Abstract
Background MYH9-related disease (MYH9-RD) is a rare autosomal dominant genetic syndrome characterized by congenital thrombocytopenia associated with the risk of developing progressive nephropathy, sensorineural deafness, and presenile cataract. During the collection of a large case-series of patients with MYH9-RD we noticed several cases with unexplained elevation of liver enzymes. Our aim was to evaluate if the alteration of liver tests is a feature of the MYH9-RD and to define its clinical significance.Methods and FindingsData concerning liver tests, prospectively recorded in the Italian Registry for MYH9-RD, were collected and compared with those of three control populations: patients with autoimmune thrombocytopenia, patients with inherited thrombocytopenias other than MYH9-RD, and the participants to a large epidemiologic survey in an Italian geographic isolate. Thirty-eight of 75 evaluable MYH9-RD patients (50.7%) showed an elevation of ALT and/or AST, and 17 of 63 (27.0%) an increase of GGT. The increases ranged from 1.9±0.7 to 2.7±1.6 fold the upper normal limit. The prevalence of liver test alterations was significantly higher in MYH9-RD patients than in each of the control populations, with odds ratios ranging from 8.2 (95% CIs 2.2–44.8) to 24.7 (14.8–40.8). Clinical follow-up and more detailed liver studies of a subset of patients, including ultrasound liver scan, liver elastography and liver biopsy in one case, did not show any significant structural damage or evolution towards liver insufficiency.ConclusionsElevation of liver enzymes is a frequent and previously unrecognized feature of the MYH9-RD syndrome; however, this defect does not appear to have poor prognostic value.
Highlights
MYH9-related disease (MYH9-RD) is an autosomal dominant disorder characterized by congenital thrombocytopenia with giant platelets associated with the risk of developing progressive nephropathy during infancy or adult life, sensorineural deafness and presenile cataract [1,2]
MYH9-RD encompasses a series of autosomal dominant macrothrombocytopenias previously considered as distinct disorders, namely May-Hegglin anomaly (MHA; MIM#155100), Sebastian Syndrome (SBS; MIM#605249), Fechtner Syndrome (FTNS; MIM#153640), and Epstein Syndrome (EPTS; MIM#135650), all deriving from mutations in the MYH9 gene encoding for the heavy chain of nonmuscle myosinIIA (NMMHC-IIA) [1,2,3,4,5]
Aims of the present study were to carry out a systematic evaluation of the prevalence of alterations of liver enzymes in a large, wellcharacterized MYH9-RD population, to compare it with the prevalence observed in a large population survey performed in central eastern Sardinia [16] and in two populations of patients with thrombocytopenias not related to MYH9 mutations studied during the same period at the authors’ Centers, and to assess the evolution of the liver test alterations in terms of potential organ damage
Summary
MYH9-related disease (MYH9-RD) is an autosomal dominant disorder characterized by congenital thrombocytopenia with giant platelets associated with the risk of developing progressive nephropathy during infancy or adult life, sensorineural deafness and presenile cataract [1,2]. Sensorineural hearing loss, nephropathy and cataract are the only recognized clinical hallmarks of the MYH9-RD syndrome, previous studies have reported altered liver function tests in single cases or small case series of patients with MYH9-RD [13,14,15]. MYH9-related disease (MYH9-RD) is a rare autosomal dominant genetic syndrome characterized by congenital thrombocytopenia associated with the risk of developing progressive nephropathy, sensorineural deafness, and presenile cataract. During the collection of a large case-series of patients with MYH9-RD we noticed several cases with unexplained elevation of liver enzymes. Our aim was to evaluate if the alteration of liver tests is a feature of the MYH9-RD and to define its clinical significance
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
