Clinical heterogeneity of Kabuki syndrome in a cohort of Italian patients and review of the literature

Abstract

Kabuki syndrome (KS) is a well-recognized disorder characterized by postnatal growth deficiency, dysmorphic facial features, skeletal anomalies, and intellectual disability. The syndrome is caused by KMT2D gene mutations or less frequently KDM6A gene mutations or deletions. We report a systematic evaluation of KS patients from Campania region of Italy; data were also compared with literature ones. We collected data of 15 subjects (8 males and 7 females with age range 10–26 years; mean age 16.9 years) with confirmed diagnosis of KS, representing the entire cohort of patients from Campania Region. Each patient performed biochemical testing and instrumental investigation. Neuro-intellectual development, cranio-facial dysmorphisms, and multisystem involvement data were collected retrospectively. For each category, type of defects and frequency of the anomalies were analyzed. Our observation shows that KS patients from Campania region have some particular and previously underscored, neurological and immunological findings. We found high prevalence of EEG’s abnormalities (43%) and MRI brain abnormalities (60%). Microcephaly resulted more common in our series (33%), if compared with major cohorts described in literature. Biochemical features of immunodeficiency and autoimmune diseases including thyroid autoimmunity, polyserositis, and vitiligo were observed with high prevalence (54.5%). Low immunoglobulins levels were a frequent finding. Lymphocyte class investigation showed significantly reduced CD8 levels in one patient.Conclusions: These data confirm great heterogeneity of clinical manifestations in KS and suggest to introduce further clinical diagnostic criteria in order to perform a correct and precocious diagnosis. What is Known• Kabuki syndrome is characterized by growth deficiency, dysmorphic facial features, skeletal anomalies, and intellectual disability• Immune dysfunction is a common finding but autoimmune diseases are rarely seen• Neurological features are common What is New• Some particular facial features could help gestalt diagnosis (hypertelorism, broad nasal bridge, micrognathia, tooth agenesis, cutaneous haemangiomas and strabismus)• Higher prevalence of autoimmune disorders than previously reported• Particular neurological features are present in this cohort (EEG and MRI brain abnormalities)

Vitiligo in a Patient With Kabuki Syndrome: Case Study and Review of the Literature

“…Other characteristics seen in these patients include recurrent respiratory tract infections, otitis media, cardiac anomalies, hypogammaglobulinemia, developmental delay, gastrointestinal abnormalities, hypodontia, joint hyperlaxity, hearing loss, cleft palate, renal malformations, and other autoimmune conditions. Four patients had a concurrent autoimmune condition: Hashimoto thyroiditis, autoimmune thyroiditis, primary sclerosing cholangitis, and ITP (Table 2 ) [ 1 - 4 , 7 - 13 ].…”

Investigation of genetic and phenotypic heterogeneity in 37 Turkish patients with Kabuki and Kabuki‐like phenotype

“…It is known that female patients with KDM6A pathogenic variants have milder cognitive impairment compared to male patients with KDM6A or KMT2D pathogenic variants (Bögershausen et al, 2016). Moreover, long halluces and large central incisors were seen in the patients with KDM6A variant, dissimilar to typical KS features (Banka et al, 2015;Di Candia et al, 2022;Lederer et al, 2012;Miyake et al, 2013;Wang et al, 2019). The girl with KDM6A variant presented here had severe short stature (À2.51 SD) and ID (IQ: 31), autism, premature thelarche, hypothyroidism, and long halluces (Figure 2s).…”

Autoimmune cytopenia and Kabuki syndrome in paediatrics: Insights in 11 patients

“…Four KS patients had cITP, and seven patients had ES: cITP + AIHA (n = 2), cITP + AIN (n = 2) and cITP + AIHA + AIN (n = 3). The median age at the initial diagnosis of cytopenia was 7 years (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). The median followup after the initial AIC diagnosis was 17 years .…”

“…[1][2][3] Various other symptoms may be associated. [4][5][6][7] From 2018, international guidelines allow to classify the patients. 4 KS has an estimated prevalence of 1/32 000.…”