Orthopedic aspects of familial insensitivity to pain due to a novel nerve growth

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Acta Orthop. 2006 Apr;77(2):198-202.

Orthopedic aspects of familial insensitivity to pain due to a novel

nerve growth factor beta mutation.

Minde J, Svensson O, Holmberg M, Solders G, Toolanen G.

Department of Surgery and Perioperative Science, Division of

Orthopedics, Umea University Hospital. Umea, SE-901 85.

Background

Congenital insensitivity to pain is a rare hereditary sensory

neuropathy Patients We present 6 patients from a family with a

mutation in the nerve growth factor beta gene (NGFB) Results 3

patients were homozygous with a mutilating arthropathy starting early

in life, and 3 patients were presumably heterozygous with a milder

course starting in adulthood. All patients had normal mental

abilities. In addition to absence of deep pain, the patients had

impaired temperature sensation, but no autonomic deficiency. Sural

nerve biopsies showed a moderate loss of A-deltafibres and a severe

reduction in C fibers.

Clinically, the disorder most often affected the lower extremities,

with an insidious progressive joint swelling or a painless fracture,

but the spine could also be involved with gross and unstable

spondylolisthesis. Fracture healing was uneventful, but the

arthropathy was progressive, eventually resulting in gross deformity

and instability. When treating patients with congenital disorders

such as this one, it is important to consider the slowly progressive

nature of the disorder, and the orthopedic operations should

therefore be planned from a long-term standpoint.

Arthrodesis, limb lengthening and spinal decompression or fusion are

the only elective procedures that seem reasonable. Fitting of

orthosis for joint protection is also demanding. To delay the

development of neuropathic arthropathy, patient education is

essential but difficult in the very young.

Interpretation

The different expression between homo- and heterozygous subjects and

the central role of nerve growth factor make this disease an

interesting model system for studies of disease mechanisms and the

molecular background to pain.