One in Three : Congenital Bent Bone Disease and Intermittent Hyperthermia in Three Siblings with Stuve-Wiedemann Syndrome

Abstract

Stuve-Wiedemann syndrome (STWS) is a rare disorder characterised by congenital bowing of the long bones, contractures of the joints, neonatal onset of respiratory distress, sucking and swallowing difficulties, dysautonomia presenting as episodic hyperthermia, and usually an early death. Three siblings from a consanguineous marriage presented with similar clinical features over 16 years. STWS was established with their last child at the beginning of 2012. All the children exhibited the onset of STWS in the neonatal period with fever and generalised hypotonia. Examinations of all the infants revealed camptodactyly, micrognathia, bent long bones with wide metaphyses, and hypotonia. Only the second affected child had myotonia, demonstrated by electromyography. Unusual pyrexia as a presenting feature in this syndrome needs early recognition so that extensive and elaborate investigations can be avoided. The disorder is usually caused by a mutation in the leukaemia inhibitory factor receptor gene.

The bHLH Protein Nulp1 is Essential for Femur Development Via Acting as a Cofactor in Wnt Signaling in Drosophila

“…To check how expression of dNulp1 was affected by the deletions in the on-target locus, we extracted total protein from dNulp1 1# and dNulp1 2# homozygous larvae. Western analysis using a fly nulp1 polyclonal antibody [ 16 ] showed that the full length dNulp1 protein was not expressed in dNulp1 1# and dNulp 1 2# homozygotes (Fig. 3C ).…”

“…Our results show that dNulp1 is essential for femur development and survival in Drosophila , which is similar to the major manifestation of congenital bent-bone dysplasia in human Stuve-Weidemann syndrome. A major phenotype in STWS patients is the bowing of the long bones (particularly the tibia and the femur) with frequent death in infancy [ 16 ]. While defects in the LIFR gene is one of the clinical molecular diagnostic markers, not all STWS patients have LIFR mutations, suggesting that other causative genes for STWS remain to be identified [ 27 ].…”

“…Stuve-Weidemann syndrome (STWS) is a rare congenital disorder in human with the major manifestation being bowing of the long bones (particularly the tibia and the femur) (OMIM #601559) and with frequent deaths in infancy [ 16 ]. The leukemia inhibitory factor receptor (LIFR) gene is considered to be the causative gene of the disease [ 16 ]. Loss of the LIFR gene in mice results in a phenotype similar to that of human STWS [ 17 ].…”

“…However, the mutations in the LIFR gene are found in only some patients with STWS. Other causative genes for STWS remain to be identified [ 16 ].…”

Stüve-Wiedemann syndrome: LIFR and associated cytokines in clinical course and etiology

“…However, STWS appears to be more common in the United Arab Emirates [14], as well as in Oman and Yemen [12,15]. …”