Intragenic Deletion in the <b><i>LIFR</i></b> Gene in a Long-Term Survivor with Stüve-Wiedemann Syndrome

Abstract

Stüve-Wiedemann syndrome (SWS, OMIM 601559) is a rare autosomal recessive bent-bone dysplasia, caused by loss-of-function mutations in the leukemia inhibitory factor receptor (LIFR) gene, which usually leads to early death. Only few patients with long-term survival have been described in the literature. We report on a 5-year-old boy from a consanguineous marriage with molecular analysis for the LIFR gene. Sanger and next-generation sequencing (NGS) of LIFR were performed. Copy number variation analysis with NGS showed a novel mutation as the cause for the syndrome: an intragenic homozygous deletion in LIFR, involving exons 15-20. Bridging PCR was carried out to confirm the intragenic deletion. This is the first description of a large deletion in LIFR, broadening the spectrum of mutations in SWS. Besides the reported allelic heterogeneity, further studies such as exome sequencing are required to identify a novel gene in order to confirm the locus heterogeneity in SWS.

Clinical overview and outcome of the Stuve-Wiedemann syndrome: a systematic review

“…The third major concern since birth and during infancy are swallowing trouble (74%) which are probably consecutive to pharyngoesophageal dyskinesia due to an abnormal autonomic control [ 23 ]. Nasogastric tube feeding and/or gastrostomy are generally required during infancy to ensure proper feeding and prevent aspiration pneumonia [ 15 , 16 , 23 ]…”

Stüve‐Wiedemann syndrome with multiple eruptive vellus hair cysts and clefted tongue

“…Stüve‐Wiedemann syndrome is a rare syndrome with few cases reported and an estimated prevalence of less than 1/100 000. SWS is due to missense or nonsense mutations in the LIFR gene (5p13.1) . Characteristic clinical findings include camptodactyly, mask‐like facies, pursed mouth, and smooth tongue .…”

“…SWS is due to missense or nonsense mutations in the LIFR gene (5p13.1). 2,3 Characteristic clinical findings include camptodactyly, mask-like facies, pursed mouth, and smooth tongue. 3 In our case, transverse clefting of an otherwise fissured smooth tongue may have originated from repetitive self-biting due to loss of impulse control from autonomic nervous system dysfunction.…”

Stüve-Wiedemann Syndrome: Update on Clinical and Genetic Aspects

“…In the United Arab Emirates population, which is highly inbred and where termination of pregnancy is not accepted, the prevalence was estimated in 0.52/10,000 births [Al-Gazali et al, 2003a]. SWS has been described in different ethnic groups, including individuals from European countries [Wiedemann and Stüve, 1996;Cormier-Daire et al, 1998b;Dagoneau et al, 2004], Africa [Cormier-Daire et al, 1998b], North [Chen et al, 2001] and South America [Hatagami Marques et al, 2015], and the Middle East [Al-Gazali et al, 2003a;Dagoneau et al, 2004].…”