Stuve–Wiedemann syndrome: Is it underrecognized?

Abstract

Stuve-Wiedemann Syndrome (SWS) (OMIM #601559) is an autosomal recessive disorder characterized by skeletal changes, bowing of the lower limb, severe osteoporosis and joint contractures, episodic hyperthermia, frequent respiratory infections, feeding problems and high mortality in early life. It is caused by mutation in the leukemia inhibitory factor receptor gene (LIFR; 151443) on chromosome 5p13. We provide the clinical follow-up and molecular aspects of six new patients who carried the same novel mutation in the LIFR gene (p.Arg692X) and three patients carried a common haplotype at the LIFR locus supporting a founder effect in the Turkish population. The probable pathogenesis of the features is also discussed. Osseous findings in the presence of other above-mentioned morbid conditions should raise the suspicion of SWS in neonates especially in Arabic and Eastern Mediterranean countries with high rate of consanguineous marriages like in Turkey. Severe osteoporosis, bone deformities, milias, leukocoria, inflammatory lesions on distal extremities, tongue biting behavior and oral ulcers could be more prominent features of the survivors beyond the neonatal period while respiratory and feeding problems are remitting. It is of crucial importance to diagnose such babies earlier in order to prevent extensive laboratory workup and to provide proper genetic counseling.

Unusual Stüve‐Wiedemann syndrome with complete maternal chromosome 5 isodisomy

“…Abnormal sensation has not yet been documented in STWS and our patient had not voiced sensory complaints. A few clinical reports hinted at possible insensitivity to pain in CISS and STWS, as some children show little pain with recurring fractures 13,19. These observations require future study.…”

Effects of leukemia inhibitory receptor gene mutations on human hypothalamo–pituitary–adrenal function

“…We found an identical haplotype for three markers over a 1.5 Mb region of chromosome 5 that spanned the LIFR locus (LIFR-CA, FYB-CA and D5S418), suggesting a founder effect in our patients. The patients did not receive any treatments that can suppress HPA axis [16].…”

“…They were all diagnosed between 2009 and 2011 in Zeynep Kamil Maternity and Childrens Diseases Research and Training Hospital. Clinical features of the patients were depicted in detail elsewhere [16]. Biochemical studies and dynamic tests were performed with the approval of local institutional ethics committee and all families gave written consent for studies.…”

Stüve-Wiedemann Syndrome: Update on Clinical and Genetic Aspects

“…In addition, a recurrent frameshift variant (c.653dup) and a nonsense mutation (c.2074C>T) were identified in families from the United Arab Emirates and Turkey respectively, indicating a founder effect in these regions [Dagoneau et al, 2004;Yeşil et al, 2014].…”