IMPE Abstracts

Wiedemann-Steiner Syndrome (WDSTS) is an autosomal dominant disorder with a broad and variable spectrum, characterized by intellectual disability (ID), prenatal and postnatal growth retardation, hypertrichosis, characteristic facial features, behavioral problems, and congenital anomalies involving different systems. A total of three patients were diagnosed with novel pathogenic mutations in the KMT2A gene in our hospital. Our first patient was a 15-month-old girl found by Trio-based whole exome sequencing (Trio-WES) to carry a novel de novo missense mutation of KMT2A (c.3566G>T). She had ID, growth delay, psychomotor retardation, hypertrichosis, characteristic facial features (thick and arched eyebrows, down-slanting palpebral fissures, thick hair, and a broad nasal tip), small and puffy hands, fat pads anterior to calcanei, and palmar/plantar grooves. Our second patient was a five-year-old boy who was diagnosed with WDSTS based on the results of Trio-WES and an assessment of his clinical features. He had ID, short stature, hirsutism, and facial features including a low hairline, down-slanting palpebral fissures, long eyelashes, thick and arching eyebrows, synophrys, a bulbous nose, and a broad nasal tip. The results of Trio-WES showed that the patient had a heterozygous nonsense mutation in the KMT2A gene c.7009C>T. However, not all individuals with WDSTS exhibit the classic phenotype. Our third patient was a 2-year-old girl with ID, facial dysmorphism, generalized hypertrichosis, and significant developmental delay. She just had long eyelashes, a bulbous nose, and mild down-slanting palpebral fissures without vertically narrow palpebral fissures, hypertelorism, thick eyebrows, and ptosis. The girl subsequently underwent genetic testing showed that compound heterozygous pathogenic variants (c.5803-2(IVS21)A>G) in KMT2A. Additionally, to enhance the awareness of clinicians and promote the diagnosis and treatment of the disease, we review previously reported WDSTS cases. We reviewed 249 patients with WDSTS and found that not all individuals with WDSTS exhibit the classic phenotype, and spectrum of the disorder can vary widely, from relatively atypical facial features to multiple systemic symptoms. Nevertheless, there remains the requirement for long-term follow-up assessments by an outpatient visit or by telephone because the phenotypic characteristics may develop in patients over time. What's more, there is still a lack of an international consensus, with increasing numbers of confirmed cases. Here, we summarize the clinical and molecular spectrum, diagnosis and differential diagnosis, long-term management, and care planning of WDSTS to improve the awareness of both pediatricians and clinical geneticists and to promote the diagnosis and treatment of the disease.