Review
Cell Biology
Ana Quelle-Regaldie, Daniel Sobrido-Camean, Anton Barreiro-Iglesias, Maria Jesus Sobrido, Laura Sanchez
Summary: Zebrafish models play a crucial role in studying hereditary dominant ataxias, aiding in understanding disease phenotypes, gene functions, behaviors, and potential treatments. However, there is a current lack of adult zebrafish heterozygous models and knock-in models, highlighting the need for more accurate models using new genetic editing techniques in the future.
Review
Cell Biology
Ana Quelle-Regaldie, Daniel Sobrido-Camean, Anton Barreiro-Iglesias, Maria Jesus Sobrido, Laura Sanchez
Summary: Research on autosomal recessive ataxias is limited compared to autosomal dominant ataxias, but zebrafish models have proven to be valuable in uncovering potential treatments and studying the disease.
Article
Medicine, General & Internal
Ping Zhang, Jing-Yun Fu
Summary: Kallmann syndrome is a rare genetic disorder characterized by delayed puberty and infertility. This article reports a case of a 26-year-old male with the syndrome, who showed improvement in hormone levels after treatment with pulsatile GnRH subcutaneous therapy by pump.
WORLD JOURNAL OF CLINICAL CASES
(2022)
Review
Clinical Neurology
Marie Beaudin, Mario Manto, Jeremy D. Schmahmann, Massimo Pandolfo, Nicolas Dupre
Summary: In this Review, the authors discuss recessive ataxias with ganglionopathy or polyneuropathy, focusing on Friedreich ataxia and RFC1-associated cerebellar ataxia, neuropathy, vestibular areflexia syndrome. They explore the shared pathogenic mechanisms and therapeutic advances in these diseases. The Review also provides insights into the diagnostic challenges and clinical features of these diseases.
NATURE REVIEWS NEUROLOGY
(2022)
Review
Neurosciences
Ikhlass H. Salem, Marie Beaudin, Christopher J. Klein, Nicolas Dupre
Summary: Autosomal recessive cerebellar ataxias (ARCAs) are a group of neurodegenerative diseases characterized by cerebellar ataxia, dysmetria, dysarthria, and nystagmus that are inherited in an autosomal recessive fashion. The diagnosis of ARCAs is challenging due to low prevalence and overlapping clinical features. Treatment is mainly symptomatic, but new therapeutic approaches are being explored. Improved motor rehabilitation protocols and noninvasive cerebellar stimulation can delay disease progression, and gene and molecular targeting therapies show promise for repairing defective genes. This article provides an overview of current management and treatment strategies for ARCAs, with an emphasis on promising perspectives.
CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS
(2023)
Review
Clinical Neurology
Giulia Coarelli, Marie Coutelier, Alexandra Durr
Summary: Dominantly inherited spinocerebellar ataxias (SCAs) exhibit phenotypic variation and can be caused by multiple potentially pathogenic variants. Genome sequencing should be the preferred diagnostic tool due to the extreme clinical and genetic heterogeneity, but its availability is limited. Although treatments like riluzole and transcranial direct current stimulation have been tested, their efficacy remains conflicting. Biomarkers, such as neurofilament light chain and brain MRI, should be used to assess preataxic carriers and monitor target engagement by gene therapies.
Article
Endocrinology & Metabolism
Reema Habiby, Daniel G. Bichet, Marie-Francoise Arthus, Dervia Connaughton, Shirlee Shril, Shrikant Mane, Amar J. Majmundar, Friedhelm Hildebrandt, Gary L. Robertson
Summary: This study investigates a novel form of familial diabetes insipidus that is inherited in an X-linked recessive manner. It is caused by a deficiency in vasopressin and can be corrected with desmopressin therapy. The findings are important for the accurate diagnosis and management of this disease.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Review
Medicine, General & Internal
Judy Savige, Mary Huang, Marina Shenelli Croos Dabrera, Krushnam Shukla, Joel Gibson
Summary: Alport syndrome is a genetic disease caused by pathogenic variants in COL4A3 - COL4A5 genes, leading to kidney failure and hearing loss. Understanding the genotype-phenotype correlations can help predict the age of kidney failure and guide clinical management.
FRONTIERS IN MEDICINE
(2022)
Article
Clinical Neurology
Evgenii Nuzhnyi, Yury Seliverstov, Sergey Klyushnikov, Tatiana Krylova, Polina Tsygankova, Igor Bychkov, Ekaterina Zakharova, Rodion Konovalov, Pavel Fedin, Natalia Abramycheva, Sergey Illarioshkin
Summary: The study found that POLG-associated ataxias make up a significant proportion of adult recessive and sporadic ataxias in the Russian population, typically presenting with symptoms such as external ophthalmoparesis, cerebellar signs, and sensory neuropathy. Screening patients with specific clinical and neuroimaging features for common POLG mutations, followed by NGS panel testing, is recommended for better understanding of this disease. Thorough cognitive and neuropsychiatric profiling is needed in future clinical studies to complete the phenotype of POLG-related disorders.
CLINICAL NEUROLOGY AND NEUROSURGERY
(2021)
Article
Clinical Neurology
Andreas Thieme, Jennifer Faber, Patricia Sulzer, Kathrin Reetz, Imis Dogan, Miriam Barkhoff, Janna Krahe, Heike Jacobi, Julia-Elisabeth Aktories, Martina Minnerop, Saskia Elben, Raquel van der Veen, Johanna Mueller, Giorgi Batsikadze, Juergen Konczak, Matthis Synofzik, Sandra Roeske, Dagmar Timmann
Summary: This multicenter study tested the ability of the CCAS-Scale to diagnose CCAS in individual patients with common forms of hereditary ataxia. The results showed that the CCAS-Scale had limited ability to diagnose CCAS in individual patients, especially in milder cases with a substantial number of false-positive results. SCA3 patients performed the worst, with lower scores compared to SCA6 and FRDA patients.
JOURNAL OF NEUROLOGY
(2022)
Article
Genetics & Heredity
Michal Levy, Lily Bazak, Noa Lev-El, Rotem Greenberg, Nesia Kropach, Lina Basel-Salmon, Idit Maya
Summary: This study identifies three novel disease-causing variants in the COL4A4 gene that are recurrent among Jews of Bukharian ancestry and cause Alport syndrome in both dominant and recessive autosomal inheritance patterns.
Review
Neurosciences
Marios Hadjivassiliou, Mario Manto, Hiroshi Mitoma
Summary: The cerebellum is vulnerable to immune attacks and can be affected by various immune-mediated cerebellar ataxias (IMCAs). These conditions have diverse etiologies, presenting with different clinical features, with cerebellar ataxia being a main phenotype. Further research and diagnosis are needed to better understand primary autoimmune cerebellar ataxia (PACA).
Review
Ophthalmology
Asima Hassan, Yaser R. Mir, Raja A. H. Kuchay
Summary: The advent of new sequencing technologies and diagnostic procedures has facilitated a deeper understanding of previously unknown disorders. This has been achieved through the discovery of novel genes and variants, as well as advances in functional validation techniques. Animal models and gene editing tools have contributed to elucidating gene functions and improving diagnosis and treatment. This review provides a comprehensive overview of ocular and genetic findings in X-linked recessive disorders, which has not been done before.
INDIAN JOURNAL OF OPHTHALMOLOGY
(2022)
Review
Clinical Neurology
Nicole Urbini, Libera Siciliano, Giusy Olivito, Maria Leggio
Summary: This systematic review confirms the presence of autonomic dysfunctions in different genetic subtypes of spinocerebellar ataxias (SCAs), highlighting the role of the cerebellum in the autonomic nervous system (ANS). It emphasizes the importance of investigating these functions in clinical practice.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Chi-Ying R. Lin, Sheng-Han Kuo
Summary: A variety of etiologies can result in cerebellar dysfunction, causing ataxia symptoms. Accurately diagnosing the cause for cerebellar ataxia can be challenging, but step-wise investigations have revealed nutritional, toxin, immune-mediated, genetic, and degenerative disorders as underlying causes. Recent advances in genetics have identified new genes for both autosomal dominant and autosomal recessive ataxias, and new therapies targeting specific biological pathways are being explored. New diagnostic criteria, particularly for multiple system atrophy, will greatly impact future clinical research in ataxia. This article provides a comprehensive review of the symptoms, laboratory testing, neuroimaging, genetic testing, and management strategies for cerebellar ataxia, with a focus on recent advances.
SEMINARS IN NEUROLOGY
(2023)