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 Orthopedics, Gallivare Hospital, Gallivare, Sweden.

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-delta fibres 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.