Bone Abstracts

Background: Stuve–Wiedemann syndrome (SWS, OMIM 601559) is a severe autosomal recessive condition characterized by bowing of the lower limbs with cortical thickening, wide metaphyses, abnormal trabecular pattern and camptodactyly. Additional features include dysautonomia symptoms with temperature instability, respiratory distress and sucking/swallowing difficulties in the first months of life.

Most SWS cases do not survive beyond the first year of age, unexplained hyperthermia and respiratory distress being a frequent cause of death. The number of survivors is small, and it is not known at present what proportion of infants with SWS may survive.

Therefore, the clinical phenotype with age has not yet been clearly characterized.

Presenting problem: Here we report on the natural history of a girl with SWS, born from two consanguineous Romanian parents. She presented osteodysplastic signs and autonomic nervous system symptoms: lack of corneal reflex and neuropathic keratitis, absence of fungiform papillae, paradoxical sweating at low temperature, patellar hyporeflexia, and progressive scoliosis.

The diagnosis was molecularly confirmed in Paris by the detection of a homozygous mutation in exon 7 of LIFR gene: c.756_757insT.

At the age of 9 years old she developed significant joint swelling of both knee with subsequent inability to walk. Doppler-US detected synovial hypertrophy and significant effusion.

Clinical management: Coagulation, metabolic, endocrine, and immunological studies were all normal with the exception of elevated C-reactive protein (three, normal value <0.5 mg/dl) and serum alkaline phosphatase levels (1.439 U/l; normal values 145–420 U/l).

Radiographically, our patients have a pattern of bowing, metaphyseal undertubulation, rarefaction, and striation that has been reported before in long-term survivors.

In order to avoid the progressive decrease in knee mobility described in survival patients that lead to became wheelchair dependent, ultrasonography was used for guidance of synovial aspiration and steroid injection. Synovial fluid cell count showed a white cell count of about 1000 with prevalence of monocyte cells. The increased synovial fluid appears to originate from dilated capillaries adjacent to altered joint structures, suggesting a primary role for mechanical factors.

Discussion: Follow-up beyond adulthood will permit to better define the range of the clinical manifestations, and the natural history in adulthood.

References: 1. Stuve A & Wiedemann HR. Congenital bowing of the long bones in two sisters. Lancet 1971 2 495.

2. Gaspar IM, Saldanha T, Cabral P, Manuel Vilhena M, Tuna M, Costa C, Dagoneau N, Daire VC & Hennekam RCM. Long-term follow-up in Stuve–Wiedemann syndrome. Am J Med Genet Part A 2008 146A 1748–1753.

3. Stüve-Wiedemann syndrome: long-term follow-up and genetic heterogeneity. Clin Genet 77 266–272.