Pediatric Annals

Hereditary Motor and Sensory Neuropathies

Geoffrey Miller, MA, MD, MRCP, FRACP; Robert C Vannucci, MD

Abstract

The hereditary motor neuropathies comprise a heterogeneous group which, apart from the inherited recurrent focal neuropathies, is characterized by its symmetrical nature, insidious onset, and slow progression. Until the primary genetic and biochemical bases of these disorders are known, they will remain classified according to clinical, genetic, and pathologic features (Table 1). There also exists a rare group of neuropathies characterized by selective involvement of peripheral sensory and autonomie neurons (Table 2).1 These disorders, which are usually autosomal recessive, are manifest by varying degrees of autonomie dysfunction or insensitivity to pain and temperature, occasionally with striking self-mutilation.2 The spinal muscular atrophies and those diseases which clinically involve different parts of the nervous system, such as Retsum's disease, the leukodystrophies, and Friedreich's ataxia, will not be considered here.

CONGENITAL MOTOR AND SENSORY NEUROPATHIES

These disorders have their onset in the neonatal period or early infancy (Table 1 ). * Affected infants are weak, hypotonie, and areflexic. The weakness may be predominantly distal in distribution with associated muscle wasting, as well as swallowing and respiratory difficulties. Marked motor delay usually follows. The most severe type is associated with complete absence of peripheral myelin sheaths with no evidence of demyelination or remyelination (onion-bulb formation) on nerve biopsy. Clinically, there is extreme weakness with respiratory distress, and early death is frequent. Motor nerve conduction velocities are very slow. Clinical features are less severe in the neuronal type of congenital neuropathy. In this form, sural nerve biopsy shows a lack of large myelinated fibers, and motor nerve conduction velocities are only moderately slowed. Inheritance is autosomal recessive. In other types of congenital hypomyelination neuropathy, clinical manifestations are variable. Motor nerve conduction velocities are extremely slow, and nerve biopsy shows partial hypomyelination with atypical onion-bulb formation. Some of the latter group may represent early presentations of the hypertrophie form of Charcot-Marie-Tooth or Dejerine-Sottas disease or he due to decreased myelin production hy abnormal Schwann's cells.

Table

Hereditary Neuropathy with Liability to Pressure Palsies (Tomaculous Neuropathy)

This is an autosomal dominant disorder which is characterized by recurrent painless focal neuropathies. The neuropathies are often associated with relatively minor episodes of trauma or compression, such as sleeping on a limb, and the associated weakness can last for weeks. Nerves most likely to be compressed include the radial, ulnar, and peroneal nerves. Although asymptomatic, careful examination may reveal signs of a more diffuse peripheral neuropathy, particularly in older patients. On nerve conduction study, generalized, moderate slowing of the nerve conduction velocities is found along with a reduction and dispersion of the action potential amplitude. Sural nerve biopsy shows focal thickening (tomacufous) of the myelin sheath.

1. Axelrod FB, Pearson J: Congenital sensory neuropathies. Diagnostic distinction from familial dysautonomia. Am J Dis Child 1984; 138:947-954.

2. Dyck PJ: Neuronal atrophy and degeneration predominatly affecting peripheral sensory and autonomic neurons, in Dyck PJ. Thomas PK. Lambert EH. et al (eds): Peripheral Neurophaty. Philadelphia, W.B. Saunders Co., 1984, pp 1557-1599.

3. Lütsche J. Vassella F. Boltshauser E, et al: Heterogeneity of congenital motor and sensory neuropathies. Neuropediatrics 1985; 16:33-38.

4. Ouvrier RA, McLeod JG, ConchmT: The hypertrophic forms of hereditary motor and sensory neuropathy. Brain 1987; 110:121-148.

5. Ouvrier RA, McLeod IG. Morgan GJ, er al: Hereditary motor and sensory neuropathy of neuronal type with onset in early childhood. J Neurol Sci 1981; 51:181-197.

6. Windebank AJ. Inherited recurrent local neuropathies. In Dyck PJ. Thomas PK. Lambert EH, el al (eds): Peripheral Neuropathy Philadelphia, W.B. Saunders Co., 1984, pp. 1656-1679.

TABLE 1

Some Hereditary Motor Neuropathies

TABLE 2

Hereditary Sensory and Autonomic Neuropathies (HSAN)…

The hereditary motor neuropathies comprise a heterogeneous group which, apart from the inherited recurrent focal neuropathies, is characterized by its symmetrical nature, insidious onset, and slow progression. Until the primary genetic and biochemical bases of these disorders are known, they will remain classified according to clinical, genetic, and pathologic features (Table 1). There also exists a rare group of neuropathies characterized by selective involvement of peripheral sensory and autonomie neurons (Table 2).1 These disorders, which are usually autosomal recessive, are manifest by varying degrees of autonomie dysfunction or insensitivity to pain and temperature, occasionally with striking self-mutilation.2 The spinal muscular atrophies and those diseases which clinically involve different parts of the nervous system, such as Retsum's disease, the leukodystrophies, and Friedreich's ataxia, will not be considered here.

CONGENITAL MOTOR AND SENSORY NEUROPATHIES

These disorders have their onset in the neonatal period or early infancy (Table 1 ). * Affected infants are weak, hypotonie, and areflexic. The weakness may be predominantly distal in distribution with associated muscle wasting, as well as swallowing and respiratory difficulties. Marked motor delay usually follows. The most severe type is associated with complete absence of peripheral myelin sheaths with no evidence of demyelination or remyelination (onion-bulb formation) on nerve biopsy. Clinically, there is extreme weakness with respiratory distress, and early death is frequent. Motor nerve conduction velocities are very slow. Clinical features are less severe in the neuronal type of congenital neuropathy. In this form, sural nerve biopsy shows a lack of large myelinated fibers, and motor nerve conduction velocities are only moderately slowed. Inheritance is autosomal recessive. In other types of congenital hypomyelination neuropathy, clinical manifestations are variable. Motor nerve conduction velocities are extremely slow, and nerve biopsy shows partial hypomyelination with atypical onion-bulb formation. Some of the latter group may represent early presentations of the hypertrophie form of Charcot-Marie-Tooth or Dejerine-Sottas disease or he due to decreased myelin production hy abnormal Schwann's cells.

Table

TABLE 1Some Hereditary Motor Neuropathies

TABLE 1

Some Hereditary Motor Neuropathies

HEREDITARY MOTOR AND SENSORY NEUROPATHY (HMSN)

HMSN Type I (Hypertrophie Form of Charcot'Marie-Tooth Disease)

This autosomal dominant disorder shows great variability in clinical expression.4 Presentation is usually in late childhood hut may present earlier. Conversely, some individuals remain asymptomatic well into adulthood; diagnosis in these individuals can he established only hy nerve conduction studies. In symptomatic children, initial signs consist of motor delay and clumsy gait. Weakness begins in the distal leg muscles, particularly the intrinsic foot muscles, the peroneal and the anterior tibia! muscles, which leads to pes cavus, hammer toes, and toot drop. Muscle wasting occurs in a distal distribution. Progression is slow and only after many years do the distal upper limbs become involved. Some individuals eventually show wasting and clawing ot the hands and palpable superficial nerves of the head and neck. Sensory changes are usually slight. Postural tremor and ataxia are frequent features. Diminution of the Achilles tendon reflexes is usual, but decreased deep tendon reflexes at other sites are variable. Diagnosis is suspected from the clinical picture and confirmed by the presence of slow motor nerve conduction velocities (<50% of normal) in the patient and one parent. Elevated cetebrospinal fluid protein is characteristic of older patients. Sural nerve biopsy shows onion-bulb formation which increases with age.

HMSN Type II (Neuronal Form of Charcot-MariC'Tooth Disease)

This disorder is also autosomal dominant. An autosomal recessive type with early onset has also been described.5 The clinical features are similar to HMSN type I but are milder and deformity, if it occurs, does so later. Slow progression and variable distal sensory loss are features. Motor nerve conduction velocities are usually normal or only slightly decreased but occasionally are difficult to obtain, particularly in the lower extremities.

HMSN Type III (Dejerine-Sottas Disease)

This is an autosomal recessive or sporadic disorder, which characteristically ptesents in early childhood with hypotonia, weakness, and delayed motor milestones. As in HMSN type I, the lower extremities are predominantly affected and eventually show distal wasting. Lower facial weakness also occurs and leads to a characteristic facial affect with prominent pouting lips ( lèvres de tapir). The greatet auricular and cervical nerves are usually palpable. Ataxia is a prominent feature and may be more disabling than the decreased muscle power. Sensory loss can be found, particularly involving vibration and position sense and, to a lesser degree, touch and superficial pain sensation. Loss of deep tendon reflexes is more likely than in HMSN type I, and motor nerve conduction velocities are extremely slow. Findings on sural nerve biopsy are similar to but more marked than those seen in HMSN type I.

INHERITED RECURRENT FOCAL NEUROPATHY

As opposed to the hereditary motor and sensory neuropathies - which produce symmetrical weakness, are of insidious onset, and are slowly progressive - these disorders are focal in distribution and acute in onset. 6 They may be recurrent with variable degrees of resolution.

Inherited Brachial Plexus Neuropathy

Although onset is usually in the second or third decade, this autosomal dominant disorder may occur in late childhood. Weakness is preceded by upper exttemity pain of one-week duration. Characteristically, the limb is immobile as shoulder movement exacerbates the pain. Pain may mask the muscle weakness which appears after a few days and progresses thereafter. The weakness can be present for weeks to months and sometimes affects all of the brachial plexus innervated muscles, although there is a predilection for the proximal groups. The lumbosacral plexus and cranial nerves can be involved but not at the same time as the upper extremity. Recovery is slow but usually complete. However, some motot deficit can remain after repeated episodes. Precipitating factors have been described, including exercise, pregnancy, and delivery.

Table

TABLE 2Hereditary Sensory and Autonomic Neuropathies (HSAN)

TABLE 2

Hereditary Sensory and Autonomic Neuropathies (HSAN)

Hereditary Neuropathy with Liability to Pressure Palsies (Tomaculous Neuropathy)

This is an autosomal dominant disorder which is characterized by recurrent painless focal neuropathies. The neuropathies are often associated with relatively minor episodes of trauma or compression, such as sleeping on a limb, and the associated weakness can last for weeks. Nerves most likely to be compressed include the radial, ulnar, and peroneal nerves. Although asymptomatic, careful examination may reveal signs of a more diffuse peripheral neuropathy, particularly in older patients. On nerve conduction study, generalized, moderate slowing of the nerve conduction velocities is found along with a reduction and dispersion of the action potential amplitude. Sural nerve biopsy shows focal thickening (tomacufous) of the myelin sheath.

REFERENCES

1. Axelrod FB, Pearson J: Congenital sensory neuropathies. Diagnostic distinction from familial dysautonomia. Am J Dis Child 1984; 138:947-954.

2. Dyck PJ: Neuronal atrophy and degeneration predominatly affecting peripheral sensory and autonomic neurons, in Dyck PJ. Thomas PK. Lambert EH. et al (eds): Peripheral Neurophaty. Philadelphia, W.B. Saunders Co., 1984, pp 1557-1599.

3. Lütsche J. Vassella F. Boltshauser E, et al: Heterogeneity of congenital motor and sensory neuropathies. Neuropediatrics 1985; 16:33-38.

4. Ouvrier RA, McLeod JG, ConchmT: The hypertrophic forms of hereditary motor and sensory neuropathy. Brain 1987; 110:121-148.

5. Ouvrier RA, McLeod IG. Morgan GJ, er al: Hereditary motor and sensory neuropathy of neuronal type with onset in early childhood. J Neurol Sci 1981; 51:181-197.

6. Windebank AJ. Inherited recurrent local neuropathies. In Dyck PJ. Thomas PK. Lambert EH, el al (eds): Peripheral Neuropathy Philadelphia, W.B. Saunders Co., 1984, pp. 1656-1679.

TABLE 1

Some Hereditary Motor Neuropathies

TABLE 2

Hereditary Sensory and Autonomic Neuropathies (HSAN)

10.3928/0090-4481-19890701-08

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