ESPE Abstracts

Introduction: Kabuki Syndrome (KS) is a rare genetic disorder characterised by dysmorphic facies, poor developmental growth, hypotonia, skeletal abnormalities, intellectual disability, as well as systemic malformations. The pathogenic or likely pathogenic variants of the KMT2D or KDM6A genes are responsible for about 70% of the cases, while the rest are diagnosed based on clinical features consistent with KS. This paper reviews the clinical features, genetic testing and management of KS in a Romanian Pediatric Endocrinology clinic.

Methods: retrospective observational study.

Results: We examined data from 6 patients evaluated for KS in the Pediatric Endocrinology clinic, analyzing dysmorphia, growth development, malformations, intellectual abilities and genetic diagnosis. All were females, with ages between 2-18 years (average 9.9 years), with 5/6 having mild to severe intellectual disabilities. 3/6 already had a confirmed de novo KMT2D mutation, we tested the other 3 - 2 of them had Turner mosaicism with KS (2/6), while the other one didn’t present any known pathogenic mutation (1/6). 1/6 patients had a family history of Hashimoto’s thyroiditis and multiple sclerosis, with 3/6 cases having personal history of autoimmune thyroiditis and 1/6 suffering from psoriasis, atopic dermatitis and autoimmune thrombocytopenia. All (6/6) had elongated palpebral fissures, 3/6 had arched eyebrows with thinning of the external third, 3/6 had microcephaly, 2/6 had hypertelorism, with 6/6 having ear abnormalities. Scoliosis was present in 2/6 cases, brachydactyly in 2/6 patients, fetal pads were present in 1/6 patients and vertebral anomalies in 1/6 of cases. No cases presented hypotonia or hearing loss. Harmonious short stature was found in 4/6 of cases, with a mean of -2.5 SD, with all of the 4 patients either receiving treatment presently or having been treated in the past with rhGH. Multiple cardiac malformations were found in 2/6 patients and 2/6 presented with renal malformations, while 1/6 patients presented with arterial hypertension of unknown etiology.

Discussion: Genetic testing was positive for a de novo mutation in half of the patients, a smaller number of cases had Turner mosaicism with KS, with a minority having no pathogenic mutation. Some form of facial dysmorphia was present in all the cases, short stature was present in almost all the cases, skeletal abnormalities were present in a small number of cases, while malformations were found in a smaller number of patients.

Conclusions: KS is a rare genetic disorder with an identifiable mutation in most cases, which requires active surveillance for systemic complications.