"Electrifying dysmorphology": Potassium channelopathies causing dysmorphic syndromes.

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.

CDK13-related disorder.

Mutations in CDK13 have recently been identified as a novel cause of syndromic intellectual disability. In this chapter, we review the 44 cases of CDK13-related disorder reported to date, highlighting key clinical pointers to this diagnosis including characteristic craniofacial features, feeding difficulties in infancy, and the presence of structural heart or brain malformations. The spectrum of reported mutations is also described, demonstrating an excess of missense mutations arising in the protein kinase domain.

Growing up with spinal muscular atrophy with respiratory distress (SMARD1).

Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is an inherited neuromuscular condition resulting from recessive mutations in the immunoglobulin mu-binding protein (IGHMBP2) gene. Affected individuals characteristically present in infancy with progressive distal weakness and respiratory distress secondary to diaphragmatic weakness. Considerable clinical heterogeneity has been described both in its presentation and phenotype in childhood; however little data pertaining to phenotype in adulthood have been reported to date.