Rarely, spinocerebellar ataxias can present in infancy.314 When the SCA2 alleles contain more than 200 repeats, for example, SCA2 can present in infancy with hypotonia, developmental delay, dysphagia, and retinitis pigmentosa.42 Earlyonset is associated with a shorter survival, while the prognosis is relatively good with later onset, after age 20.343 Involvement of the inferior olivary nuclei is present.342 Intellectual deterioration and dementia may occur later in the course of the disease. Both autosomal dominant cerebellar ataxia types I and II are associated with optic atrophy and ophthalmoplegia.349,352 However, type II is distinguished by the presence of pigmentation macular dystrophy; this dystrophy includes early granularity and mottling that is later associated with pigmentary changes that gradually spread to the periphery, with late optic atrophy and attenuation of retinal vessels.238,308,405,745,866 Most cases become evident in adulthood, but a dominantly inherited form that is associated with retinal degeneration can present as early as the first year of life. The optic atrophy seen in some patients may be secondary to associated retinal degeneration or may occur primarily as part of the multisystem CNS atrophy seen on MR imaging in this condition.216,345,492,531,767 Unfortunately, detailed analysis of the prevalence of optic atrophy among the different genetic subtypes has not been performed,573 and the distinction between primary optic atrophy and optic atrophy secondary to retinal disease has not been analyzed.2,351,832

Autosomal dominant cerebellar ataxia type 2 (now termed SCA7) is the only type associated with pigmentary degeneration.67,309,692 The ADCA type II locus has been mapped to chromosome 3p12-p21, suggesting that this phenotype corresponds to a homogeneous genotype.309,365 The responsible gene for this new subtype of ADCA, termed SCA7, has been cloned.187 SCA7 (or ADCA type II) is caused by an unstable CAG repeat in the SCA gene. Larger expansions are associated with earlier onset, a more severe and rapid clinical course, and a higher frequency of decreased vision, ophthalmoplegia, extensor plantar responses, and scoliosis. The mutation is highly unstable, with an increase in repeats with paternal transmission, correlating with marked anticipation. This instability of transmission is more marked than with other SCA subtypes.

Friedreich ataxia is the most common genetic ataxia and the first known example of a trinucleotide repeat resulting in autosomal recessive disease.342 It is an autosomal recessive disorder characterized by the onset of progressive cerebellar ataxia, dorsal root ganglion degeneration, and corticospinal tract involvement, generally associated with muscular wasting. Most patients with Friedreich ataxia present with symptoms prior to age 25, with an average age at onset of 12.342

Key diagnostic features include progressive ataxia of the limbs and gait, extensor plantar responses, dysarthria, abnormal position and vibration sense and absent deep tendon reflexes in lower extremities, progressive scoliosis and pes

cavus, and hypertrophic progressive cardiomyopathy.513,840 MR imaging reveals a normal cerebellum with variable atrophy of the cervical spinal cord.

Friedreich ataxia results from defects on the frataxin gene on chromosome 9q13, resulting in an expansion of the GAA repeat in the first intron in over 90% of cases.918 Because of the clinical resemblance to ataxia with Vitamin E deficiency (which responds to vitamin E supplementation), it is important to confirm this condition genetically.918

Unlike in Charcot–Marie–Tooth syndrome, the motor nerve conduction is normal, and the sensory nerve conduction is abnormal, especially in the lower extremities. Neuroophthalmologic manifestations include mild-to-severe optic atrophy in up to 25% of patients. While visual acuity may be affected, patients are frequently asymptomatic. In one study, 131 64% had abnormal visual evoked potentials. Using quantitative eye movement recordings, Moschner et al591 found frequent saccadic intrusions (especially square wave jerks and ocular flutter), low vestibuloocular reflex (VOR) gain, a prolonged low-frequency VOR phase in association with preserved pursuit, and optokinetic nystagmus (OKN) and VOR suppression with fixation. A Freidreich ataxia DNA test is now available to confirm the clinical diagnosis by identification of excessive trinucleotide repeats. Other than physiotherapy, no effective treatment is currently available.

Hereditary Polyneuropathies

The Charcot–Marie–Tooth diseases, also known as hereditary motor and sensory neuropathies, are a heterogenous group of disorders affecting primarily the peripheral nerves.918 Most are autosomal dominant disorder, but some are autosomal recessive. The autosomal dominant CMT1 presents in the first decade of life with a slowly progressive motor neuropathy affecting the lower more than the upper extremities. Affected children show distal wasting of the legs, impaired sensation, and reduced or absent reflexes, and foot drop or foot deformity (pes cavus). Optic atrophy rarely complicates the syndrome and is typically detected during the teenage years. The associated occurrence of Leber hereditary optic neuropathy in patients with Charcot–Marie–Tooth disease has been reported.552

CMT1 accounts for half of cases of Charcot–Marie–Tooth disease while CMT2 accounts for another 30–40%. CMT1A is usually caused by duplications or mutations in 17p11.2- 2.12 (PMP-22).918 Another autosomal form of Charcot– Marie–Tooth disease, CMT2A, is caused by mutations in the mitofusin 2 gene, which encodes a mitochondrial GTPase mitofusin protein, have recently been reported to cause both Charcot–Marie–Tooth disease and hereditary motor and sensory neuropathy VI.157,897 It is interesting that the mitofuscin