Dados do Trabalho

Título

Autosomal Dominant Hereditary Spastic Paraplegia with pure phenotype and early onset caused by variant in the KIF1A gene.

RESUMO

CASE PRESENTATION:
A 14-year-old male patient started walking on tiptoe at one and a half years of age. These symptoms evolved progressively. On current physical examination, he has grade IV strength in dorsiflexion of the feet and interosseous in the hands, patellar and achilleus hyperreflexia, bilateral Achilles clonus, bilateral Babinski sign and reduced vibratory sensitivity. Mild hyperreflexia in upper limbs. He also has low-amplitude, high-frequency postural and kinetic tremor. His parents are not consanguineous and there are no similar cases in the family. He performed investigation of sporadic and metabolic causes that showed no changes, as well as MRI of the skull and spinal cord. We opted for genetic investigation with a diagnosis of pure Hereditary Spastic Paraplegia (HSP), as an isolated case, through a panel of genes. In this, the probably pathogenic variant was found in the KIF1A gene c.1021A>G (p.Thr341Ala), in heterozygosity. This was also evaluated in their parents, who did not have the mutation. Thus, the diagnosis of SPG30, pure form, autosomal dominant (AD), with early onset, was concluded.
DISCUSSION:
Hereditary Spastic Paraparesis is a heterogeneous group of rare neurogenetic disorders caused by variants in more than 80 genes, with all forms of inheritance already described. They are divided into pure or complicated forms, according to the clinical presentation. SPG30, caused by variants in the KIF1A gene, which encodes a motor protein expressed exclusively in brain tissue and transports cargoes from the neuronal body to the periphery of neurites. In addition to the two forms of inheritance, AD conditions have already been described as pure in some families and as complicated in others, and also as a cause of polyneuropathy, sometimes making it difficult to confirm the pathogenicity of the variant. Few cases with this phenotype have been described in the Brazilian population.
FINAL COMMENTS:
A better understanding of the variants found in the Brazilian population and, consequently, which forms of HSP we find here, helps in the interpretation of molecular results and even in the creation of more directive gene panels, depending on the origin of the patient. In addition, better understanding the changes caused by mutations in the KIF1A gene further broadens the spectrum of diseases associated with it.

Palavras Chave

Hereditary spastic paraplegia; SPG30, KIF1A.