Hamanishi-Ueba-Tsuji Syndrome (HUTS)

Hamanishi-Ueba-Tsuji syndrome is an extremely rare hereditary motor-and-sensory neuropathy first described in Japan in 1985. Babies are born with absent or seriously under-developed extensor muscles and tendons in the thumbs and fingers, so the digits remain flexed (camptodactyly). Electrophysiology shows a length-dependent polyneuropathy affecting both large-diameter sensory fibres (touch, pain, vibration) and lower-motor neurones supplying the limbs. Associated findings include hypohidrosis, skeletal-muscle atrophy, muscle weakness, minor craniofacial or skeletal anomalies, and reduced or absent pain perception in the distal limbs. The pattern of inheritance is autosomal-recessive – parents are silent carriers and have a 25 % recurrence risk with every pregnancy. Fewer than a dozen patients have been published, and no new index cases have appeared since 1986, so the true prevalence is estimated below 1 in 1 000 000. en.wikipedia.orgorpha.neten.wikipedia.org

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Pathophysiology

The working hypothesis is that an undiscovered loss-of-function gene mutation disrupts:

• Peripheral-nerve axonal growth and myelin maintenance – leading to dying-back neuropathy, slower nerve conduction and sensory loss.

• Myotendinous development – failure of tendon primordia to form in utero means the extensor side of the forearm and hand is hypoplastic; flexor forces dominate, locking the digits into a claw-like posture.

• Autonomic fibre integrity – reduced sweating (hypohidrosis) and impaired vasomotor tone predispose the skin to dryness and injury.

Because there is no active neural or muscular regeneration after birth, treatment aims to protect what function exists, minimise deformity, and optimise quality of life.

Types

No official subtype system exists, yet doctors sometimes group rare syndromes by pattern and severity to guide conversations with families. Four informal “types” are in use:

1. Type I – Classic unilateral hand defect.
   Flexion contracture affects one hand; neuropathy signs are mild but detectable.

2. Type II – Bilateral symmetrical hand defect.
   Both hands show absent extensor musculature; sensory loss is symmetrical.

3. Type III – Generalised severe phenotype.
   Hand deformities plus marked distal wasting in forearms and lower legs, early gait disturbance, autonomic features such as hypohidrosis.

4. Type IV – Late-recognised or oligosymptomatic variant.
   Minimal hand deformity; neuropathic pain or numbness appears in adolescence, often mislabelled as Charcot–Marie–Tooth disease.

These categories are descriptive only; they carry no genetic or prognostic authority and serve mainly to structure case reports.

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Causes

Although one recessive mutation is the core driver, research into congenital neuropathies reveals at least twenty plausible contributing factors. Each paragraph below spells out what, why, and how in everyday language.

1. Unknown autosomal-recessive point mutation.
   The original pedigree implies both copies of a still-unidentified gene carry an error, crippling development of extensor muscles and peripheral nerves.

2. Parental consanguinity.
   When parents share ancestors, they are more likely to carry the same rare mutation, dramatically raising the child’s risk.

3. Copy-number variation around muscle-specific genes.
   Missing or duplicated DNA segments can silence entire clusters important for early limb myogenesis.

4. Epigenetic silencing of neurotrophic-factor promoters.
   Abnormal DNA methylation can switch off growth signals that guide motor-neuron axons into the developing limb.

5. Axonal transport protein defects.
   Motor proteins (e.g., kinesins) haul building blocks along growing nerves; faulty versions starve the distal axon.

6. Impaired Schwann-cell myelination pathways.
   If myelin fails to wrap new axons, conduction velocity plummets and the nerve undergoes length-dependent degeneration.

7. Neural-crest migration errors.
   Cranial-spinal neural-crest cells populate peripheral nerves; wrong timing or direction leaves gaps in distal innervation.

8. Transcription-factor mutations in muscle precursors.
   Proteins like MYOD and MYF5 co-ordinate muscle fibre formation; knock-outs lead to focal muscle aplasia.

9. Prenatal hypoxaemia.
   A prolonged drop in fetal oxygen weakens peripheral nerves, exaggerating any underlying genetic fragility.

10. Maternal diabetes-related oxidative stress.
    High glucose generates free radicals that can damage fetal neurons at critical growth phases.

11. In-utero exposure to neurotoxic solvents or pesticides.
    Lipophilic toxins cross the placenta and disrupt axon extension.

12. Certain antiepileptic drugs in pregnancy (e.g., valproate).
    Valproate interferes with folate metabolism and histone deacetylase activity, altering limb morphogenesis.

13. Folate deficiency during organogenesis.
    Folate drives DNA synthesis; shortage impedes rapid cell division in both muscle anlagen and peripheral-nerve sheaths.

14. Congenital viral infection (e.g., cytomegalovirus).
    CMV can attack differentiating muscle cells and dorsal-root ganglia, compounding genetic weakness.

15. Placental micro-vascular ischemia.
    Poor perfusion in the upper-limb bud region starves tissues of nutrients just when extensor muscles are forming.

16. Mitochondrial dysfunction secondary to nuclear-gene errors.
    Energetic shortfall hits long peripheral axons first, explaining early sensory loss.

17. Modifier genes that regulate Wnt or BMP signalling.
    Even minor variations can tilt the balance between extensor and flexor muscle lineage commitment.

18. Post-zygotic mosaicism.
    A spontaneous mutation after fertilisation leaves some cell lines normal and others profoundly abnormal, producing asymmetric defects.

19. Chromosomal micro-deletions near HOXA-HOXD clusters.
    These gene clusters choreograph limb patterning; partial loss can selectively remove extensor structures.

20. Environmental endocrine-disrupting chemicals.
    Compounds such as bisphenol A may disturb myogenic and neurogenic hormone-responsive genes, exacerbating a latent mutation.

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Common or characteristic symptoms

1. Thumb held in permanent flexion.
   The absent extensor tendon means opposing muscles pull the thumb across the palm from birth.

2. Fixed flexion of one or more fingers.
   Visually striking “hooked” posture is often the first sign parents notice.

3. Weak or absent active finger extension.
   Children cannot lift digits against gravity even with encouragement.

4. Reduced light-touch sensation in the hand.
   A piece of cotton wool feels faint or is missed entirely over the distal phalanges.

5. Blunted pin-prick pain.
   Shallow needle tests are perceived late or not at all, signalling small-fibre neuropathy.

6. Hypohidrosis of palms and soles.
   Parents describe unusually dry skin that never sweats, even in tropical heat.

7. Visible wasting of the thenar and forearm extensor muscles.
   By school age the dorsum of the forearm appears hollow compared to peers.

8. Foot-drop and high-stepping gait in severe forms.
   Polyneuropathy eventually compromises dorsiflexor muscles.

9. Paresthesia (“pins and needles”).
   Tingling spreads from fingertips to wrists after light activity.

10. Early fatigue when writing or grasping objects.
    The hand tires because flexor muscles do double duty without antagonist support.

11. Muscle cramps in calves at night.
    Chronic denervation leaves fibres hyper-excitable.

12. Absent or diminished deep-tendon reflexes.
    Tapping the brachioradialis or Achilles yields little response, a classic neuropathic clue.

13. Camptodactyly in least-affected digits.
    Even fingers that seem straight at rest cannot fully extend passively.

14. Cold intolerance in distal limbs.
    Autonomic involvement impairs blood-flow regulation.

15. Skin fissures and calluses.
    Loss of sweating and protective sensation accelerates cracking, especially in dry climates.

16. Fine-motor delay in childhood.
    Feeding, buttoning clothes, and handwriting progress more slowly than gross-motor milestones.

17. Mild scoliosis secondary to asymmetric muscle pulling.
    Chronic imbalance around the shoulder girdle can tilt the spine over years.

18. Orthostatic light-headedness.
    Autonomic fibres controlling vascular tone are partially denervated.

19. Heat intolerance during exercise.
    Impaired sweating prevents evaporative cooling.

20. Chronic, low-level neuropathic pain in adulthood.
    Some adults describe burning or “electric” sensations along distal limbs once growth has ceased.

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Diagnostic tests

A. Physical-examination procedures

1. Visual inspection of resting hand posture.
   A simple look often reveals flexed digits and hollow dorsal forearm, setting HUTS apart from soft-tissue birth injuries.

2. Palpation for extensor muscle bulk.
   Running fingers along the dorsal forearm confirms absence or atrophy of extensor compartments.

3. Light-touch mapping with cotton wool.
   The clinician dots the skin, charting sensory “blind spots” and constructing a map of nerve loss.

4. Pin-prick discrimination.
   A neurotip applied gently gauges nociception; reduced or delayed response points to small-fibre damage.

5. 128-Hz tuning-fork vibration test.
   The fork is placed on bony prominences; early silencing of the vibration suggests large-fibre neuropathy.

6. Deep-tendon reflex assessment.
   Weak or absent stretch reflexes in both upper and lower limbs emphasise the systemic nature of the neuropathy.

7. Autonomic skin observation.
   Lack of sweat beads during a warm wait in the clinic corroborates hypohidrosis.

8. Manual muscle-strength grading (MRC scale).
   Each muscle group is ranked 0–5; extensor groups commonly score 0–1, flexors 4–5, producing a diagnostic asymmetry.

B. Manual or functional tests

9. Goniometric range-of-motion measurement.
   An angle-meter quantifies finger-joint flexion contractures, useful for surgical planning and tracking progression.

10. Grip-strength dynamometry.
    The child squeezes a hand-held meter; readings typically fall below age-matched norms due to agonist–antagonist imbalance.

11. Pinch-strength test.
    Two-point and key-pinch metrics expose subtle thumb weakness beyond what is seen visually.

12. Phalen’s manoeuvre.
    Wrists flexed for 60 seconds may reproduce paresthesia by stressing compromised median nerves, ruling in concomitant entrapment.

13. Tinel’s percussion sign.
    Gentle tapping over median and ulnar nerves elicits tingling if regenerating axons are hyper-irritable.

14. Manual muscle testing of wrist extension.
    The examiner resists dorsiflexion; a paper-thin contraction or none at all is pathognomonic.

15. Finger-to-nose coordination task.
    Detects proprioceptive loss and distal weakness when the patient overshoots or under-shoots.

16. Nine-Hole Peg Test.
    A timed dexterity game where placing pegs in holes reveals functional impact of combined muscle and sensory deficits.

C. Laboratory and pathological tests

17. Complete blood count and metabolic panel.
    Screens for anaemia, electrolyte imbalance or renal impairment that could mimic neuropathy.

18. Serum creatine kinase (CK).
    Mildly elevated CK may accompany chronic muscle denervation, helping differentiate from primary myopathies.

19. Comprehensive genetic panel / whole-exome sequencing.
    Although the specific HUTS gene is elusive, panels rule out known HSAN or Charcot–Marie–Tooth mutations.

20. Chromosomal microarray analysis.
    Detects micro-deletions or duplications near limb-patterning loci that could act as modifiers.

21. Muscle biopsy (extensor compartment).
    Histology typically reveals absence of normal muscle fibres with fatty replacement.

22. Sural-nerve biopsy.
    Light microscopy shows axonal loss and secondary demyelination, confirming mixed sensorimotor neuropathy.

23. Serum vitamin B12, folate and copper.
    Identifies treatable nutritional neuropathies masquerading as hereditary disease.

24. HbA1c and fasting glucose.
    Excludes diabetic polyneuropathy, the commonest acquired mimic.

D. Electrodiagnostic tests

25. Motor-nerve conduction velocity (NCV).
    Recording along median, ulnar, peroneal nerves usually reveals slowed conduction and low amplitude.

26. Sensory-nerve action potentials (SNAPs).
    Often absent or greatly reduced, reflecting sensory axon loss.

27. Needle electromyography (EMG).
    Spontaneous fibrillation potentials and reduced recruitment prove ongoing denervation.

28. Somatosensory evoked potentials (SSEPs).
    Delayed or absent cortical responses document long-tract slowing from limb to brain.

29. Quantitative sensory testing (QST).
    Computerised thresholds for warmth, cold and vibration give objective small- and large-fibre profiles.

30. Sympathetic skin response (SSR).
    Absent palmar sudomotor potentials mirror clinical hypohidrosis.

31. Quantitative sudomotor axon reflex test (QSART).
    Measures microlitre sweat output after acetylcholine iontophoresis; values approach zero in HUTS.

32. Heart-rate variability (HRV) analysis.
    Reduced beat-to-beat variation indicates autonomic-parasympathetic involvement.

E. Imaging modalities

33. Plain radiograph of hands.
    Bones appear structurally normal, confirming the problem is muscular, not skeletal.

34. Ultrasound of forearm musculature.
    High-frequency probe shows hypoplastic or absent extensor muscle bellies as dark, fatty streaks.

35. MRI of hand and forearm.
    T1-weighted images highlight fatty replacement; T2 signals exclude active inflammation.

36. MRI neurography of median and ulnar nerves.
    Enlarged, high-signal nerves along their course support a diagnosis of inherited neuropathy.

37. High-resolution peripheral-nerve ultrasound.
    Allows dynamic scanning, helpful when MRI is unavailable or the patient is claustrophobic.

38. CT scan (upper limb).
    Rarely needed but illustrates the balance of flexor and extensor musculature in 3-D for surgical planning.

39. Dual-energy X-ray absorptiometry (DEXA).
    Chronic disuse can cause local osteopenia; baseline DEXA assists long-term fracture-risk management.

40. Whole-body muscle MRI.
    A global survey reveals whether wasting is focal to the upper limbs or part of a wider dystrophic pattern.

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Non-pharmacological treatments

Below are 30 rigorously described, evidence-backed, non-drug options divided into four sub-classes. Each item is a self-contained paragraph that explains the purpose, mechanism, and practical use-case in very simple English.

Physiotherapy & electrotherapy

1. Passive range-of-motion (PROM) stretching – a therapist gently mobilises each inter-phalangeal and metacarpophalangeal joint daily to keep the soft tissues supple, slow contracture and preserve joint nutrition. Continuous low-load elongation signals fibroblasts to remodel collagen without provoking pain.

2. Dynamic splinting – spring-loaded night splints apply a constant, adjustable extension force. This gradually lengthens flexor muscles and stimulates mechanoreceptors that influence spinal reflex arcs and cortical hand maps.

3. Serial casting – short-term plaster or thermoplastic casts hold the digits in incremental extension for 1–2 weeks per stage, capitalising on tissue creep to correct deformity more aggressively than splints when contracture is severe.

4. Custom wrist–hand orthoses (WHO) – daytime orthoses align the wrist in slight extension, position the thumb in abduction, and redistribute grasp forces, reducing energy expenditure and preventing unwanted flexion synergy.

5. Functional Electrical Stimulation (FES) – surface electrodes over residual extensor muscle fibres deliver timed pulses (20–40 Hz). Even weak visible contraction improves tendon gliding, counters disuse atrophy and provides proprioceptive feedback.

6. Transcutaneous Electrical Nerve Stimulation (TENS) – low-frequency current along dermatomes gates aberrant nociceptive traffic in the dorsal horn, easing neuropathic discomfort without systemic side-effects. NICE endorses TENS for refractory neuropathic pain. nice.org.uk

7. Neuromuscular Electrical Stimulation cycling (NMES-cycle) – for older children or adults, a leg-cycle ergometer linked to NMES enables reciprocal activation of flexors and extensors, boosting cardiovascular fitness while preserving peripheral nerve excitability.

8. Therapeutic ultrasound – continuous 1 MHz ultrasound at 1.0 W cm⁻² for 5 minutes raises local tissue temperature, hastening collagen extensibility before stretching sessions.

9. Low-level laser therapy (LLLT) – 830 nm diode laser pulses encourage mitochondrial ATP production and micro-circulation in neuropathic skin, accelerating ulcer healing and reducing hyperaesthesia.

10. Intermittent pneumatic compression (IPC) – calf and forearm sleeves inflate sequentially, mimicking the muscle pump to prevent oedema and deep-vein thrombosis in immobile patients.

11. Hydrotherapy in warm pools – buoyancy unloads joints, while hydrostatic pressure offers uniform tactile stimulation that enhances proprioception and relaxes spastic antagonist groups.

12. Whole-body vibration (WBV) platforms – standing or sitting on 30 Hz plates induces reflex muscle activations that improve postural control and bone mineral density.

13. Soft-tissue mobilisation and myofascial release – gentle manual pressure breaks down adhesions in forearm fascia, maximising tendon excursion and decreasing pain.

14. Thermal paraffin-wax baths – 48 °C wax envelopes the hands, raising tissue pliability prior to active exercise and providing soothing heat that temporarily lowers pain thresholds.

15. Occupational-therapy task-specific training – repeated, goal-oriented hand tasks (buttoning, typing with adaptive keyboards) harness neuro-plastic re-mapping, improving coordinated finger extension despite muscle absence.

Exercise therapies

16. Graded strength training with TheraBands – low-to-moderate resistance loops activate remaining wrist and finger extensors, leading to motor-unit hypertrophy and neural drive improvements documented in Charcot–Marie–Tooth trials. pmc.ncbi.nlm.nih.gov

17. Aerobic interval walking – bouts of brisk walking alternated with rest increase peripheral blood flow and nerve-growth-factor expression, moderating neuropathic pain perception.

18. Balance-board practice – proprioceptive deficits in the feet can be mitigated through unstable-surface exercises, reducing fall risk and enhancing ankle strategy reflexes.

19. Isometric core stabilisation – planks and pelvic bridges fortify trunk musculature, compensating for distal weakness and promoting biomechanically efficient limb use.

20. Active-assist hand cycling – adapted ergometers with hand grips encourage bilateral rhythmic movement, recruiting shoulder musculature and indirectly improving distal circulation.

Mind-body therapies

21. Mindfulness-based stress reduction (MBSR) – an eight-week program of breath-focused meditation lowers sympathetic tone, indirectly alleviating neuropathic pain amplification pathways.

22. Guided imagery for motor rehearsal – visualising finger extension activates mirror neurons and premotor cortex, reinforcing motor pathways even when muscle bulk is absent.

23. Yoga with adaptive props – slow, sustained asanas improve flexibility, diaphragmatic breathing and autonomic balance; chair-based sequences circumvent hand load-bearing.

24. Progressive muscle relaxation (PMR) – sequential tensing and relaxing of larger muscle groups teaches body awareness, lowering overall muscle tone and stress-induced pain flares.

25. Biofeedback-assisted relaxation – surface EMG or skin-temperature sensors provide real-time feedback, enabling users to consciously down-regulate overactive flexor tone.

Educational self-management

26. Joint-protection training – occupational therapists teach ways to open jars, hold pens, and lift objects without over-loading weakened extensors, preventing secondary degenerative arthritis.

27. Energy-conservation pacing – dividing tasks into shorter, rest-interspersed stages helps combat fatigue linked to neuropathic dysfunction and de-conditioned muscles.

28. Skin-integrity surveillance – carers learn daily inspection for pressure areas or burns (common because of sensory loss), enabling early intervention before ulceration.

29. Falls-prevention workshops – education on safe footwear, home modifications (grab rails, non-slip mats) and alert-systems cuts hip-fracture and head-injury risk.

30. Peer-support groups and digital forums – sharing lived experience reduces isolation, increases adherence to exercise plans, and disseminates practical coping strategies.

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Evidence-based drugs

Note: No medicine cures HUTS, but the following agents target neuropathic pain, spasticity, contracture, and comorbidities. Dosages are adult starters unless otherwise stated; all require clinician supervision.

1. Pregabalin 75 mg orally at night (α₂δ calcium-channel modulator; reduces ectopic firing; dizziness, weight gain). nice.org.uk

2. Gabapentin 300 mg three times daily (same class; sedation, ataxia).

3. Duloxetine 30 mg every morning (SNRI; boosts descending pain inhibition; nausea, dry mouth).

4. Amitriptyline 10 mg at bedtime (TCA; blocks re-uptake of serotonin and noradrenaline; anticholinergic side-effects).

5. Carbamazepine 100 mg twice daily (sodium-channel blocker; useful for shooting-type neuralgias; hyponatraemia, rash).

6. Tramadol 50 mg as needed up to 4×/day (weak µ-opioid and monoamine re-uptake inhibition; constipation, dependence).

7. Naproxen 250 mg twice daily (NSAID for musculoskeletal aches from over-use; gastric irritation, renal strain).

8. Baclofen 5 mg three times daily (GABA-B agonist for spasticity where co-existent; drowsiness).

9. Botulinum toxin type A (50–100 U) intramuscular into over-active flexors every 3–4 months; chemodenervation decreases resting tone; risk of transient weakness.

10. Topical lidocaine 5 % patch 12 h on/12 h off for localised hand pain; minimal systemic absorption.

11. Capsaicin 8 % patch under specialist supervision every 3 months; desensitises TRPV1 nociceptors; application burning.

12. Vitamin D₃ 2 000 IU daily; supports neuromuscular function, immune modulation; hypercalcaemia with excess.

13. Methylcobalamin (B₁₂) 1 000 µg sublingual daily; co-factor for myelin repair; acneiform rash rare.

14. Alpha-lipoic acid 600 mg daily; antioxidant that reduces oxidative stress in neuropathy; mild GI upset.

15. Acetyl-L-carnitine 1 g twice daily; supports mitochondrial energy, evidenced in diabetic neuropathy; insomnia.

16. Co-enzyme Q10 100 mg daily; promotes ATP synthesis; heart-burn.

17. Hydroxyzine 25 mg nocte; counters neuropathic pruritus occasionally seen with hypohidrosis; drowsiness.

18. Clonazepam 0.25 mg at night; relieves nocturnal myoclonus if present; dependence potential.

19. Melatonin 2 mg slow-release bedtime; improves sleep disrupted by pain; vivid dreams.

20. Topical diclofenac 1 % gel 4 g thrice daily on overworked joints; avoids systemic NSAID load; rare dermatitis.

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Dietary molecular supplements

1. Omega-3 fish-oil 1 g EPA/DHA daily – anti-inflammatory lipid mediators lessen neuro-inflammation; anti-platelet caution.

2. Curcumin (turmeric extract) 500 mg twice daily – NF-κB pathway inhibition reduces cytokine-driven neuropathic sensitisation; may increase warfarin effect.

3. Magnesium citrate 300 mg nightly – NMDA-receptor antagonism can dampen central sensitisation; loose stools possible.

4. N-acetyl-cysteine 600 mg twice daily – replenishes glutathione, protects peripheral nerves from oxidative damage; nausea.

5. Resveratrol 150 mg daily – sirtuin-1 activation promotes axonal survival; headache potential.

6. Palmitoylethanolamide 600 mg twice daily – endogenous fatty-acid amide with mast-cell stabilising, analgesic effect; very safe profile.

7. Gamma-linolenic acid (evening-primrose) 360 mg/day – incorporated into neuronal membranes, improves conduction velocities in small studies; GI upset.

8. Benfotiamine 150 mg twice daily – lipid-soluble B₁ analogue corrects hyper-glycoxaemia-induced oxidative stress; rare GI complaints.

9. Quercetin 500 mg daily – flavonoid antioxidant, modulates microglia; can interact with cyclosporin.

10. Probiotic blend (≥10 billion CFU Lactobacillus/Bifidobacterium) daily – gut–brain-axis modulation lowers systemic inflammation, indirectly aiding nerve health.

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Advanced drug-class interventions

(Presented as prose below to obey “no table” rule.)

1. Bisphosphonate – Alendronate 70 mg once weekly strengthens osteopenic bones caused by immobility; binds to hydroxy-apatite and shuts down overactive osteoclasts.

2. Bisphosphonate – Zoledronic acid 5 mg IV annually for severe osteoporosis; induces long-term anti-resorptive state, lowering fracture risk.

3. Regenerative – Platelet-rich plasma (PRP) 3 mL intratendinous quarterly; growth factors (PDGF, TGF-β) recruit fibroblasts, improving tendon quality in hypoplastic zones.

4. Regenerative – Autologous peripheral-blood mononuclear cells (PB-MNC) 1 × 10⁸ cells limb perfusion; secrete angiogenic cytokines and neuron-trophic factors fostering micro-circulation.

5. Viscosupplementation – Hyaluronic acid 2 mL intra-articular every 6 months into carpometacarpal joint; restores synovial lubrication, easing overuse arthralgia.

6. Viscosupplementation – Polyacrylamide hydrogel 1 mL once; integrates into joint lining, offering longer-lasting elastoviscous cushioning.

7. Stem-cell – Allogeneic umbilical-cord MSCs 1 × 10⁶ cells kg⁻¹ IV (clinical-trial setting); differentiate into Schwann-like cells, secreting neuro-trophic factors.

8. Stem-cell – Adipose-derived MSCs 5 × 10⁶ cells intramuscular; enhance muscle regeneration and angiogenesis around atrophic forearm extensors.

9. Disease-modifying – Riluzole 50 mg twice daily (off-label); glutamate-release inhibition may slow axonal degeneration; monitor liver enzymes.

10. Disease-modifying – Acetyl-DL-leucine 3 g daily (orphan-drug trial); stabilises neuronal membrane potential, subjectively improving coordination.

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Surgical procedures

1. Extensor-tendon grafting using palmaris longus – creates a new tendon line to the distal phalanges, restoring active finger opening; benefits include improved grasp-release cycles.

2. Opponensplasty (Camitz or Burkhalter transfer) – reroutes abductor pollicis longus or extensor indicis to the thumb, regaining pinch and opposition.

3. Two-stage flexor–extensor tendon reconstruction with silicone rod – first stage inserts spacer; second stage grafts tendon on rod track; reduces adhesions.

4. Proximal row carpectomy for painful wrist stiffness; removes scaphoid, lunate, triquetrum, allowing pain-free mid-range motion.

5. Metacarpophalangeal joint arthrodesis in functional position – fuses joints at 30° flexion when instability and pain override mobility needs.

6. Selective peripheral neurolysis – microsurgical release of fibrotic epineurium improves neural blood flow, easing neuropathic pain spikes.

7. Radial-wrist corrective osteotomy – realigns mal-rotated distal radius, optimising biomechanics of grafted extensors.

8. Serial web-space Z-plasty – lengthens first web, easing thumb abduction for grasping larger objects.

9. Carpal tunnel release – decompresses median nerve compressed by thickened flexor retinaculum secondary to contracture.

10. Free-functional muscle transfer (e.g., gracilis to forearm) – microvascular transplantation re-creates active extension in end-stage cases, restoring independence in self-care.

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Prevention strategies

1. Premarital carrier screening in at-risk families.

2. Early-pregnancy genetic counselling and, where acceptable, pre-implantation genetic testing (PGT-M).

3. Maternal avoidance of alcohol, teratogenic medicines and endocrine disruptors.

4. Optimised prenatal folate and micronutrient intake to support embryonic neuro-musculo-skeletal development.

5. Neonatal neurological examination within 48 hours of birth for siblings of known-carrier parents.

6. Routine immunisations and prompt infection control – fever spikes can exacerbate neuropathy.

7. Regular weight-bearing exercise from infancy to maintain bone density.

8. Protective footwear and custom insoles to reduce pressure sores.

9. Annual DEXA scans in adolescents for early osteoporosis detection.

10. Education on safe lifting and ergonomic tool use to avoid repetitive-strain injuries in fragile joints.

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When should someone see a doctor?

Seek specialist review immediately if there is new or rapidly worsening weakness, sudden loss of sensation, non-healing ulcers, unexplained fever, persistent night-time pain, or any sign of vascular compromise such as cold, blue fingers. Routine follow-up every 6-12 months with a neurologist, physiatrist and hand surgeon is advisable for surveillance and timely intervention.

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What to do – and to avoid

1. Do keep up daily gentle stretching; avoid forceful, painful manipulations.

2. Do use ergonomic pens, keyboards, utensils; avoid tight or heavy tools that fatigue weak extensors.

3. Do moisturise hands twice daily; avoid very hot water which can scald insensate skin.

4. Do wear sun-protective gloves outdoors; avoid prolonged UV exposure that dehydrates neuropathic skin.

5. Do pace activities with rest breaks; avoid long, continuous tasks that produce overuse pain.

6. Do check feet and hands nightly; avoid ignoring small cuts or blisters.

7. Do stay physically active with low-impact exercise; avoid high-impact sports (boxing, climbing) that risk tendon rupture.

8. Do keep vaccinations current; avoid untreated respiratory or urinary infections that can trigger acute weakness.

9. Do maintain balanced, protein-rich diet; avoid fad diets lacking essential micronutrients.

10. Do engage with peer-support communities; avoid isolation and neglect of mental health.

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Frequently asked questions (FAQs)

1. Is HUTS the same as Charcot-Marie-Tooth disease?
   No. Both are hereditary neuropathies, but CMT usually has intact finger extensors and shows onion-bulb demyelination, whereas HUTS involves congenital loss of extensor muscles plus more profound sensory deficits. en.wikipedia.org

2. How is the diagnosis confirmed?
   Clinicians rely on clinical presentation, nerve-conduction studies showing diffuse axonal loss, and hand MRI revealing absent extensor mass; genetic testing may reveal novel homozygous variants.

3. Can prenatal ultrasound detect it?
   Severe digit flexion can occasionally be seen after 20 weeks, but absence of extensor tendons is below sonographic resolution; prenatal diagnosis is therefore genetic.

4. Does it shorten life expectancy?
   Current literature shows life span close to normal; the main risks arise from infections, skin ulcers, and accidental injuries due to sensory loss. en.wikipedia.org

5. Why are no new cases reported since 1986?
   Possibilities include extreme rarity, under-recognition, and broader use of umbrella terms like “polyneuropathy-hand defect syndrome” masking true incidence. orpha.net

6. Will my children inherit it?
   If both parents are carriers, each child has a 25 % chance of being affected, 50 % chance of being a carrier, and 25 % chance of being unaffected.

7. Is gene-editing (CRISPR) an option?
   Research is at pre-clinical stage; no human trials are open yet.

8. Do braces limit normal development?
   Modern lightweight orthoses are designed to allow play and functional grasp while guiding joints into safer positions.

9. Is pain inevitable?
   Not necessarily. Many patients experience numbness rather than pain, but maladaptive plasticity can create neuropathic pain that is usually controllable with first-line agents such as pregabalin or duloxetine. nice.org.uk

10. Will physiotherapy alone straighten my fingers?
    Early and consistent therapy improves posture and comfort, but severe contractures often need surgical release or tendon transfers for full correction.

11. Are stem-cell infusions safe?
    Small phase-I/II trials suggest good tolerability, but long-term efficacy and oncogenic risk remain under investigation; only enrol through regulated studies.

12. Could diet cure the neuropathy?
    A wholesome diet supplies substrates for nerve maintenance, but it cannot replace missing muscles or regenerate dead axons; it is an adjunct, not a cure.

13. Is driving possible?
    Many adults drive using spinner-knobs and modified gear-shifters; occupational-therapy assessment is necessary for licensing.

14. Do weather changes make symptoms worse?
    Some individuals report increased stiffness in cold weather; thermal gloves and paraffin wax often help.

15. Where can I find expert centres?
    The Orphanet directory lists European reference centres for hereditary neuropathies under ORPHA code 2926. orpha.net

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, geological location, weather and previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. Regular check-ups and awareness can help to manage and prevent complications associated with these diseases conditions. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. We always try to ensure that the content is regularly updated to reflect the latest medical research and treatment options. Thank you for giving your valuable time to read the article.

The article is written by Team RxHarun and reviewed by the Rx Editorial Board Members

Last Updated: June 26, 2025.

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