Familial childhood onset, slowly progressive myopathy plus cardiomyopathy expands the phenotype related to variants in the TTN gene.

This report describes a novel TTN -related phenotype in two brothers, both affected by a childhood onset, very slowly progressive myopathy with cores, associated with dilated cardiomyopathy only in their late disease stages. Clinical exome sequencing documented in both siblings the heterozygous c.2089A>T and c.19426+2T>A variants in TTN. The c.2089A>T, classified in ClinVar as possibly pathogenic, introduces a premature stop codon in exon 14, whereas the c.19426+2T>A affects TTN alternative splicing. The unfeasibility of segregation studies prevented us from establishing the inheritance mode of the muscle disease in this family, although the lack of any reported muscle or heart symptoms in both parents might support an autosomal recessive transmission. In this view, the occurrence of cardiomyopathy in both probands might be related to the c.2089A>T truncating variant in exon 14, and the childhood onset, slowly progressive myopathy to the c.19426+2T>A splicing variant, possibly allowing translation of an almost full length TTN protein.

Intensive Care Unit-Acquired Weakness after Liver Transplantation: Analysis of Seven Cases and a Literature Review.

Intensive Care Unit (ICU)-Acquired Weakness (ICU-AW) is a generalized muscle weakness that is clinically detected in critical patients and has no plausible etiology other than critical illness. ICU-AW is uncommon in patients undergoing orthotopic liver transplantation (OLT). Our report sheds light on the highest number of ICU-AW cases observed in a single center on OLT patients with early allograft dysfunction. Out of 282 patients who underwent OLT from January 2015 to June 2023, 7 (2.5%) developed generalized muscle weakness in the ICU and underwent neurophysiological investigations. The neurologic examination showed preserved extraocular, flaccid quadriplegia with the absence of deep tendon reflexes in all patients. Neurophysiological studies, including electromyography and nerve conduction studies, showed abnormalities with fibrillation potentials and the rapid recruitment of small polyphasic motor units in the examined muscles, as well as a reduced amplitude of the compound muscle action potential and sensory nerve action potential, with an absence of demyelinating features. Pre-transplant clinical status was critical in all patients. During ICU stay, early allograft dysfunction, acute kidney injury, prolonged mechanical ventilation, sepsis, hyperglycemia, and high blood transfusions were observed in all patients. Two patients were retransplanted. Five patients were alive at 90 days; two patients died. In non-cooperative OLT patients, neurophysiological investigations are essential for the diagnosis of ICU-AW. In this setting, the high number of red blood cell transfusions is a potential risk factor for ICU-AW.