Table 1 Clinical phenotype of the family
From: Cold-aggravated pain in humans caused by a hyperactive NaV1.9 channel mutant
Symptoms | I.1 | II.1 | II.3 | III.2 | III.4 |
|---|---|---|---|---|---|
Pain | |||||
LocationSkin changes | Lower extremities, occasionally upper. Starts in joints (ankles, knees, elbows, wrists only) and radiates to arms and legs Occasional hives | Lower extremities, less commonly upper extremities. Starts in joints and radiates into arms or legsUnknown | Lower extremities, occasionally upper. Starts in joints and radiates to arms and legs Occasional flushing of neck and chest when young | Lower extremities, less commonly upper extremities. Starts in joints and radiates into arms or legsUnknown | Lower extremities, occasionally upper. Starts in joints and radiates to arms and legs Occasional flushing of neck and face, and sweating |
Onset | Infancy. Pain episodes can occur any time | Unknown | Since age 18 months. Pain episodes can occur any time but more at night | Infancy | Since age 10 months. Pain episodes often occur late afternoon/early evening |
Triggers | Gluten | Cold temperature | Gluten ‘When there is stress on the body, such as exhaustion and illness’ | None reported | Cold temperature, gluten, nitrates ‘When there is stress on the body, such as exhaustion and illness’ |
Frequency | 2–3 times/month with lifestyle modifications and medication | 2–3 times/month | 2–3 times/month with lifestyle modifications and medication | 2–3 times/month | ∼60 times/month if no treatment. 2–3 times/month with lifestyle modifications and medication |
Duration | If no medication, cycling between 20 min of pain and 20 min without pain for 3 h | 20–30 min | 20–30 min | 20–30 min | 20–30 min |
Responsiveness to medication | Ibuprofen prophylactically | Ibuprofen | Ibuprofen | Ibuprofen Naproxen | Ibuprofen Naproxen Colchicine |
Consequence | Impairs desire to walk and fine motor manipulation Desire to keep arms and legs in certain positions and move them in certain ways to alleviate pain | Walking uncomfortable | Impairs desire to walk and fine motor manipulation Desire to keep arms and legs in certain positions and move them in certain ways to alleviate pain | Walking uncomfortable | Impairs desire to walk and fine motor manipulation Desire to keep arms and legs in certain positions and move them in certain ways to alleviate pain |
Skin | |||||
Skin injuries caused by inability to feel pain | N | N | N | N | N |
Prolonged healing | N | N | N | N | N |
Cold/heat tolerance | |||||
Problem tolerating heat/cold | N | Sensitive to cold; pain somewhat eased by warmth | N | N | Sensitive to cold. Cold can cause leg pain |
Excess/insufficient sweating | N | N | N | N | N |
Development | |||||
Failure to thrive | N | N | N | N | N |
Intellectual disability | N | N | N | N | N |
Motor delay | N | N | N | N | N |
Gastrointestinal | |||||
Constipation | Yes, since age 18 years | N | Yes, since age 18 years | N | N |
Diarrhoea | Yes, since age 18 years | N | Severe pain causes diarrhoea | N | Severe pain causes diarrhoea |
Pain passing stool | N | N | N | N | N |
Psychology | |||||
Psychological, emotional problems | N | N | N | N | N |
Musculoskeletal | |||||
Joint issues | N | N | N | N | N |
Muscle weakness | N | N | N | N | N |
