Abstract
Potassium channels are a heterogeneous group of membrane-bound proteins, whose functions support a diverse range of biological processes. Genetic disorders arising from mutations in potassium channels are classically recognized by symptoms arising from acute channel dysfunction, such as periodic paralysis, ataxia, seizures, or cardiac conduction abnormalities, often in a patient with otherwise normal examination findings. In this chapter, we review a distinct subgroup of rare potassium channelopathies whose presentations are instead suggestive of a developmental disorder, with features including intellectual disability, craniofacial dysmorphism or other physical anomalies. Known conditions within this subgroup are: Andersen-Tawil syndrome, Birk-Barel syndrome, Cantú syndrome, Keppen-Lubinsky syndrome, Temple-Baraitser syndrome, Zimmerman-Laband syndrome and a very similar disorder called Bauer-Tartaglia or FHEIG syndrome. Ion channelopathies are unlikely to be routinely considered in the differential diagnosis of children presenting with developmental concerns, and so detailed description and photographs of the clinical phenotype are provided to aid recognition. For several of these disorders, functional characterization of the genetic mutations responsible has led to identification of candidate therapies, including drugs already commonly used for other indications, which adds further impetus to their prompt recognition. Together, these cases illustrate the potential for mechanistic insights gained from genetic diagnosis to drive translational work toward targeted, disease-modifying therapies for rare disorders.
Keywords:
Channelopathies; Dysmorphology; Potassium channels; Rare diseases; Translational medicine.
© 2020 Elsevier Inc. All rights reserved.
MeSH terms
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Abnormalities, Multiple / drug therapy
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Abnormalities, Multiple / genetics*
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Abnormalities, Multiple / pathology
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Abnormalities, Multiple / physiopathology
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Andersen Syndrome / drug therapy
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Andersen Syndrome / genetics*
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Andersen Syndrome / pathology
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Andersen Syndrome / physiopathology
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Cardiomegaly / drug therapy
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Cardiomegaly / genetics*
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Cardiomegaly / pathology
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Cardiomegaly / physiopathology
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Channelopathies / drug therapy
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Channelopathies / genetics*
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Channelopathies / metabolism
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Channelopathies / physiopathology
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Child
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Craniofacial Abnormalities / drug therapy
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Craniofacial Abnormalities / genetics*
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Craniofacial Abnormalities / pathology
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Craniofacial Abnormalities / physiopathology
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Fibromatosis, Gingival / drug therapy
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Fibromatosis, Gingival / genetics*
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Fibromatosis, Gingival / pathology
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Fibromatosis, Gingival / physiopathology
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Hallux / abnormalities*
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Hallux / pathology
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Hallux / physiopathology
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Hand Deformities, Congenital / drug therapy
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Hand Deformities, Congenital / genetics*
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Hand Deformities, Congenital / pathology
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Hand Deformities, Congenital / physiopathology
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Humans
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Hypertrichosis / drug therapy
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Hypertrichosis / genetics*
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Hypertrichosis / pathology
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Hypertrichosis / physiopathology
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Intellectual Disability / drug therapy
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Intellectual Disability / genetics*
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Intellectual Disability / pathology
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Intellectual Disability / physiopathology
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Muscle Hypotonia / drug therapy
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Muscle Hypotonia / genetics*
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Muscle Hypotonia / pathology
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Muscle Hypotonia / physiopathology
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Nails, Malformed / drug therapy
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Nails, Malformed / genetics*
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Nails, Malformed / pathology
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Nails, Malformed / physiopathology
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Osteochondrodysplasias / drug therapy
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Osteochondrodysplasias / genetics*
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Osteochondrodysplasias / pathology
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Osteochondrodysplasias / physiopathology
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Potassium Channels / genetics*
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Potassium Channels / metabolism
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Thumb / abnormalities*
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Thumb / pathology
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Thumb / physiopathology
Supplementary concepts
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Birk-Barel Mental Retardation Dysmorphism Syndrome
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Cantu syndrome
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Temple-Baraitser Syndrome
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Zimmerman Laband syndrome