Endocrine Abstracts

Introduction: Kabuki syndrome (KS) is a rare congenital, multisystemic disorder caused by pathogenic variants of KMT2D or KDM6A genes, causing autosomal dominant KS type 1 (more than 80%) and X-linked KS type 2 respectively. The phenotype spectrum is highly variable, consisting of a mixture of any of the five cardinal features (facial dysmorphic features, skeletal defects, dermatoglyphic abnormalities, various degrees of intellectual and growth retardation) with structural disorders comprising ophtalmologic, auricular, dental, cardiac, gastro-intestinal, genitourinary disorders and other conditions such as seizures, autoimmune or endocrine-related disorders (growth hormone deficiency (GHD), hyperinsulinemia, delayed sexual development, early thelarche or diabetes insipidus).

Case report: Our 4-year-old female patient was born prematurely via caesarian section at 32 gestational weeks, with a birth weight of 2300g. She had a history of infantile hypotonia, developmental delay, astigmatism, right renal hypoplasia and medullary nephrocalcinosis treated with Hydrochlorothiazide. At the first assessment in the Endocrinology clinic, she presented prominent, low-set ears, long palpebral fissures, flattened nose, enlarged thorax base, short stature at -3.04 SD according to Romanian synthetic growth charts, at -2.08 SD compared to the target height, healthy weight at 11^th percentile and a perfectly normal neuro-psychomotor development. The genetic test was positive for a heterozygous complete deletion of the coding regions of KDM6A gene, and the karyotype disclosed a Turner mosaicism 46,X,i(X)(q10)/45,X/46,XX[17]/[14][1]. IGF-1 level was in the normal range, the GH secretion was not stimulated consecutive to glucagon administration.

Discussions: The occurrence of both Kabuki and Turner syndrome has been cited in several case reports, and may express overlapping features, such as short stature, hyperinsulinism or congenital heart diseases. The clinical characteristics of X-linked KS type 2 have been less studied than the 1^st type. The females were observed to be less prone to severe phenotypes than male-affected individuals. Short stature is a common feature in patients with KS, not necessarily related to GHD; however, the genotype-phenotype correlations suggest a direct relationship with KMT2D mutations, while short stature is less frequent in the KDM6A group. Turner karyotype serves as an indication for rh-GH therapy, which may significantly improve the prognosis of our patient.