The progression of Wiedemann–Steiner syndrome in adulthood and two novel variants in the KMT2A gene

Abstract

Wiedemann–Steiner syndrome is a genetic condition associated with dysmorphic facies, hypertrichosis, short stature, developmental delay, and intellectual disability. Congenital malformations of the cerebral, cardiac, renal, and optic structures have also been reported. Because the majority of reported individuals with this condition have been under age 20, the long‐term prognosis is not well defined. Here we report on two further unrelated individuals diagnosed with Wiedemann–Steiner syndrome, one of whom is in her third decade of life. In addition, both individuals have novel KMT2A mutations. The information provided below about the outcome in Wiedemann–Steiner syndrome is important for families of affected individuals.

Expanding the phenotypic and genotypic spectrum of Wiedemann–Steiner syndrome: First patient from India

“…A striking feature in our patient was the absence of hypertrichosis cubiti which is considered an important feature of this syndrome (Figure c). Absence of this feature has been reported previously (Feldman, Dlouhy, Lah, & Payne, ). Therefore, its presence is specific, but its absence does not rule out the diagnosis.…”

Expanding the phenotype of Wiedemann‐Steiner syndrome: Craniovertebral junction anomalies

“…Lebrun et al (2018) described a 10‐year‐old female with radiological evidence of Chiari malformation type I, basilar impression, cervical C2/C3 vertebral fusion and C1/occiput fusion. In a further 2‐years‐old male patient, head and cervical CT scans and MRI revealed narrowing at the CVJ with mild posterior indentation at the upper cervical cord and possible C1 compression (Feldman et al, 2019).…”

“…We have recently resolved the diagnosis of a patient who, in addition to typical WDSTS features, presented with cervical C2/C3 vertebral fusion and small foramen magnum. At the same time, anomalies of the craniovertebral junction (CVJ) have been reported in a few other WDSTS patients (Baer et al, 2018;Feldman, Dlouhy, Lah, Payne, & Weaver, 2019;Lebrun et al, 2018), suggesting that they may warrant inclusion among the WDSTS-associated features.…”

Wiedemann-Steiner Syndrome as a Differential Diagnosis of Cornelia de Lange Syndrome Using Targeted Next-Generation Sequencing: A Case Report

“…Hypertrichosis cubiti has been observed in just about 60% of patients in large case series whereas intellectual disability, long eyelashes, hypertrichosis of the back, wide nasal bridge, thick eyebrows, thin upper lip vermilion, and hypertelorism were the most frequent findings in the patients [Aggarwal et al, 2017;Baer et al, 2018;Li et al, 2018]. The phenotypic changes among patient populations with WDSTS may partly be attributable to different ages of the patients in the literature [Feldman et al, 2019;Ramirez-Montaño and Pachajoa, 2019]. Hypertrichosis in the present case was mainly detected in lumbar and coccygeal regions, but she did not have hypertrichosis cubiti.…”