Wiedemann–Steiner syndrome: Three further cases

Abstract

We describe three patients with a syndrome comprising arched, thick eyebrows, hypertelorism, narrow palpebral fissures, broad nasal bridge and tip, long philtrum, thin upper lip, stubby hands and feet, hirsutism, and severe psychomotor retardation. These patients expand the phenotype of the Wiedemann-Steiner syndrome and delineate it as an entity.

Delineation of clinical features in Wiedemann–Steiner syndrome caused by KMT2A mutations

“…S1 and Table S2). The same hand phenotype has been reported in one WSS patient although it is not known whether she has KMT2A abnormality. In addition, abnormal dermatoglyphics and prominent digit pads were frequently observed in our WSS patients but have not been previously reported.…”

De Novo variants in the KMT2A (MLL) gene causing atypical Wiedemann-Steiner syndrome in two unrelated individuals identified by clinical exome sequencing

“…Our patients shares several of the features of KMT2A -associated WSS, including postnatal growth retardation, developmental delay, wide nasal bridge, broad/bulbous nasal tip, and downslanted palpebral fissures [9,30]. They do not however have clear hypertrichosis cubiti, the clinical feature most readily associated - but not pathognomonic - with WSS.…”

Whole exome sequencing reveals a MLL de novo mutation associated with mild developmental delay and without ‘hairy elbows’: expanding the phenotype of Wiedemann–Steiner syndrome

“…Discussion WSS was first described in 1989 by Wiedemann et al (1989) with the case of a child with short stature, hypertelorism and other dysmorphic features and moderate developmental delay. A second case was identified by Steiner and Marques (2000), and several other cases of WSS have since been reported (Visser et al 2002;Koç et al 2007;Koenig et al 2010;Mendelsohn et al 2014). Jones et al (2012) identified heterozygous mutations of the MLL gene in five out of six children with clinical features of WSS.…”

“…Notably, also intragenic deletion and missense variations of the MLL gene have been recently reported as the molecular cause of phenotypes within the WSS-related clinical spectrum (Mendelsohn et al 2014;Strom et al 2014). Although Wiedemann's original description did not include hypertrichosis cubiti, this has been a consistent feature in most of the cases subsequently reported, including all the three discussed by Koenig et al (2010), and all five of those found to have mutations affecting MLL in Jones et al (2012). Notably, the sixth case of the study by Jones et al (2012) who had no MLL mutation was also the only one who did not display hairy elbows.…”

“…Wiedemann-Steiner syndrome (WSS; MIM: 605130) is a rare autosomal dominant condition characterized by developmental delay, short stature and dysmorphic features (Wiedemann et al 1989;Koenig et al 2010). Hypertrichosis cubiti (i.e., excessive hair on the elbows) has been regarded as one of the most prominent feature of WSS and this condition has sometimes been also called as 'hairy elbows syndrome' (Polizzi et al 2005).…”