Tourette-like syndrome secondary to Kleefstra syndrome 1 with a de novo microdeletion in the EHMT1 gene.

BACKGROUND: Gills de la Tourette syndrome (TS) is a childhood-onset neurodevelopmental disorder manifested by motor and vocal tics. Kleefstra syndrome 1 (KS1), a rare genetic disorder, is caused by haploinsufficiency of the EHMT1 gene and is characterized by intellectual disability (ID), childhood hypotonia, and distinctive facial features. Tourette-like syndrome in KS1 has rarely been reported. CASE PRESENTATION: Here we describe a 7-year-old girl presenting involuntary motor and vocal tics, intellectual disability, childhood hypotonia, and dysmorphic craniofacial appearances, as well as comorbidities including attention deficit-hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and self-injurious behavior (SIB). The patient's CNV-seq testing revealed a de novo 320-kb deletion in the 9q34.3 region encompassing the EHMT1 gene. CONCLUSIONS: This is the first case reporting Tourette-like syndrome secondary to KS1 with a de novo microdeletion in the EHMT1 gene. Our case suggests TS with ID and facial anomalies indicate a genetic cause and broadens the phenotypic and genotypic spectrum of both TS and KS1.

A Korean male with Kleefstra syndrome presented with micropenis.

Kleefstra syndrome is caused by chromosome 9q34.3 deletion or heterozygous mutations in the euchromatin histone methyl transferase 1 (EHMT1) gene. It can be accompanied by intellectual disability, distinctive facial features, microcephaly, psychiatric disorders, hypotonia in childhood, hearing loss, heart defects, renal defects, epilepsy, speech anomalies, and obesity. Furthermore, genital anomalies are present in 30%-40% of male patients with Kleefstra syndrome, but their mechanisms have not been elucidated. Herein, we report a patient with Kleefstra syndrome presenting with micropenis. The patient was transferred to Kyungpook National University Children's Hospital for management of imperforate anus on the day of birth. Physical examination revealed micropenis with stretched penile length of 0.9 cm and facial dysmorphisms, including hypertelorism and anteverted nares. Chromosomal microarray revealed 424-kb heterozygous deletion at chromosome 9q34.3 (arr[hg19] 9q34.3 (140,234,315-140,659,055)x1). Among the involved main OMIM genes, phenotypically relevant genes were EHMT1 and NSMF. Endocrinological investigation showed low basal gonadotropin and testosterone levels. Anterior pituitary hormones and steroid hormone levels were in the normal range. Testicular function was normal based on human chorionic gonadotropin stimulation test. The patient experienced improvement in penile length growth with intramuscular testosterone enanthate injection initiated at 4 months of age. The purpose of this study is to describe the etiology, endocrine laboratory tests, and treatment of micropenis in Kleefstra syndrome.

A case of neonatal Kleefstra syndrome with SLC2A1 gene mutation / 中华实用儿科临床杂志

The clinical data of a newborn with Kleefstra syndrome combined with SLC2A1 gene mutation in the Department of Newborn Infants, Children′s Hospital of Nanjing Medical University were retrospectively analyzed.The laboratory examination, genetic characteristics, diagnosis and treatment progress were analyzed.This is the first report of a newborn with Kleefstra syndrome combined with SLC2A1 gene mutation, presenting with an early-onset epilepsy.Gene analysis is the most reliable method to make a definitive diagnosis.