RESUMEN
Kabuki syndrome (OMIM #147920 and 300867) is a rare genetic disorder characterized by a distinctive facial gestalt, intellectual disability and multiple congenital anomalies. We summarized the clinical features and molecular findings of the Kabuki syndrome (KS) patients diagnosed in Hong Kong between January 1991 and December 2019. There were 21 molecularly confirmed KS. Twenty of them were due to pathogenic KMT2D variants and one patient had KDM6A deletion. Nine KMT2D variants were novel. The clinical phenotype of our Chinese KS patients was largely comparable with that reported in patients of other ethnicities. This study expands the mutation spectrum but also provide important natural history information of Chinese KS in literature.
Asunto(s)
Anomalías Múltiples/patología , Pueblo Asiatico/genética , Proteínas de Unión al ADN/genética , Cara/anomalías , Enfermedades Hematológicas/patología , Histona Demetilasas/genética , Mutación , Proteínas de Neoplasias/genética , Enfermedades Vestibulares/patología , Anomalías Múltiples/epidemiología , Anomalías Múltiples/genética , Adolescente , Adulto , Niño , Preescolar , Cara/patología , Femenino , Estudios de Seguimiento , Enfermedades Hematológicas/epidemiología , Enfermedades Hematológicas/genética , Hong Kong/epidemiología , Humanos , Lactante , Recién Nacido , Masculino , Fenotipo , Pronóstico , Enfermedades Vestibulares/epidemiología , Enfermedades Vestibulares/genética , Adulto JovenRESUMEN
Alström syndrome (AS) is a monogenic syndromic ciliopathy caused by mutations in the ALMS1 (Alström Syndrome 1) gene. A total of 21 subjects with AS from 20 unrelated Chinese families were recruited. Our cohort consists of 9 females and 12 males, between 5 months and 20 years old. The first symptom(s) appeared between 3 and 24 months. They were recorded to be either visual impairments (83%) or dilated cardiomyopathy (17%). Median time from symptom onset to seeking medical attention was 6 months (3-36 months) and the median time needed to reach the final molecular diagnosis is 54 months (6-240 months). System involvement at the time of the survey was as follows: visual symptoms (100%), hearing Impairment (67%), endocrine symptoms (43%), neurological symptoms (19%), hepatic symptoms (14%), and renal Involvement (14%). These findings are comparable to data reported in the literature. However, the proportion of subjects with cognitive impairment (33%) and behavioral problems (19%) were higher. Thirty-three unique mutations were identified in the ALMS1 gene, of which 18 are novel mutations classified as pathogenic/likely pathogenic according to the American College of Medical Genetics (ACMG) guideline. Four recurrent mutations were identified in the cohort, in particular; c.2084C>A, p. (Ser695Ter), is suggestive to be a founder mutation in people of Chinese ancestry. The participation of AS subjects of differing ethnicities is essential to improve the algorithm in facial recognition/phenotyping, as well as to understand the mutation spectrum beyond than just those of European ancestry.