No content yeTACH, and map its locus to chromosome 10q22.3–10q23.31. This leukodystrophy presents around the same ages as the typical forms of metachromatic leukodystrophy and CACH (18 to 24 months and 12 months to 5 years of age, respectively) [
1]. The clinical features are somewhat similar to other forms of leukodystrophies presenting in early childhood, with progressive motor deterioration, spasticity, and other upper motor neuron signs. The more typical clinical characteristics of these cases are the presence of prominent ataxia and of an important postural and action tremor. To underline this clinical observation, we chose to call it TACH. We believe that this disease is better characterized as a leukodystrophy than an ataxia because of the universal white matter abnormalities on MRI studies (
Fig. 3) and because the clinical presentation is more complex, involving several other neurological systems. Its clinical presentation resembles CACH in several ways, with ataxia being an important clinical finding [
1]; however, MRI features are distinct from this disorder [
24]. The MRI findings of TACH are more consistent with the group of disorders characterized by hypomyelination, including those caused by GJA12/GJC2mutations or Pelizaeus-Merzbacher-like disease [
11], HCC, or hypomyelination with congenital cataracts [
25], and 4H or hypomyelination with hypodontia and hypogonadotropic hypogonadism, among others. Pelizaeus-Merzbacher-like disease was ruled out by sequencing the GJA12 gene. HCC was eliminated as a possible diagnosis in our cases because of inconsistent clinical features and different loci. The fact that the oldest case is treated for hypogonadotropic hypogonadism and that two participants are known for hypodontia raised the possibility that these patients may have a variant of 4H syndrome: hypomyelination, hypogonadotropic hypogonadism, and hypodontia [
26-
28]. The 4H syndrome was first described in 2005 [
29] in four unrelated girls with progressive ataxia, hypomyelination, and delayed dentition. Since the first description, a few more patients have been reported [
27-
30]. It is thought to be inherited in an autosomal recessive fashion, but the chromosomal locus is still unknown. Though there appears to be some clinical overlap between 4H and TACH, none of our cases have the full set of features. Only two out seven have missing teeth, and a single patient has hypogonadotropic hypogonadism. The two sural nerve biopsies on cases 6 and 7 were interpreted as normal. The nerve biopsy of case 7 was studied by electron microscopy and no abnormality supportive of a 4H diagnosis was uncovered. Nerve biopsies of patients with the 4H syndrome were reported to demonstrate clefts lined with granular debris, expanded abaxonal space, outpocketing with vacuolar disruption, and loss of normal myelin periodicity [
27]. The identification of the 4H locus or the gene for TACH will establish if the two disorders are allelic. To identify the mutated gene responsible for TACH, further genomic analyses will be required to further fine map the candidate region by recruiting additional families from Quebec and other countries. The identification of the TACH gene will contribute to our understanding of the mechanisms leading to inherited white matter diseases. It will also allow clinicians to offer definite diagnoses for one form of the growing number of leukodystrophies and genetic counseling to their families. t