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Anomalías Múltiples , Cara , Deformidades Congénitas de la Mano , Discapacidad Intelectual , Micrognatismo , Uñas Malformadas , Humanos , Anomalías Múltiples/genética , Anomalías Múltiples/patología , Uñas Malformadas/genética , Uñas Malformadas/congénito , Uñas Malformadas/patología , Micrognatismo/genética , Micrognatismo/etiología , Cara/anomalías , Deformidades Congénitas de la Mano/genética , Cuello/anomalías , Cuello/patología , Masculino , Dedos/anomalías , FemeninoAsunto(s)
Uñas Malformadas , Humanos , Uñas Malformadas/patología , Uñas/patología , Masculino , FemeninoRESUMEN
ABSTRACT: Onychocytic matricoma (OCM) is a benign neoplasm of the nail matrix. Only 18 cases of this tumor have been reported in the literature to date. We retrospectively analyzed the clinical features of 14 patients with OCM. The most common clinical feature was longitudinal xanthopachyonychia (n = 9), followed by longitudinal leukopachyonychia (=3) and longitudinal pachymelanonychia (n = 2). The most common clinical findings identified following dermoscopy and analysis at high magnification of classical photographs were free-edge thickening of the nail plate without pitting (n = 14), longitudinal ridging (n = 7), round white clods (n = 7), white dots (n = 7), and filiform hemorrhages (n = 7), followed by oval and linear white clods (n = 5), fuzzy lateral border (n = 5), and red-purple blood clods (n = 3). Nail clipping histopathology showed a thickened nail plate with multiple, small, round-to-oval spaces. The tumor expressed immunopositivity for LEF-1. Dermoscopy of the nail plate and nail clipping histology provides useful information with regards to the differential diagnosis with subungual squamous cell carcinoma and nail melanoma. Ex vivo-in vivo correlation facilitates a better dermoscopic assessment of this unique underrecognized disease. However, the differential diagnosis between OCM and onychocytic carcinoma requires biopsy of the tumor. LEF-1 as an onychogenic marker can be used to resolve the differential diagnosis between OCM and subungual longitudinal acanthoma/seborrheic keratosis.
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Acantoma , Carcinoma de Células Escamosas , Enfermedades de la Uña , Uñas Malformadas , Neoplasias Cutáneas , Humanos , Neoplasias Cutáneas/patología , Estudios Retrospectivos , Enfermedades de la Uña/diagnóstico , Enfermedades de la Uña/patología , Acantoma/patología , Uñas Malformadas/patología , Carcinoma de Células Escamosas/diagnóstico , Diagnóstico Diferencial , DermoscopíaRESUMEN
Nail disorders are often difficult to recognize and diagnose because of the subtlety of their presentation and their shared overlapping features that are common to several conditions. Experientially, this is further complicated by the fact that specific training on diagnosis of nail pathologies varies substantially across most residency programs and for a majority of medical and surgical specialties. To distinguish these presentations from true, potentially deleterious nail disorders, clinicians should have familiarity with the most commonly occurring nail pathologies and their associations, and use a systematic approach when examining or evaluating alterations in the nails. In the present study, we review the most common clinical disorders affecting the nail apparatus.
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Enfermedades de la Uña , Uñas Malformadas , Humanos , Uñas/patología , Enfermedades de la Uña/diagnóstico , Uñas Malformadas/diagnóstico , Uñas Malformadas/patologíaRESUMEN
BACKGROUND: Nail involvement in subepidermal autoimmune blistering diseases (SEABD) is not common. Although these changes can be transient, permanent changes can also occur. This study addresses nail involvement manifestations and their associated factors in patients with SEABD. METHODS: From March 2020 to March 2021, we enrolled 56 patients with SEABD who were being examined at a tertiary skin hospital and checked their nail changes. We investigated the association between the SEABD subtypes and treatments that patients were receiving and the nail abnormalities. Additional factors including age, gender, duration since diagnosis, presence of mucosal involvement, and anti-bp230 and anti-bp180 IgG antibody quantitative levels (in those patients with bullous pemphigoid) were analyzed. RESULTS: The most common nail abnormalities were ridging, onycholysis, and onychoschizia. We observed a lower prevalence of onycholysis in EBA, a lower prevalence of periungual bullae in MMP, and a higher prevalence of scarring loss in EBA. Rituximab and dapsone were effective in preventing onycholysis as well as prednisolone in preventing subungual hematoma. Multiple lesions were found to be more common in the foot digits including great toes, probably because of higher exposure to trauma. CONCLUSIONS: In summary, in patients with SEABD and concomitant nail involvement, the underlying disease control, proper treatment, and avoidance of trauma may be helpful.
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Uñas Malformadas , Onicólisis , Humanos , Estudios Transversales , Onicólisis/patología , Autoantígenos , Piel/patología , Uñas Malformadas/patología , AutoanticuerposAsunto(s)
Condroma/diagnóstico , Uñas Malformadas/etiología , Neoplasias Cutáneas/diagnóstico , Condroma/complicaciones , Condroma/patología , Condroma/cirugía , Dedos , Humanos , Masculino , Persona de Mediana Edad , Uñas/diagnóstico por imagen , Uñas/patología , Uñas/cirugía , Uñas Malformadas/diagnóstico , Uñas Malformadas/patología , Uñas Malformadas/cirugía , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugía , Resultado del TratamientoRESUMEN
The investigation of genetic forms of juvenile neurodegeneration could shed light on the causative mechanisms of neuronal loss. Schinzel-Giedion syndrome (SGS) is a fatal developmental syndrome caused by mutations in the SETBP1 gene, inducing the accumulation of its protein product. SGS features multi-organ involvement with severe intellectual and physical deficits due, at least in part, to early neurodegeneration. Here we introduce a human SGS model that displays disease-relevant phenotypes. We show that SGS neural progenitors exhibit aberrant proliferation, deregulation of oncogenes and suppressors, unresolved DNA damage, and resistance to apoptosis. Mechanistically, we demonstrate that high SETBP1 levels inhibit P53 function through the stabilization of SET, which in turn hinders P53 acetylation. We find that the inheritance of unresolved DNA damage in SGS neurons triggers the neurodegenerative process that can be alleviated either by PARP-1 inhibition or by NAD + supplementation. These results implicate that neuronal death in SGS originates from developmental alterations mainly in safeguarding cell identity and homeostasis.
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Anomalías Múltiples/patología , Proteínas Portadoras/metabolismo , Anomalías Craneofaciales/patología , Daño del ADN , Deformidades Congénitas de la Mano/patología , Trastornos Heredodegenerativos del Sistema Nervioso/patología , Discapacidad Intelectual/patología , Mutación , Uñas Malformadas/patología , Células-Madre Neurales/patología , Proteínas Nucleares/metabolismo , Proteína p53 Supresora de Tumor/antagonistas & inhibidores , Anomalías Múltiples/genética , Anomalías Múltiples/metabolismo , Proteínas Portadoras/genética , Células Cultivadas , Anomalías Craneofaciales/genética , Anomalías Craneofaciales/metabolismo , Deformidades Congénitas de la Mano/genética , Deformidades Congénitas de la Mano/metabolismo , Trastornos Heredodegenerativos del Sistema Nervioso/genética , Trastornos Heredodegenerativos del Sistema Nervioso/metabolismo , Humanos , Discapacidad Intelectual/genética , Discapacidad Intelectual/metabolismo , Uñas Malformadas/genética , Uñas Malformadas/metabolismo , Células-Madre Neurales/metabolismo , Proteínas Nucleares/genética , OrganoidesRESUMEN
ABSTRACT: Terry nails and Lindsay nails are similar forms of proximal apparent leukonychia (PAL). A change in nail bed vascularity is thought to be responsible for PAL. The study was aimed at investigating the frequency of PAL in patients attending a liver disease clinic, the factors associated with its presence, its value for detecting cirrhosis, its prognostic value for mortality, and associated capillaroscopic findings.A total of 521 patients were included (age range, 18-94âyears; 69% men). Systematic nail photographs were evaluated by 2 independent investigators. Disease-related data were obtained from the medical records. Mortality was evaluated after 7âyears of follow-up. Nailfold capillaroscopy was performed on a subset of 80 patients.PAL was present in 228 patients (43.8%; Terry nails in 205, Lindsay nails in 20, and both in 3). The kappa-coefficient of interobserver agreement was 0.82. The presence of PAL was associated with cirrhosis and, accordingly, with portal hypertension and hepatocellular dysfunction. The positive likelihood ratio of PAL for the diagnosis of cirrhosis was 1.6 (95% CI 1.3-1.92). PAL was independently associated with chronic alcohol abuse and was not a significant predictor of mortality. Venous loop dilatation and prominence of the venous plexus were observed on capillaroscopy in patients with cirrhosis but were not significantly associated with PAL.In summary, PAL is a common finding in patients from a liver clinic; it is associated with liver cirrhosis and with alcohol abuse. PAL is not associated with specific capillaroscopic findings. We propose the generic term proximal apparent leukonychia instead of classic eponymous titles to avoid confusion in the literature.
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Hipopigmentación/diagnóstico , Cirrosis Hepática/diagnóstico , Hepatopatías/patología , Angioscopía Microscópica/métodos , Enfermedades de la Uña/congénito , Adulto , Anciano , Alcoholismo/complicaciones , Capilares/patología , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Hipopigmentación/etiología , Cirrosis Hepática/mortalidad , Hepatopatías/complicaciones , Masculino , Angioscopía Microscópica/estadística & datos numéricos , Persona de Mediana Edad , Enfermedades de la Uña/diagnóstico , Enfermedades de la Uña/etiología , Uñas/irrigación sanguínea , Uñas Malformadas/diagnóstico , Uñas Malformadas/patología , Fotograbar/métodos , PronósticoRESUMEN
This study aimed to identify the molecular genetic etiology of an 8-year-old boy with amelogenesis imperfecta in permanent dentition. Bilateral cochlear implants were placed due to sensorineural hearing loss, and there was no other family member with a similar phenotype. Peripheral blood samples were collected with the understanding and written consent of the participating family members. A constitutional chromosome study was performed for the proband. Genomic DNA was isolated, and whole exome sequencing was performed. A series of bioinformatic analyses were performed with the obtained paired-end sequencing reads, and the variants were filtered and annotated with dbSNP147. There was no abnormality in the constitutional chromosome study. Whole exome sequencing analysis with trio samples identified a homozygous mutation (c.506T>C, p. (Leu169Pro)) in the PEX26 gene. We verified "temperature sensitivity (ts)" of patient-derived Pex26-L169P by expression in pex26 CHO mutant ZP167 cells to determine the effect of the L169P mutation on Pex26 function. The L169P mutation causes a mild ts-cellular phenotype representing the decreased peroxisomal import of catalase. This study supports the finding that the recessive mutations in PEX26 are associated with Heimler syndrome and demonstrates the importance of an early and correct diagnosis.
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Amelogénesis Imperfecta/genética , Pérdida Auditiva Sensorineural/genética , Proteínas de la Membrana/genética , Uñas Malformadas/genética , Amelogénesis Imperfecta/patología , Animales , Células CHO , Niño , Cricetinae , Cricetulus , Pérdida Auditiva Sensorineural/patología , Homocigoto , Humanos , Masculino , Proteínas de la Membrana/metabolismo , Mutación , Uñas Malformadas/patología , Fenotipo , Transporte de ProteínasRESUMEN
Hereditary leukonychia (HL) is a rare nail dystrophy disease, and several different clinical manifestations and mutations in the phospholipase C δ 1 (PLCD1) gene have been reported. The present study reports on one Chinese family and one sporadic case of with HL. The family members exhibited an autosomal dominant pattern of inheritance with the involvement of all the fingers and toenails in all the patients. Of interest, most of the affected members had koilonychia during their childhood. Thus, the present study first used gene mapping with an aim to identify the pathogenic gene underlying koilonychia. Through genomewide linkage analysis, the pathogenic area of koilonychia was identified on chromosome 3 with multipoint Log of Odds scores >2. A novel pathogenic mutation c.1384G>A (p.E462K) was identified in the PLCD1 gene in all the patients in the family, which confirmed the diagnosis of hereditary leukonychia. A novel mutation c.770G>A (p.R257H) was also detected in one sporadic case of leukonychia. On the basis of these findings and of previous studies, it is suggested that hereditary leukonychia may initially present as koilonychia, whereas hereditary koilonychia does not progress to leukonychia. Moreover, the present study identified two pathogenic variants of the PLCD1 associated with hereditary leukonychia, and highlights the significance of genetic diagnosis.
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Hipopigmentación/genética , Enfermedades de la Uña/congénito , Uñas Malformadas/genética , Fosfolipasa C delta/genética , Adulto , Niño , Femenino , Humanos , Hipopigmentación/patología , Masculino , Mutación Missense , Enfermedades de la Uña/genética , Enfermedades de la Uña/patología , Uñas Malformadas/patología , LinajeRESUMEN
Decreased or increased activity of potassium channels caused by loss-of-function and gain-of-function (GOF) variants in the corresponding genes, respectively, underlies a broad spectrum of human disorders affecting the central nervous system, heart, kidney, and other organs. While the association of epilepsy and intellectual disability (ID) with variants affecting function in genes encoding potassium channels is well known, GOF missense variants in K+ channel encoding genes in individuals with syndromic developmental disorders have only recently been recognized. These syndromic phenotypes include Zimmermann-Laband and Temple-Baraitser syndromes, caused by dominant variants in KCNH1, FHEIG syndrome due to dominant variants in KCNK4, and the clinical picture associated with dominant variants in KCNN3. Here we review the presentation of these individuals, including five newly reported with variants in KCNH1 and three additional individuals with KCNN3 variants, all variants likely affecting function. There is notable overlap in the phenotypic findings of these syndromes associated with dominant KCNN3, KCNH1, and KCNK4 variants, sharing developmental delay and/or ID, coarse facial features, gingival enlargement, distal digital hypoplasia, and hypertrichosis. We suggest to combine the phenotypes and define a new subgroup of potassium channelopathies caused by increased K+ conductance, referred to as syndromic neurodevelopmental K+ channelopathies due to dominant variants in KCNH1, KCNK4, or KCNN3.
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Anomalías Múltiples/genética , Canalopatías/genética , Anomalías Craneofaciales/genética , Canales de Potasio Éter-A-Go-Go/genética , Fibromatosis Gingival/genética , Mutación con Ganancia de Función , Hallux/anomalías , Deformidades Congénitas de la Mano/genética , Discapacidad Intelectual/genética , Uñas Malformadas/genética , Canales de Potasio/genética , Canales de Potasio de Pequeña Conductancia Activados por el Calcio/genética , Pulgar/anomalías , Anomalías Múltiples/patología , Adolescente , Adulto , Canalopatías/patología , Niño , Anomalías Craneofaciales/patología , Femenino , Fibromatosis Gingival/patología , Hallux/patología , Deformidades Congénitas de la Mano/patología , Humanos , Discapacidad Intelectual/patología , Masculino , Uñas Malformadas/patología , Fenotipo , Pulgar/patologíaRESUMEN
Early diagnosis of Kawasaki disease (KD) is critical to allow prompt initiation of treatment and avoid cardiac complications. All children with KD have fever accompanied by clinical signs, with four of the five classic criteria for complete KD being mucocutaneous, thus creating an important role for dermatologists. Moreover, dermatologists must be familiar with other dermatological findings that are not included in the American Heart Association classification criteria but can support the diagnosis, particularly in incomplete forms of the disease. We review the skin manifestations described for KD and perform an overview of pathophysiological advances and new treatments.
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Síndrome Mucocutáneo Linfonodular/patología , Síndrome Mucocutáneo Linfonodular/fisiopatología , Piel/patología , Vacuna BCG/efectos adversos , Niño , Diagnóstico Diferencial , Diagnóstico Precoz , Edema/etiología , Edema/patología , Eritema/etiología , Eritema/patología , Exantema/etiología , Exantema/patología , Pie/patología , Mano/patología , Humanos , Isquemia/etiología , Labio/patología , Síndrome Mucocutáneo Linfonodular/diagnóstico , Uñas Malformadas/patologíaRESUMEN
DOORS syndrome is characterized by deafness, onychodystrophy, osteodystrophy, intellectual disability, and seizures. In this study, we report two unrelated individuals with DOORS syndrome without deafness. Exome sequencing revealed a homozygous missense variant in PIGF (NM_173074.3:c.515C>G, p.Pro172Arg) in both. We demonstrate impaired glycosylphosphatidylinositol (GPI) biosynthesis through flow cytometry analysis. We thus describe the causal role of a novel disease gene, PIGF, in DOORS syndrome and highlight the overlap between this condition and GPI deficiency disorders. For each gene implicated in DOORS syndrome and/or inherited GPI deficiencies, there is considerable clinical variability so a high index of suspicion is warranted even though not all features are noted.
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Anomalías Craneofaciales/genética , Glicosilfosfatidilinositoles/deficiencia , Deformidades Congénitas de la Mano/genética , Pérdida Auditiva Sensorineural/genética , Discapacidad Intelectual/genética , Proteínas de la Membrana/genética , Mutación Missense , Uñas Malformadas/genética , Convulsiones/genética , Adolescente , Secuencia de Aminoácidos , Animales , Consanguinidad , Anomalías Craneofaciales/metabolismo , Anomalías Craneofaciales/patología , Femenino , Expresión Génica , Glicosilfosfatidilinositoles/genética , Glicosilfosfatidilinositoles/metabolismo , Células HEK293 , Deformidades Congénitas de la Mano/metabolismo , Deformidades Congénitas de la Mano/patología , Pérdida Auditiva Sensorineural/metabolismo , Pérdida Auditiva Sensorineural/patología , Homocigoto , Humanos , Lactante , Discapacidad Intelectual/metabolismo , Discapacidad Intelectual/patología , Masculino , Proteínas de la Membrana/deficiencia , Uñas Malformadas/metabolismo , Uñas Malformadas/patología , Convulsiones/metabolismo , Convulsiones/patología , Alineación de Secuencia , Secuenciación del ExomaRESUMEN
Fingernail deformity is common, yet current methods used to define cosmetic appearance following trauma are mainly descriptive. In order to quantify the cosmetic appearance of the fingernail, we developed the Oxford Fingernail Appearance Score using a three stage iterative process. The score has five cosmetic components marked as binary outcomes composed of nail shape, nail adherence, eponychial appearance, nail surface appearance and presence of a split. In the first stage, two assessors independently assessed 25 photographs of fingernails taken at a minimum of four months following paediatric nail bed repair and compared them to the corresponding contralateral uninjured finger. Following refinement in the score, ten different assessors scored a further 62 photographs of fingernails taken after paediatric nail bed repair. Assessors completed each of the five components, and the overall component score was calculated by statisticians post-hoc, taking the ideal appearance of each component as 1 ("identical to opposite" for nail shape, eponychium and surface, "complete" for adherence, "absent" for split) and all the non-ideal appearances as 0. Assessors effectively scored the photographs' integer values between 0 (least optimal appearance) and 5 (most optimal appearance). Refinements in the scoring system resulted in an improvement in a weighted kappa statistic of 0.36 (95% CI:0.09,0.68) in the initial score to 0.52 (95% CI: 0.42, 0.61). The Oxford Fingernail Appearance Score is a user-friendly and reliable scoring system which has application in a clinical trial setting.
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Traumatismos de los Dedos/complicaciones , Uñas Malformadas/clasificación , Uñas Malformadas/patología , Niño , Humanos , Uñas Malformadas/etiología , Variaciones Dependientes del Observador , FotograbarAsunto(s)
Biopsia/métodos , Uñas/patología , Humanos , Uñas/cirugía , Uñas Malformadas/patología , Uñas Malformadas/cirugíaRESUMEN
Twenty-Nail-Dystrophy (TND) also referred to as Trachyonychia is a disorder of the nails. It can affect all the nails hence the name. Trachyonychia is characterized by nail roughness, longitudinal ridging, fragility and hyper-pigmentation. It can occur in all ages and respond poorly to treatment. With this background, we report the case of a five year old girl with this disorder.
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Enfermedades de la Uña/diagnóstico , Uñas Malformadas/diagnóstico , Preescolar , Femenino , Hospitales Pediátricos , Humanos , Hiperpigmentación/diagnóstico , Hiperpigmentación/patología , Queratodermia Palmoplantar/diagnóstico , Queratodermia Palmoplantar/patología , Enfermedades de la Uña/patología , Uñas Malformadas/patología , Nigeria , Pacientes Ambulatorios , Centros de Atención TerciariaRESUMEN
The spectrum of peroxisomal disorders is wide and comprises individuals that die in the first year of life, as well as people with sensorineural hearing loss, retinal dystrophy and amelogenesis imperfecta. In this article, we describe three patients; two diagnosed with Heimler syndrome and a third one with a mild-intermediate phenotype. We arrived at these diagnoses by conducting complete ophthalmic (National Eye Institute), auditory (National Institute of Deafness and Other Communication Disorders), and dental (National Institute of Dental and Craniofacial Research) evaluations, as well as laboratory and genetic testing. Retinal degeneration with macular cystic changes, amelogenesis imperfecta, and sensorineural hearing loss were features shared by the three patients. Patients A and C had pathogenic variants in PEX1 and Patient B, in PEX6. Besides analyzing these cases, we review the literature regarding mild peroxisomal disorders, their pathophysiology, genetics, differential diagnosis, diagnostic methods, and management. We suggest that peroxisomal disorders are considered in every child with sensorineural hearing loss and retinal degeneration. These patients should have a dental evaluation to rule out amelogenesis imperfecta as well as audiologic examination and laboratory testing including peroxisomal biomarkers and genetic testing. Appropriate diagnosis can lead to better genetic counseling and management of the associated comorbidities.
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ATPasas Asociadas con Actividades Celulares Diversas/genética , Amelogénesis Imperfecta/genética , Pérdida Auditiva Sensorineural/genética , Proteínas de la Membrana/genética , Uñas Malformadas/genética , Trastorno Peroxisomal/genética , Adolescente , Adulto , Amelogénesis Imperfecta/complicaciones , Amelogénesis Imperfecta/diagnóstico , Amelogénesis Imperfecta/patología , Niño , Femenino , Asesoramiento Genético , Pérdida Auditiva Sensorineural/complicaciones , Pérdida Auditiva Sensorineural/diagnóstico , Pérdida Auditiva Sensorineural/patología , Humanos , Masculino , Uñas Malformadas/complicaciones , Uñas Malformadas/diagnóstico , Uñas Malformadas/patología , Linaje , Trastorno Peroxisomal/complicaciones , Trastorno Peroxisomal/diagnóstico , Trastorno Peroxisomal/patología , Fenotipo , Degeneración Retiniana/diagnóstico , Degeneración Retiniana/genética , Degeneración Retiniana/patología , Adulto JovenRESUMEN
BACKGROUND: Brachydactyly (BD) is a rare autosomal dominant inherited disease characterized by shortness of the fingers and/or toes, which has been classified into the subtypes A-E. However, the exact cause and mechanism of BD remain to be illuminated. Here, we aim to reveal the clinical and genetic characteristics of a subtype of BD, brachydactyly-anonychia. METHODS: In this study, a large Chinese family with three members affected by brachydactyly-anonychia was investigated. Both whole-exome sequencing and microarray-based comparative genomic hybridization (CGH) were performed on this family and the results of copy number variation (CNV) were verified by quantitative real-time PCR (qPCR). RESULTS: All the affected individuals showed short fingers and toes as well as missing nails; and the absence of middle phalanges in figure II-V of the upper and lower extremities was observed by X-ray examination. A duplication involving in the region of 17q24.3 was detected by CGH. The results of qPCR also represented this duplication in 17q24.3 in all the patients. CONCLUSION: In summary, our findings suggest that 17q24.3 duplication is the genetic cause of brachydactyly-anonychia in this family, which support the prior report that brachydactyly-anonychia is associated with 17q24.3 duplication, and further indicates the pathogenic correlation between BD and CNVs.
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Braquidactilia/genética , Duplicación Cromosómica , Cromosomas Humanos Par 17/genética , Uñas Malformadas/congénito , Adulto , Braquidactilia/patología , Femenino , Humanos , Masculino , Uñas Malformadas/genética , Uñas Malformadas/patología , Linaje , Canales de Potasio de Rectificación Interna/genética , Factor de Transcripción SOX9/genéticaRESUMEN
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.