• Motor involvement is more prominent.
• Sensory and autonomic dysfunction is then added to the process.
• The classification of this disease group is quite complicated and intertwined. According to a classification method;
I. Hereditary neuropathies secondary to other diseases
II.
a. Hereditary motor sensory neuropathies (HMSN)
b. Distal hereditary motor neuropathies
c. Hereditary sensory autonomic neuropathies
III. Syndromic neuropathies including congenital hypomyelinating neuropathies
IV. Hereditary sensory neuropathies (Refsum's disease)
PERONEAL MUSCULAR ATROPHY(CHARCOT-MARIE-TOOTH DISEASE HMDN TYPE lla)
• This disease is the most common genetically determined neuropathy.
• It is inherited as an autosomal dominant. The gene product is peripheral myelin protein P22 (PMP22).
Clinical Findings
• Most patients are asymptomatic until late childhood or early adolescence.
The peroneal and tibial nerves are the earliest and most severely affected.
• Children with the disease are often described as clumsy, falling easily or tripping over their own legs. The onset of symptoms may be delayed up to the 5th decade.
• The muscles in the anterior compartment of the legs may be wasted and the legs have a characteristic, stork-like appearance.
• Muscle atrophy is accompanied by progressive weakness in ankle dorsiflexion and eventually drop foot. The process is bilateral but can be somewhat asymmetrical. As a result of denervation of the intrinsic foot muscles, pes cavus may develop, further destabilizing the gait.
• Atrophy of the forearm and hand muscles is usually not as severe as in the lower extremities, but in advanced cases, contractures of the wrists and fingers can cause clawed hands.
Proximal muscle weakness is a late symptom and is usually mild. Axial muscles are not involved.
• Sensory involvement mainly affects large myelinated nerve fibers that carry proprioceptive and vibration sense. However, the threshold for pain and temperature may also increase. Some children complain of chills or burning sensations in the legs, but pain is rare.
Motor involvement is more prominent than sensory involvement.
• Paleness of the feet and coldness despite warming indicates poor vasomotor control and autonomic findings.
• Nerves are usually enlarged enough to be palpated. Distally, DTRs are lost. Cranial nerves are not involved.
• Sphincter control is well maintained. Autonomic neuropathy does not affect the heart, gastrointestinal tract, or bladder.
• Intelligence level is normal.
• Davidenkow syndrome is a variant of HMSN with a scapuloperoneal distribution.
Diagnosis
• Electromyography (EMG) and muscle biopsy are often not required for diagnosis; however, they show denervation and reinnervation cycles. Motor and sensory nerve conduction velocity was decreased in EMG.
• Serum creatine kinase (CPK) level is normal.
• Cerebrospinal fluid (CSF) protein may be elevated, but no cells are seen in the CSF.
• Sural nerve biopsy is diagnostic. The number of large and medium-sized myelinated fibers decreases, collagen increases, and the cytoplasm of the proliferating Schwann cells creates the appearance of onion skin around the accents. This pathological finding is called interstitial hypertrophic neuropathy.
• Molecular genetic diagnosis can be made from peripheral blood.
Treatment
• Supportive treatment is given. There is no medical treatment that stops or slows the progression. However, carbamazepine and phenytoin can be used for ankle stabilization and patchy paresthesias.
OTHER hereditary motor-sensory neuropathies
• Peroneal muscular atrophy (axonal type)
OD is inherited, progresses more slowly
• Congenital hypomyelinating neuropathy and Dejerine-sottas disease (HMDN type 3)
OD is inherited, much more severe, begins in early infancy and progresses rapidly, with hypotonia, respiratory and feeding difficulties. There is congenital insensitivity to pain, cranial nerve involvement, no DTR. Arthrogryposis is common.
Dejenrine-sottas disease progresses more slowly and its onset is usually before 5 years of age.
In the sural nerve biopsy, there is an appearance of onion skin.
• Roussy-Levy syndrome
It is accompanied by cerebellar defect, similar to Friedrich's ataxia, but without cardiomyopathy.
• Refsum's disease (hereditary sensory neuropathy type 4)
It starts between the ages of 4-7. Phytanic acid level increased. Ataxia, progressive neurosensory hearing loss, retinitis pigmentosa and night blindness, ichthyosis, hepatic dysfunction are seen. Life expectancy can be normal with diet and periodic plasma exchange.
• Fabry disease
• Giant axonal neuropathy
OR passes, and progressive mixed peripheral neuropathy and central nervous system white matter degeneration are seen in early childhood. Ataxia accompanies nystagmus.
• Congenital hypomyelinating neuropathy
Myelination in peripheral motor and sensory nerves is abnormal. It is normal in MSS.
DTR is not taken, there is arthrogryposis.
• Tomaculosis neuropathy (hypermyelinating neuropathy)
OD passes, with excessive myelin production, nerve fibers thicken into sausage shape.
• Leukodystrophies