RESUMEN
BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT), also known as Rendu-Osler-Weber syndrome, is a rare disorder characterized by recurrent epistaxis, telangiectasias and systemic arteriovenous malformations (AVMs). HHT is associated with mutations in genes encoding for proteins involved in endothelial homeostasis such as ENG (endoglin) and ACVRL1 (activin receptor-like kinase-1). CASE PRESENTATION: Here we describe a 22-year-old male presenting with a transient episode of slurred speech and left arm paresis. Brain MRI displayed polymicrogyria. A right-to-left shunt in absence of an atrial septum defect was noted. Chest CT revealed multiple pulmonary AVMs, likely causing paradoxical embolism manifesting as a transient ischemic attack. The heterozygous ENG variant, c.3G > A (p.Met1lle), was detected in the patient. This variant was also found in patient's mother and in his younger brother who displayed cortical dysplasia type 2. CONCLUSIONS: The detection of cortical development malformations in multiple subjects from the same pedigree may expand the phenotypic features of ENG-related HHT patients. We suggest considering HHT in young patients presenting with acute cerebral ischemic events of unknown origin.
Asunto(s)
Endoglina/genética , Malformaciones del Desarrollo Cortical/genética , Telangiectasia Hemorrágica Hereditaria/diagnóstico , Receptores de Activinas Tipo II/genética , Fístula Arteriovenosa/diagnóstico , Malformaciones Arteriovenosas/genética , Heterocigoto , Humanos , Masculino , Mutación , Arteria Pulmonar/anomalías , Venas Pulmonares/anomalías , Telangiectasia Hemorrágica Hereditaria/genética , Tomografía Computarizada por Rayos X , Adulto JovenRESUMEN
We report a 26-year-old woman admitted to our hospital for generalized tonic seizure. Laboratory investigations revealed severe hyponatremia possibly triggered by vomiting and diarrhea. 24 hours after correction of hyponatremia she developed diffuse myalgias and marked hyperCKemia. Syndrome of inappropriate antidiuresis (SIAD) was suspected as cause of hyponatremia. Abnormal vaginal bleeding prompts gynecological evaluation and a small-cell carcinoma of uterine cervix was detected.
Asunto(s)
Hiponatremia/diagnóstico , Síndrome de Secreción Inadecuada de ADH/diagnóstico , Síndromes Paraneoplásicos/diagnóstico , Rabdomiólisis/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico , Adulto , Diagnóstico Diferencial , Femenino , Humanos , Hiponatremia/terapia , Síndrome de Secreción Inadecuada de ADH/terapia , Rabdomiólisis/terapia , Neoplasias del Cuello Uterino/terapiaRESUMEN
Some missense mutations and small deletions in the NOTCH3 gene, not involving cysteine residues, have been described in patients considered to be affected by paucisymptomatic CADASIL. However, the significance of such molecular variants is still unclear. We describe a 49-year-old woman with a CADASIL-like phenotype, carrying a novel cysteine-sparing mutation in exon 29 of the NOTCH3 gene, and discuss the possible pathogenetic role of this molecular variant. Even though atypical clinical and MRI findings make a diagnosis of CADASIL unlikely in this patient, our report nevertheless underlines the intriguing genotype-phenotype relationship in NOTCH3 mutations and the importance of functional investigation to ascertain the role of new NOTCH3 mutations in CADASIL pathogenesis.