Kleefstra Syndrome 2: A Case Report

Abstract

Introduction: Kleefstra Syndrome (KS) represents 1 in 200,000 cases of intellectual disability. The KMT2C gene is associated with KS type 2. It is characterized by intellectual delay, motor disability, and facial dysmorphism.

Objective: To describe a case of KS.

Methods: An 8-year-old male, born to non-consanguineous parents, with a family history of epilepsy and developmental delay in the fourth degree. He was born at 40 weeks via vaginal delivery, with a negative STORCH screening, recurrent urinary tract infections, and a threatened miscarriage. He had no complications at birth, with a birth weight of 3,220 grams and a length of 50 cm. Developmental milestones included sitting at 24 months, walking at 12 months, and no speech. On physical examination, his height was 132 cm (+0.66 SD), weight 26 kg (+0.03 SD), head circumference 50 cm, with a slender face, upturned nose, café-au-lait spot, aphasia, no lingual movements, hypotonia, gait abnormalities, and developmental delay. Brain MRI showed hypomyelination, supratentorial T2 and FLAIR hyperintensities, thinning of the corpus callosum, and a Dandy-Walker variant arachnoid cyst in the temporal region. An echocardiogram showed a physiological foramen ovale. Electromyography was normal, as were auditory evoked potentials, thyroid profile, and quantitative amino acids in urine. Urinary reducing sugars were negative.

Results and Discussion: The patient had a normal karyotype 46 XY[25], negative genomic hybridization, and clinical exome sequencing identified a variant in the KMT2C gene c.11968G>A (p.Asp3990As) heterozygous VUS. This case shares features of developmental and psychomotor delay, aphasia, and microcephaly. The variant is not reported in genetic databases.

Conclusions: It is essential to understand the phenotypic spectrum of KS to enable early detection and provide appropriate care.