Abstract
KBG syndrome (KBGS) is a rare autosomal dominant inherited disease that involves multiple systems and is associated with variations in the ankyrin repeat domain 11 (ANKRD11) gene. We report the clinical and genetic data for 13 Chinese KBGS patients diagnosed by genetic testing and retrospectively analyse the genotypes and phenotypes of previously reported KBGS patients. The 13 patients in this study had heterozygous variations in the ANKRD11 gene, including seven frameshift variations, three nonsense variations, and three missense variations. They carried 11 variation sites, of which eight were previously unreported. The clinical phenotype analysis of these 13 patients and 240 previously reported patients showed that the occurrence rates of craniofacial anomalies, dental anomalies, global developmental delays, intellectual disability/learning difficulties, limb anomalies, and behavioural anomalies were >70%. The occurrence rates of short stature, delayed bone age, and spinal vertebral body anomalies were >50%. The frequency of global developmental delays and intellectual disability/learning difficulties in patients with truncated ANKRD11 gene variation was higher than that in patients with missense variation in the ANKRD11 gene (p < 0.05). Collectively, this study reported the genotypic and phenotypic characteristics of the largest sample of KBGS patients from China and discovered eight new ANKRD11 gene variations, which enriched the variation spectrum of the ANKRD11 gene. Variation in the ANKRD11 gene mainly caused craniofacial anomalies, growth and developmental anomalies, skeletal system anomalies, and nervous system anomalies. Truncated variation in the ANKRD11 gene is more likely to lead to global growth retardation and intellectual disability/learning difficulties than missense variation in ANKRD11.
Highlights
We describe 13 cases from China of KBG syndrome (KBGS) caused by variations in the ankyrin repeat domain 11 (ANKRD11) gene, update the phenotype and variation spectrum of KBGS, review and analyse the previously reported literature, summarize the clinical characteristics and genetic diagnosis of KBGS, and analyse the relationship between genotype and phenotype to guide clinical diagnosis and genetic counselling
ANKRD11 gene variation have been reported, some studies have shown cases of KBGS caused by ANKRD11 gene variation have been reported, some studies have that ANKRD11 variation accounts for approximately 1% of patients with unclear aetiology shown that ANKRD11 variation accounts for approximately 1% of patients with unclear of growth retardation [56]
The number of patients with KBGS reported at prebe far lower than those carrying ANKRD11 gene variation, which may be due to sent may be far lower than those carrying ANKRD11 gene variation, which may the incomplete understanding of the disease by many doctors, the variability in disease be due to the incomplete understanding of the disease by many doctors, the variability in phenotypes, and the mild phenotypes of some patients
Summary
KBG syndrome (KBGS, OMIM#148050) is a multisystem disorder, and “KBG” is derived from the initials of the surnames of three families who were first diagnosed with the disease in 1975 [1]. More than 300 cases have been reported. The typical manifestations are obvious craniofacial anomalies, macrodontia of the upper central incisors, skeletal anomalies, short stature, and growth and mental retardation. Hearing loss, congenital heart disease (CHD), cryptorchidism, and behavioural anomalies are common (similar to Cornelia de Lange syndrome, CdLS). The syndrome showed complete dominance, with varying degrees of expressivity between and within families.
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