RESUMEN
La trombocitopenia como motivo de consulta, requiere la búsqueda intencionada de orientar manifestaciones extrahematológicas. La megacariogénesis pasa por distintas etapas dependientes de la interacción de varios genes, entre ellos el MYH9, cuya expresión permite una adecuada formación y migración de las proplaquetas al ser liberadas al torrente sanguíneo, al mismo tiempo, existen estructuras con fisiología similar a nivel de citoesqueleto (podocitos, cilios cocleares, etc.) que podrían vincular a datos de pérdida de audición, enfermedad renal, cataratas y elevación de enzimas hepáticas conllevando a una enfermedad relacionada al gen MYH9. Se presenta el caso de un adolescente, de sexo masculino, con trombocitopenia recurrente, con el antecedente de padre con coagulopatía inespecífica, pérdida de audición, falla renal crónica, quien falleció a los 34 años por hemorragia intraparenquimatosa y edema cerebral severo, en quien se identifica una variante patogénica en heterocigosis en el gen MYH9, poniendo en relevancia la expresividad variable y efectos pleiotrópicos de este gen.
Thrombocytopenia as a reason for consultation requires an intense search to guide extrahematological manifestations. Megakaryogenesis goes through different stages depending on the interaction of several genes, including MYH9, whose expression allows proper formation and migration of proplatelets when released into the bloodstream, at the same time, there are structures with similar physiology at the cytoskeleton level (podocytes, cochlear cilia, etc.) that could be linked to data on hearing loss, kidney disease, cataracts and elevated liver enzymes leading to a disease related to the MYH9 gene. We present the case of an adolescent, male, with recurrent thrombocytopenia, with a history of a father with nonspecific coagulopathy, hearing loss, chronic kidney failure, who died at the age of 34 due to intraparenchymal hemorrhage and severe cerebral edema, in whom identifies a heterozygous pathogenic variant in the MYH9 gene, highlighting the variable expressivity and pleiotropic effects of this gene.
Asunto(s)
TrombocitopeniaRESUMEN
MYH9 disease is a rare genetic disorder in which there is a mutation in the gene for the non-muscle myosin heavy chain IIA. It initially causes macrothrombocytopenia followed by other clinical manifestations. When the patient reaches adulthood, he can develop chronic kidney failure. Thus, the risk of suffering a hemorrhage, difficulty in repairing and, infections increases in individuals with this disease. In addition, the use of drugs in these patients should be carefully evaluated. An adult patient sought dental care with a complaint associated with a tooth with advanced dental caries. He had severe thrombocytopenia (7000 platelets/mm3 ), hearing loss, and chronic kidney failure. The diagnosis of MYH9 disease was confirmed through genotyping. After clinical examination, extraction was planned. Local and systemic procedures were used to prevent hemorrhage, especially postoperatively. Although the patient had an infection at the surgical wound site and no episode of postoperative bleeding, the repair process occurred normally. The purpose of this article is to report the surgical management of a patient with MYH9 disease.
Asunto(s)
Caries Dental , Pérdida Auditiva Sensorineural , Fallo Renal Crónico , Trombocitopenia , Adulto , Masculino , Humanos , Cadenas Pesadas de Miosina/genética , Proteínas Motoras Moleculares/genética , Pérdida Auditiva Sensorineural/genética , Pérdida Auditiva Sensorineural/cirugía , Pérdida Auditiva Sensorineural/complicaciones , Trombocitopenia/complicaciones , Trombocitopenia/genética , Mutación , Fallo Renal Crónico/complicacionesRESUMEN
La enfermedad relacionada con MYH9, es un conjunto de síntomas que se expresan por la mutación de la cadena pesada de la miosina no muscular tipo IIA, la cual se expresa ampliamente en las células del cuerpo humano; dicho síndrome es una causa sindrómica de hipoacusia neurosensorial, que cada día ha aumentado su incidencia; y debido a lo anterior y además teniendo en cuenta que este tipo de pérdida auditiva es progresivo y severo, tiene una gran afección sobre la calidad de vida de los pacientes que presentan esta enfermedad, por lo tanto es importante conocer las manifestaciones clínicas relacionadas, la fisiopatología, y el tratamiento de elección en estos casos, con el fin de mejorar la calidad de vida de los pacientes.
MYH9 related disease, is a set of symptoms due to the mutation of the heavy chain of non-muscular myosin type IIA, which is widely expressed in the cells of the human body. It is a syndromic cause of sensorineural hearing loss, which has been increasing its incidence; and taking into account that this type of hearing loss is progressive and severe, its impact on the quality of life of patients is highly important. Therefore it is necessary to know the clinical manifestations related to pathophysiology, and the treatment of choice in these cases, in order to improve the quality of life of patients.
Asunto(s)
Humanos , Pérdida Auditiva Sensorineural , Síndrome , Trastornos de la AudiciónRESUMEN
We studied a family presenting 10 individuals affected by autosomal dominant deafness in all frequencies and three individuals affected by high frequency hearing loss. Genomic scanning using the 50k Affymetrix microarray technology yielded a Lod Score of 2.1 in chromosome 14 and a Lod Score of 1.9 in chromosome 22. Mapping refinement using microsatellites placed the chromosome 14 candidate region between markers D14S288 and D14S276 (8.85 cM) and the chromosome 22 near marker D22S283. Exome sequencing identified two candidate variants to explain hearing loss in chromosome 14 [PTGDR - c.G894A:p.R298R and PTGER2 - c.T247G:p.C83G], and one in chromosome 22 [MYH9, c.G2114A:p.R705H]. Pedigree segregation analysis allowed exclusion of the PTGDR and PTGER2 variants as the cause of deafness. However, the MYH9 variant segregated with the phenotype in all affected members, except the three individuals with different phenotype. This gene has been previously described as mutated in autosomal dominant hereditary hearing loss and corresponds to DFNA17. The mutation identified in our study is the same described in the prior report. Thus, although linkage studies suggested a candidate gene in chromosome 14, we concluded that the mutation in chromosome 22 better explains the hearing loss phenotype in the Brazilian family.