A novel LAMP2 mutation associated with severe cardiac hypertrophy and microvascular remodeling in a female with Danon disease: a case report and literature review

作者：Bottillo Irene^*; Giordano Carla; Cerbelli Bruna; D'Angelantonio Daniela; Lipari Martina; Polidori Taisia; Majore Silvia; Bertini Enrico; D'Amico Adele; Giannarelli Diana; De Bernardo Carmelilia; Masuelli Laura; Musumeci Francesco; Avella Andrea; Re Federica; Zachara Elisabetta; d'Amati Giulia; Grammatico Paola

来源：Cardiovascular Pathology, 2016, 25(5): 423-431.

DOI：10.1016/j.carpath.2016.07.005

• Danon disease
• LAMP2
• X-chromosome inactivation study (XCI)
• Cardiac hypertrophy
• Lysosomal vacuoles
• Microvascular remodeling
• Genotype-Phenotype correlations

Background: Danon disease (DD) is a rare disorder characterized by cardiomyopathy, intellectual disability, and proximal myopathy. It is caused by mutations in the LAMP2 gene on X chromosome. Female patients most often present with late-onset cardiomyopathy and slow disease progression, but early-onset cases with unfavorable prognosis have been reported.
Case report: We describe the clinical, pathological, and molecular features of a novel LAMP2 c.453delT mutation in a female patient with severe hypertrophic cardiomyopathy, Wolff Parkinson White (WPW) syndrome and rapid progression to heart failure, requiring heart transplant. Immunohistochemical analysis of LAMP2 in the explanted heart revealed a mosaic pattern of distribution, with discrete clusters of either stained or unstained cardiac myocytes, the latter being more frequent in the septum. These findings paralleled X chromosome inactivation within the myocardium. Interestingly, multiple foci ofmicroscarring were found on histology in the Left Ventricle (LV) free wall and septum, in a close spatial relationship with remodeling and severe stenosis of intramural coronary arterioles.
Conclusions: Our findings suggest that several features may contribute to the early and severe cardiac phenotype in female DD patients. The type of mutation may account for the early disease onset, while both the inhomogeneous distribution of LAMP2 loss and the presence of microvascular remodeling may be determinant in the rapid progression to heart failure.

• 出版日期2016-10