Header

UZH-Logo

Maintenance Infos

Molecular Basis and Clinical Overview of McLeod Syndrome Compared With Other Neuroacanthocytosis Syndromes: A Review


Roulis, Eileen; Hyland, Catherine; Flower, Robert; Gassner, Christoph; Jung, Hans H; Frey, Beat M (2018). Molecular Basis and Clinical Overview of McLeod Syndrome Compared With Other Neuroacanthocytosis Syndromes: A Review. JAMA Neurology, 75(12):1554.

Abstract

Importance McLeod syndrome, encoded by the gene XK, is a rare and progressive disease that shares important similarities with Huntington disease but has widely varied neurologic, neuromuscular, and cardiologic manifestations. Patients with McLeod syndrome have a distinct hematologic presentation with specific transfusion requirements. Because of its X-linked location, loss of the XK gene or pathogenic variants in this gene are principally associated with the McLeod blood group phenotype in male patients. The clinical manifestation of McLeod syndrome results from allelic variants of the XK gene or as part of a contiguous gene deletion syndrome involving XK and adjacent genes, including those for chronic granulomatous disease, Duchenne muscular dystrophy, and retinitis pigmentosa. McLeod syndrome typically manifests as neurologic and cardiologic symptoms that evolve in individuals beginning at approximately 40 years of age.
Observations Diagnosis of McLeod syndrome encompasses a number of specialties, including neurology and transfusion medicine. However, information regarding the molecular basis of the syndrome is incomplete, and clinical information is difficult to find. The International Society of Blood Transfusion has recently compiled and curated a listing of XK alleles associated with the McLeod phenotype. Of note, McLeod syndrome caused by structural variants as well as those cases diagnosed as part of a contiguous gene deletion syndrome were previously classified under a singular allele designation.
Conclusions and Relevance This review discusses the clinical manifestations and molecular basis of McLeod syndrome and provides a comprehensive listing of alleles with involvement in the syndrome published to date. This review highlights the clinical diversity of McLeod syndrome and discusses the development of molecular tools to elucidate genetic causes of disease. A more precise and systematic genetic classification is the first step toward correlating and understanding the diverse phenotypic manifestations of McLeod syndrome and may guide clinical treatment of patients and support for affected and carrier family members. This review provides a knowledge base for neurologists, hematologists, and clinical geneticists on this rare and debilitating disease.

Abstract

Importance McLeod syndrome, encoded by the gene XK, is a rare and progressive disease that shares important similarities with Huntington disease but has widely varied neurologic, neuromuscular, and cardiologic manifestations. Patients with McLeod syndrome have a distinct hematologic presentation with specific transfusion requirements. Because of its X-linked location, loss of the XK gene or pathogenic variants in this gene are principally associated with the McLeod blood group phenotype in male patients. The clinical manifestation of McLeod syndrome results from allelic variants of the XK gene or as part of a contiguous gene deletion syndrome involving XK and adjacent genes, including those for chronic granulomatous disease, Duchenne muscular dystrophy, and retinitis pigmentosa. McLeod syndrome typically manifests as neurologic and cardiologic symptoms that evolve in individuals beginning at approximately 40 years of age.
Observations Diagnosis of McLeod syndrome encompasses a number of specialties, including neurology and transfusion medicine. However, information regarding the molecular basis of the syndrome is incomplete, and clinical information is difficult to find. The International Society of Blood Transfusion has recently compiled and curated a listing of XK alleles associated with the McLeod phenotype. Of note, McLeod syndrome caused by structural variants as well as those cases diagnosed as part of a contiguous gene deletion syndrome were previously classified under a singular allele designation.
Conclusions and Relevance This review discusses the clinical manifestations and molecular basis of McLeod syndrome and provides a comprehensive listing of alleles with involvement in the syndrome published to date. This review highlights the clinical diversity of McLeod syndrome and discusses the development of molecular tools to elucidate genetic causes of disease. A more precise and systematic genetic classification is the first step toward correlating and understanding the diverse phenotypic manifestations of McLeod syndrome and may guide clinical treatment of patients and support for affected and carrier family members. This review provides a knowledge base for neurologists, hematologists, and clinical geneticists on this rare and debilitating disease.

Statistics

Citations

Dimensions.ai Metrics
7 citations in Web of Science®
5 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

265 downloads since deposited on 23 Nov 2018
164 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurology
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:1 December 2018
Deposited On:23 Nov 2018 07:17
Last Modified:13 Oct 2019 05:52
Publisher:American Medical Association (AMA)
ISSN:2168-6149
OA Status:Green
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1001/jamaneurol.2018.2166
PubMed ID:30128557

Download

Green Open Access

Download PDF  'Molecular Basis and Clinical Overview of McLeod Syndrome Compared With Other Neuroacanthocytosis Syndromes: A Review'.
Preview
Content: Published Version
Filetype: PDF
Size: 1MB
View at publisher