Approach to hereditary ataxia/spastic paraplegia in childhood

Spinocerebellar ataxias are characterized by disturbances of the body posture and coordination. They may result from one or any combination of dysfunction of the cerebellum and its associated systems, lesions in the spinal cord, or peripheral sensory loss. Other nervous system structures that are usually affected in spinocerebellar ataxia include the basal ganglia and brainstem nuclei.

According to the mode of inheritance and gene in which causative mutations occur or chromosomal locus, spinocerebellar ataxias can be subdivided into autosomal dominant, autosomal recessive, X-linked, and mitochondrial. The underlying genetic defect remains unknown in about 40 % of suspected genetically determined ataxia cases. Nevertheless, the high incidence of consanguineous marriages in North Africa, including Sudan, and the Arabian Peninsula is reflected on the high prevalence of autosomal recessive (AR) disorders, in contrast to the situation in North America and Europe. The current presentation outlines a diagnostic clinical and investigational algorithm for hereditary ataxia/spastic paraplegia in childhood. Utilizing this algorithm and the power of family-based genetic studies combined with emerging DNA technology, new syndromes and diseases were identified. Those with gene identification included:

1. A new form of childhood-onset, autosomal recessive spinocerebellar ataxia and epilepsy: (http://brain.oxfordjournals.org/cgi/content/full/130/7/1921) (http://www.ncbi.nlm.nih.gov/pubmed/24369382).

2. Spinocerebellar ataxia with axonal neuropathy (SCAN1; OMIM 607250; http://www.ncbi.nlm.nih.gov/books/NBK1105/).

3. Salih ataxia:

   (OMIM #615705, http://omim.org/entry/615705)

   (http://brain.oxfordjournals.org/content/133/8/2439.full.pdf+html)

   (http://www.ncbi.nlm.nih.gov/pubmed/23728897).

4. A new form of childhood-onset autosomal recessive hereditary spastic paraplegia (SPG56) caused by a novel gene (CYP2U1) mutations (OMOM # 615030).

   (http://omim.org/entry/615030)

   (http://www.cell.com/AJHG/abstract/S0002–9297%2812%2900579–4).

These advances of pediatric neurogenetics helped in refashioning the prognosis and differential diagnosis of these diseases. It also made possible presymptomatic, prenatal, and pre-implantation genetic diagnoses for affected families.

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