Femur fracture in a paediatric patient with hereditary hyaline fibromatosis syndrome

Background

Hereditary hyaline fibromatosis syndrome (HHFS) is an extremely rare autosomal recessive disease. It is characterised by the deposition of amorphous hyaline material in the viscera, skin and skeletal systems.1–3 The exact prevalence is unknown. The mainstay of treatment is currently symptomatic only.1–5

Mutations in the ANTXR2 gene are involved. ANTXR2 is involved in making proteins, which interact with components of the extracellular matrix. This pathway is ultimately involved in strengthening connective tissues. It is unclear why individuals present with varying severities of HHFS. Indeed, a diagnosis in infancy carries a poorer prognosis, and, in some cases, can be fatal. Mortality in childhood is often preceded by recurrent chest infections.1 2

Symptomatically, hyaline deposits can cause pain as well as complications from organ dysfunction. In more severely affected individuals, deposits in the intestines can lead to severe diarrhoea and cause failure to thrive. This further compromises the patient’s immune system. Specific to the skeletal system, joint stiffness and pain are often reported.1–5 Deformities and contractures are also recorded.5 Osteopenia and osteoporosis are a feature, and osteolysis can also occur at some joint surfaces, most notably at the hips.2–5

Case presentation

An 18-month-old girl with HHFS sustained a right oblique femur fracture after falling out of her mother’s arms when she was being bathed. The height of the fall was estimated to be less than half a metre. Her mother noticed that the child was crying when her right leg was lifted and presented without delay. The family had not noticed any visible deformity to the leg.

The patient had been diagnosed with HHFS on genetic analysis carried out at 2 months of age. She was homozygote for ANTXR2 c.1073dup. At the time of genetic screening, familial counselling was undertaken by paediatric and genetic specialists. At the time of injury, she was not on any medication to improve her bone density.

Her prognosis was described as palliative within 6 months of life due to her presenting clinical features. She had the following HHFS features: skin deposits and deposits in her intestines, which were under investigation when she presented. She suffered from proximal myopathy. This had resulted in an inability to sit up, crawl or walk. She had fixed flexion contractures of both hips and knees, and had been diagnosed with arthrogryposis at birth. She was being fed by a nasogastric tube due to failure to thrive. Additionally, she had already suffered from numerous previous admissions for staphylococcal infections.

The patient was otherwise well on presentation and no other injuries were identified. Non-accidental injury was screened for and ruled out. Her fixed flexion contractures meant that she held her legs in a frog leg position. Due to the severe proximal muscle weakness, she was only able to lie on her back in a bespoke pushchair and had limited or no movements in any of her limbs. She had no other obvious deformities but did have a small bruise on her right mid-thigh. She cried on palpation of her right thigh.

Investigations

An initial radiograph of the right femur was obtained (figure 1). It was difficult to get a full view due to the patient’s contractures, but later views are shown in figures 2 and 3. Radiolucent deposits are present in close proximity to the oblique femur fracture. Additionally, a chest radiograph (figure 4) demonstrates lucent lesions throughout the immature skeleton. Figures 5 and 6 were taken on day 1 in the hip spica. Figures 7 and 8 demonstrate the progress of the fracture healing. Figure 9 illustrates a skeletal survey image performed 18 months prior to the injury. No deposits in the femur are present at this point.

A bone profile on admission demonstrated the following: 25-hydroxycholecalciferol of 43 nmol/L, parathyroid hormone of 8.7 pmol/L, adjusted calcium of 2.53 mmol/L and phosphate of 1.39 mmol/L.

Differential diagnosis

Radiographs demonstrate that the patient had an oblique fracture of the right femur with surrounding features typical of HHFS. It is unclear whether the integrity of the bone was weakened by the presence of HHFS.

Treatment

The patient was treated with a multidisciplinary approach and was under the care of both the paediatric team and orthopaedic team.

An assessment of bone health was made, and she was commenced on cholecalciferol by the paediatricians, with a plan to follow her up and assess whether bisphosphonate treatment would be required.

With regard to the management of the femur fracture, due to the patient having fixed flexion deformities and proximal muscle weakness, in addition to the fracture being in relatively good alignment on presentation, a decision was made not to treat the fracture in conventional traction. The patient was placed in a spica cast within 24 hours of presentation. The fracture was maintained in good alignment in the spica (figures 5 and 6). As such, the patient was treated for 4 weeks in total in a hip spica, and followed up in the orthopaedic clinic and plaster room. Adequate callus was evident on a radiograph taken in clinic at the 4-week follow-up appointment and the spica was removed (figure 8).

Outcome and follow-up

The patient was referred to physiotherapy on discharge. She did not present with any further fractures in a 6-month period. The paediatric team continue to follow her up.