Wiedemann-Steiner syndrome caused by novel mutation of KMT2A gene: one case report and literature review

Abstract

Objective To analyze the clinical and biochemical, as well as genetic characteristics of a patient with Wiedemann-Steiner syndrome (WDSTS). Methods The clinical data of a patient with WDSTS were collected. The patient was treated with recombinant human growth hormone (rhGH) combined with gonadotrophine-releasing hormone agonist (GnRHa). Blood samples of the patient and her parents were taken for whole-Exome Sequencing (WES). Relevant literatures about KMT2A mutations were reviewed. Results The 5-year old girl presented with growth retardation, with height 100 cm (-2.4 SD), torpid reaction, and facial anomalies including low hairline, thick eyebrow and hair, hypertelorism, a wide nasal bridge. She had small and puffy hands and feet, excessive hair around back of neck, bilateral forearm and lower limbs. Her GH peak level was 26.6 ng/ml during GH stimulation test. She was re-examined at the age of 10.4 years, with severe short stature (120 cm/-3.58 SD) and a Tanner stage 2 of breast development. Her bone age was found to be approximately 11.4 years. Height increased from 120 cm at the age of 10.4 years to 147.3 cm after rhGH treatment combined with GnRHa for 2.5 years. rhGH therapy alone continued for 1.1 years and a height of 150 cm was reached at the age of 14.9 years, with bone age 14 years. Gene sequencing revealed a de novo frameshift mutation (c.10051delA, p. Thr3351Leufs*17) of exon 27 in KMT2A gene of the patient, but without any mutation in her parents. Through a literature review, seventy-one patients with WDSTS (including present case) presented with intellectual disability(70/71), facial anomalies (70/71), short stature (50/71), and hypertrichosis(39/71). Conclusion Patients presented with short stature, typical facial dysmorphism, intellectual disability, and hypertrichosis should be considered for WDSTS. The mutation p. Thr3351Leufs*17 in the KMT2A gene detected in our patient is a novel mutation. This is so far the first report of WDSTS patient who was successfully treated with a combination of GH and GnRHa at the onset of puberty to improve her adult height. Key words: Wiedemann-Steiner syndrome; KMT2A gene; Short stature; Hypertrichosis; Therapy