Research, the National Institute of Mental Health, the Office of Dietary Supplements, the National Institute on Aging, the National Human Genome Research Institute, the National Institute on Deafness and Other Communication Disorders, and the Office of Research on Women’s Health.
