Related Experiment Video
Updated: Jun 27, 2026
07:59
Functional Characterization of Endogenously Expressed Human RYR1 Variants
Published on: June 9, 2021
Expanding the Phenotypic Spectrum of Raynaud-Claes Syndrome: A Rett-like Presentation with Two New Cases
Roberta Milone1, Alessandro Orsini2, Gemma Marinella1
1Department of Developmental Neuroscience, IRCCS Fondazione Stella Maris, 56128 Pisa, Italy.
Genes
|June 26, 2026
Summary
Pathogenic variants in the CLCN4 gene cause Raynaud-Claes syndrome, a rare X-linked neurodevelopmental disorder. This study reviews CLCN4 disorders and suggests a Rett-like classification for improved diagnosis and care.
Area of Science:
- Genetics
- Neuroscience
- Rare Diseases
Background:
- CLCN4 gene variants are linked to Raynaud-Claes syndrome, an X-linked neurodevelopmental disorder.
- Clinical presentation of CLCN4-related disorders is heterogeneous, with variable severity in females.
- Existing knowledge on CLCN4 neurodevelopmental disorders requires comprehensive review and case study analysis.
Purpose of the Study:
- To review current knowledge on CLCN4-related neurodevelopmental disorders.
- To describe two new patients (one male, one female) with pathogenic CLCN4 variants.
- To propose a reclassification of Raynaud-Claes syndrome as a Rett-like condition.
Main Methods:
- Literature review of CLCN4-related neurodevelopmental disorders.
- Clinical data collection and analysis of two novel patients with CLCN4 variants.
- Phenotypic comparison of new patients with previously reported cases.
Main Results:
- Two de novo pathogenic CLCN4 variants were identified in a female (c.2152C > T) and a male patient (c.949G > A).
- Phenotypic data from these patients were compared with existing literature, revealing similarities and differences.
- The review and case data support considering Raynaud-Claes syndrome as a Rett-like condition.
Conclusions:
- CLCN4-related neurodevelopmental disorders exhibit significant heterogeneity.
- Classifying Raynaud-Claes syndrome as Rett-like aids differential diagnosis and management.
- Multidisciplinary, longitudinal evaluation is crucial for optimizing patient care and genetic counseling.
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