RESUMO
PIGT is one of over 29 glycosylphosphatidylinositol biosynthesis defect genes. Mutations cause genetically determined disorders characterized mainly by epilepsy with fever-sensitivity, central hypotonia, psychomotor delay and congenital malformations. The disease is known as multiple congenital anomalies-hypotonia-seizures syndrome 3 (MCAHS3) or glycosylphosphatidylinositol biosynthesis defect-7. Twenty-eight cases have been reported until today. We present seven novel Polish patients, all harboring 1582G>A variant in a homozygous or compound heterozygous state which seems to cause a milder phenotype of the disease.
Assuntos
Aciltransferases/genética , Epilepsia/genética , Glicosilfosfatidilinositóis/deficiência , Deficiência Intelectual/genética , Transtornos Psicomotores/genética , Convulsões/genética , Criança , Pré-Escolar , Deficiências do Desenvolvimento/complicações , Deficiências do Desenvolvimento/genética , Deficiências do Desenvolvimento/patologia , Epilepsia/complicações , Epilepsia/patologia , Feminino , Citometria de Fluxo , Glicosilfosfatidilinositóis/genética , Homozigoto , Humanos , Lactente , Deficiência Intelectual/complicações , Deficiência Intelectual/patologia , Masculino , Mutação/genética , Malformações do Sistema Nervoso/complicações , Malformações do Sistema Nervoso/genética , Malformações do Sistema Nervoso/patologia , Linhagem , Fenótipo , Polônia , Transtornos Psicomotores/patologia , Convulsões/complicações , Convulsões/patologiaRESUMO
Kabuki Syndrome (KS) encompasses a spectrum of clinical manifestations, primarily attributed to pathogenic variants in the KMT2D gene. This study aims to elucidate novel features in KS patients with missense variants, contrasting their presentation with both literature-reported cases of patients with missense pathogenic variants as well as other KS patients with truncating pathogenic variants. Employing a survey questionnaire and clinical evaluations, we examined ten KS patients with missense variants, focusing on their dysmorphism characteristics, behavior and psychomotor development. We identified unique features in missense variant patients, including foot hyperesthesia, musicality, and sensory integration disorders. Notably, despite similarities in developmental trajectories, distinct phenotypic traits emerged in missense variant cases, suggesting a potential genotype-phenotype correlation. These findings contribute to a deeper understanding of KS heterogeneity and underscore the importance of genotype-specific characterization for prognostic and therapeutic considerations. Further exploration of genotype-phenotype relationships promises to refine clinical management strategies and enhance patient outcomes in this complex syndrome.
Assuntos
Antígenos de Neoplasias/imunologia , Autoanticorpos/imunologia , Proteínas do Tecido Nervoso/imunologia , Síndrome de Opsoclonia-Mioclonia/diagnóstico , Doenças Autoimunes do Sistema Nervoso/diagnóstico , Doenças Autoimunes do Sistema Nervoso/imunologia , Pré-Escolar , Feminino , Humanos , Síndrome de Opsoclonia-Mioclonia/imunologiaRESUMO
Kabuki syndrome (KS) is a rare developmental disorder principally comprised of developmental delay, hypotonia and a clearly defined dysmorphism: elongation of the structures surrounding the eyes, a shortened and depressed nose, thinning of the upper lip and thickening of the lower lip, large and prominent ears, hypertrichosis and scoliosis. Other characteristics include poor physical growth, cardiac, gastrointestinal and renal anomalies as well as variable behavioral issues, including autistic features. De novo or inherited pathogenic/likely pathogenic variants in the KMT2D gene are the most common cause of KS and account for up to 75% of patients. Variants in KDM6A cause up to 5% of cases (X-linked dominant inheritance), while the etiology of about 20% of cases remains unknown. Current KS diagnostic criteria include hypotonia during infancy, developmental delay and/or intellectual disability, typical dysmorphism and confirmed pathogenic/likely pathogenic variant in KMT2D or KDM6A. Care for KS patients includes the control of physical and psychomotor development during childhood, rehabilitation and multi-specialist care. This paper reviews the current clinical knowledge, provides molecular and scientific links and sheds light on the treatment of Kabuki syndrome individuals.
Assuntos
Anormalidades Múltiplas/patologia , Proteínas de Ligação a DNA/genética , Face/anormalidades , Doenças Hematológicas/patologia , Histona Desmetilases/genética , Mutação , Proteínas de Neoplasias/genética , Fenótipo , Doenças Vestibulares/patologia , Anormalidades Múltiplas/genética , Face/patologia , Doenças Hematológicas/genética , Humanos , Doenças Vestibulares/genéticaRESUMO
The clinical picture of BRCA1-associated protein required for ATM activation-1 (BRAT1) comprises retractable early-onset epileptic encephalopathy, progressive microcephaly, and early demise. Both, inter- and intrafamilial variations of features of BRAT1-associated disease have been described. Here, the familial case of a brother and sister with homozygous pathogenic variants in BRAT1 is presented with special emphasis on differences in seizure type/onset and central nervous system lesions. The neuropathology is extensively discussed and hypotheses put forward that may shed light on etiology of brain symptomatology within the context of BRAT1 mutations.