Clinical and mutational spectrum of Colombian patients with Pelizaeus Merzbacher Disease.
| Autor: | Velasco Parra HM; Maestria en Genética Humana, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Colombia.; Hospital Militar Central, Bogotá, Colombia.; Instituto de Ortopedia Infantil Roosevelt, Bogotá, Colombia., Maradei Anaya SJ; Maestria en Genética Humana, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Colombia., Acosta Guio JC; Maestria en Genética Humana, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Colombia.; Instituto de Ortopedia Infantil Roosevelt, Bogotá, Colombia., Arteaga Diaz CE; Maestria en Genética Humana, Facultad de Medicina, Universidad Nacional de Colombia, Bogotá, Colombia., Prieto Rivera JC; Genetica Medica, Facultad de Medicina, Pontificia Universidad Javeriana. Bogotá, Colombia.; Hospital La Victoria, Bogotá, Colombia. |
|---|---|
| Jazyk: | angličtina |
| Zdroj: | Colombia medica (Cali, Colombia) [Colomb Med (Cali)] 2018 Jun 30; Vol. 49 (2), pp. 182-187. Date of Electronic Publication: 2018 Jun 30. |
| DOI: | 10.25100/cm.v49i2.2522 |
| Abstrakt: | Case Presentation: Pelizaeus Merzbacher Disease (PMD) is an X-linked developmental defect of myelination that causes childhood chronic spastic encephalopathy. Its genetic etiology can be either a duplication (or other gene dosage alterations) or a punctual mutation at the PLP1 locus. Clinically, it presents with developmental delay, nystagmus and, spasticity, supported by neuroimaging in which the defect of myelination is evident. We present a series of seven Colombian patients diagnosed with this leucodystrophy, describing their genotypic and phenotypic characteristics and heterogeneity. Clinical Findings: All patients included were male, 6 months to 16 years of age. Mean age at onset of symptoms was 8 months. Mean age at diagnosis was 5 years 5 months, being classic PMD most frequently diagnosed, as compared to the connatal phenotype. All cases had a primary diagnosis of developmental delay on 100%, and in 28.7% of cases, early onset nystagmus was described. 85.7% of patients had spasticity, 71.4% cerebellar signs, 57.0% hypotonia, and 28.5% had an abnormal movement disorder. Only three patients were able to achieve gait, though altered. In the two patients who had a diagnosis of connatal PMD maturational ages in danger zones according to the WHO Abbreviated Scale of Psychosocial Development were documented. All cases had abnormalities in neuroimages. Molecular Analysis and Results: Molecular studies were used in the majority of the cases to confirm the diagnosis (85.7 %). For two cases molecular confirmation was not considered necessary given their affected male brothers had already been tested. PLP1 gene dosage alterations (duplications) were found in 28.5 % of the patients (two siblings), whereas three different single nucleotide variants were detected. Clinical Relevance: According to these findings, as authors we propose the diagnostic algorithm in Colombian population to begin on a high clinical suspicion, followed by paraclinical extension, moving on to the molecular confirmation by using approaches to simultaneously sequence the PLP1 gene in order to detect point mutations and in/dels and performing a copy number variation analysis for the detection of gene dosage alterations. Competing Interests: Conflict of interests The authors declare that they have no competing interests |
| Databáze: | MEDLINE |
| Externí odkaz: |
|