Agnieszka Madej-Pilarczyk

Polish Academy of Sciences, Warszawa, Masovian Voivodeship, Poland

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Publications (27)36.95 Total impact

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    ABSTRACT: Background: Emery-Dreifuss muscular dystrophy (EDMD) is a genetic condition associated with cardiac arrhythmias. The patients typically develop early, asymptomatic bradyarrhythmias, which may lead to sudden death, preventable with a cardiac implantable electronic device (CIED). EDMD may be characterized by atrial electrical silence. Intra-operative electrophysiological evaluation of the myocardium helps ultimately determine the true nature of the disorder and select an appropriate CIED. Aim: Analyze permanent electrotherapy procedures in EDMD patients: atrial pacing limitations which stem from electrophysiological properties of myocardium and long-term follow-up of implanted devices. Methods: A total of 21 EDMD patients (mean age 29 ± 9 yo.) with a CIED implanted (1976 - 2014) due to bradyarrhythmia were included in the study. The implantation procedures and factors determining the CIED type selection were analyzed. Results: CIEDs were implanted in 5 women and 16 men with EDMD types 1 and 2 (mean follow-up: 11 ± 8 years). Intra-operatively assessed atrial electrophysiology resulted in changing the planned CIED type during the procedure in 3 men with EDMD type 1. Eventually, we implanted: 8 DDD, 1 VDD, 11 VVI, and 1 CD-DR device, with 4 patients's devices switched later from DDD to VVI mode in response to electrophysiological changes in the atria. Conclusions: Intra-operative assessment of atrial electrophysiological properties resulted in changing the planned DDD mode for VVI in 19% of patients with EDMD type 1. Progression of the underlying disease over a 39-year follow-up resulted in a later change of the initially selected pacing mode from DDD to VVI in 40% of cases.
    No preview · Article · Nov 2015 · Kardiologia polska

  • No preview · Article · Oct 2015 · Kardiologia polska
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    ABSTRACT: Tissue inhibitors of matrix metalloproteinases (TIMPs) are known to be involved in cardiovascular diseases. Hitherto, they have not been examined in dilated cardiomyopathy (DCM) in course of Emery-Dreifuss muscular dystrophy (EDMD). The aim of this study was to define TIMPs in serum as they might help in defining cardiac dysfunction at early cardiological stages of this disease and detect preclinical stages of cardiomyopathy. Twenty five EDMD patients connected with lamin A/C (AD-EDMD) or emerin (X-EDMD) deficiency and 20 healthy age-matched controls were examined. The serum levels of the tissue inhibitors TIMP-1, -2, -3 were quantified using the ELISA sandwich immunoassay procedure with appropriate antibodies. Serum levels of TIMP-1 were normal in autosomal AD-EDMD, or increased in the majority of X-linked EDMD. The level of TIMP-2 was decreased in 25%/21% of AD-EDMD/X-EDMD cases. TIMP-3 serum level was significantly reduced in all the examined patients. Receiver operating curves (ROC) indicated that in terms of sensitivity and specificity characteristics the performance of TIMP-3, (less that of TIMP-2), makes them the best markers of cardiac involvement among the examined TIMPs. Evidence is provided that the levels of TIMP-3, in some cases also TIMP-2, are decreased in Emery-Dreifuss muscular dystrophy. The decrease might be associated with an adverse effect on MMPs and remodeling of the myocardial matrix. The specific decrease of TIMP-3 indicates that this biomarker might help in early detection of cardiac involvement in EDMD. Up-regulation of TIMP-1 in the majority of patient with X-EDMD indicates on increased ECM turnover, early onset of tissue remodeling and may contribute to arrhythmia, frequently occurring in this form of the disease.
    No preview · Article · Jan 2015 · Kardiologia polska
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    ABSTRACT: In recent years numerous mutations in the LMNA gene encoding lamin A/C were shown to segregate with a wide spectrum of phenotypes. A recurrent p.R377H mutation in the LMNA gene was reported in patients with Emery-Dreifuss dystrophy (EDMD2) with various ethnic backgrounds. We present a patient with EDMD2 caused by a p.R377H mutation, associated with mild peripheral polyneuropathy. The analysis of peripheral myelin protein 22 (PMP22), ganglioside-induced differentiation-associated protein 1 (GDAP1), gap junction β-1 protein (GJB1), and myelin protein zero (MPZ) genes did not reveal mutations; however, we identified a new sequence intronic variant in the mitofusin 2 (MFN2) gene of unknown pathogenic significance. A complex phenotype in the presented patient might depend either on single mutation in the LMNA gene or on bigenic defect; therefore, a wide genetic investigation is needed to elucidate the molecular background of EDMD2/polyneuropathy in this case.
    No preview · Article · Jan 2015 · Folia Neuropathologica
  • Agnieszka Madej-Pilarczyk
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    ABSTRACT: Objectives: Emery-Dreifuss muscular dystrophy (EDMD) is a very rare genetic disorder affecting skeletal and heart muscles. The aim of this study was to identify factors which might influence the ability to work in EDMD patients in Poland. Material and methods: The study included 24 patients suffering from either of the two EDMD forms: 17 with emerinopathy (EDMD1; EDMD caused by mutations in the emerin gene) and 7 with laminopathy (EDMD2; EDMD caused by the lamin A/C gene mutations). After clinical evaluation of EDMD course, study participants were questioned about their education, current and former employment, and disability certificates and pensions. Results: 54% of the study participants were employed, and 90% of them had job position corresponding to their education. Undertaking work did not correlate with the level of physical performance or disease complication, but it revealed statistically significant correlation with a higher level of education (p = 0.015). Only 23% of professionally active patients were employed in a sheltered workplace. Disability certificate was granted to all EDMD2 and to 90% of EDMD1 patients. All EDMD2 and 50% of EDMD1 patients received a disability pension, which reflects more severe course of EDMD2. Conclusions: Higher level of education increased the chance of employment, even if significant disability was present. Therefore, I hypothesize that advice on education and job counseling should be applied as early as possible after the diagnosis of EDMD.
    No preview · Article · Apr 2014 · International Journal of Occupational Medicine and Environmental Health

  • No preview · Article · Mar 2014 · International journal of cardiology
  • Anna Fidzianska · Maria Jędrzejowska · Agnieszka Madej-Pilarczyk · Jacek Bojakowski
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    ABSTRACT: Introduction: During human myogenesis and synaptogenesis, the first contact between multiaxonal nerve terminals and the primary myotube occurs at an early stage of gestation, then monoaxonal nerve terminals form and postsynaptic clusters of acetylcholine-receptor are modified and redistributed to the site of muscle-nerve contact. The aim of this study is to present the ultrastructural features of muscle and motor-junction immaturity severe enough to lead to death in the first months of life. Material and methods: Ultrastructural-level analysis was carried out on the quadriceps femoris muscle of an infant born at full term with severe respiratory distress but with normal SMN1 and IGHMBP2 genes. Results: Arrested muscle maturation was manifested in the presence of primary and mature myotubes, prepatterned acetylcholine-receptor clusters devoid of terminal axons, lack of synapses and multiaxonal unmyelinated intramuscular nerves. Conclusion: The "naked" prepatterned clusters observed on the surface of myotubes normally never observed in neonates might be a sign of a new genetic defect in innervation.
    No preview · Article · Dec 2013
  • Anna Fidzianska · Agnieszka Madej-Pilarczyk · Irena Hausmanowa-Petrusewicz
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    ABSTRACT: Congenital fiber type disproportion with delayed fiber type maturation and the appearance of cap structures were analyzed in a child with p.Arg168Gly mutation in TPM3 gene. Very narrow myotube-like Type 1 fibers with single nuclei decorated by cap structures seem to be a result of a failure in fusion process and mature fiber formation. Repeated mutations in exon 5 of TPM3 gene giving cap structures may be a different consequence of the loss of specific isoform normally operating in the fusion process and sarcomer formation.
    No preview · Article · Aug 2013 · Clinical neuropathology
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    Full-text · Dataset · Jun 2013
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    Mohammad Al-Haggar · Agnieszka Madej-Pilarczyk · Amany Shams · Monika Puzianowska-Kuznicka

    Full-text · Dataset · Jun 2013

  • No preview · Article · Jun 2013 · Journal of clinical pathology
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    ABSTRACT: Lamins (LMNA) are the main proteins of the nuclear lamina considered to be the ancestors of all intermediate filament proteins. They form complex protein assemblies with integral proteins of the inner nuclear membrane, transcriptional regulators, histones and chromatin modifiers. During recent years, interest in lamins has greatly increased due to the identification of many distinct heritable human disorders associated with lamin mutations. These disorders, collectively termed laminopathies, range from muscular dystrophies to premature aging. They may affect muscle, fat, bone, nerve and skin tissues. The workshop was addressed to understand lamin organization and its roles in nuclear processes, mutations in lamins affecting cell and tissues functions, the biology of the nucleus and laminopathic disease mechanisms, all aspects important for designing future therapies.
    Full-text · Article · May 2013 · Acta myologica: myopathies and cardiomyopathies: official journal of the Mediterranean Society of Myology / edited by the Gaetano Conte Academy for the study of striated muscle diseases
  • Anna Fidzianska · Agnieszka Madej-Pilarczyk · Ewa Walczak · Marek Kuch
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    ABSTRACT: Background: Danon disease is caused by a primary deficiency of lysosome-associated membrane protein-2 (LAMP-2). Materials and methods: Our study describes a 19-year-old man with isolated hypertrophic cardiomyopathy, in whom we performed DNA analysis and compared results of microscopic analysis of skeletal and cardiac muscles. Results: Sequencing of the LAMP-2 gene revealed a novel point mutation c.137G > A in exon 2, leading to premature stop codon. Ultrastructural analysis of cardiac and skeletal muscles revealed the presence of unusual autophagic vacuoles in both. Although some vacuoles in skeletal muscle reacted strongly with dystrophin, β-sarcoglycan, and laminin, those in cardiomyocytes showed no immunoreactivity. Conclusion: Our immunohistochemical and ultrastructural findings reinforce the claim that in Danon disease the pathomechanism of chaperone-mediated autophagy in cardiomyocytes differs from that in skeletal muscle.
    No preview · Article · Mar 2013 · Neuropediatrics
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    ABSTRACT: Spinal muscular atrophy with respiratory distress type 1 (SMARD1) is a very rare autosomal recessive form of spinal muscular atrophy manifested in low birth weight, diaphragmatic palsy and distal muscular atrophy. Caused by a mutation in the IGHMBP2 gene, the disease is addressed here by reference to five Polish patients in which SMARD1 has been confirmed genetically. All presented a severe form of the disease and had evident symptoms during the second month of life; with four displaying weak cries, feeding difficulties and hypotonia from birth. Two were afflicted by severe dysfunction of the autonomic nervous system. Ultrastructural analysis of a muscle biopsy revealed progressive degeneration within the nuclei of the muscle cells and Schwann cells. Neuromuscular junctions were also defective. It proved possible to identify in our patients 6 novel IGHMBP2 mutations: three missense (c.595G>C, c.1682T>C and c.1794C>A), two nonsense (c.94C>T and c.1336C>T) and one in-frame deletion (c.1615_1623del). One nonsense mutation (c.429C>T) that had been described previously was also identified. Observation of our patients makes it clear that clinical picture is still the most important factor suggesting diagnosis of SMARD1, though further investigations concerning some of the symptoms are required. As the IGHMBP2 gene is characterized by significant heterogeneity, genetic counseling of affected families is rendered more complex. IGHMBP2 protein deficiency can lead to the degeneration of nuclei, in both muscle and Schwann cells.
    Full-text · Article · Jan 2013 · European journal of paediatric neurology: EJPN: official journal of the European Paediatric Neurology Society
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    Full-text · Article · Jan 2013 · Journal of Clinical Pathology
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    ABSTRACT: Mandibuloacral dysplasia (MAD) is a rare disease resulting from a mutation of LMNA gene encoding lamins A and C. The most common mutation associated with this disease is a homozygous arginine 527 replacement by histidine. Three female patients originating from two unrelated families from Northeast Egypt were examined. Their growth was retarded; they had microcephaly, widened cranial sutures, prominent eyes and cheeks, micrognathia, dental crowding, hypoplastic mandible, acro-osteolysis of distal phalanges, and joint contractures. In addition, they presented some progeroid features, such as pinched nose, premature loss of teeth, loss of hair, scleroderma-like skin atrophy, spine rigidity, and waddling gait. The clinical presentation of the disease varied between the patient originating from Family 1 and patients from Family 2, suggesting that unknown, possibly epigenetic factors, modify the course of the disease. The first symptoms of the disease appeared at the age of 2.5 (a girl from Family 1), 5, and 3 years (girls from Family 2). All patients had the same, novel homozygous c.1580G>T LMNA mutation, resulting in the replacement of arginine 527 by leucine. Computational predictions of such substitution effects suggested that it might alter protein stability and increase the tendency for protein aggregation, and as a result, might influence its interaction with other proteins. In addition, restriction fragment-length polymorphism analysis performed in 178 unrelated individuals showed that up to 1.12% of inhabitants of Northeast Egypt might be heterozygous carriers of this mutation, suggesting the presence of a founder effect in this area.
    Full-text · Article · May 2012 · European journal of human genetics: EJHG
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    ABSTRACT: As osteopontin (OPN) may be assumed to have diagnostic/prognostic value in heart diseases, it is worth assessing whether it is also involved in the pathogenesis and can be applied in the diagnosis of the dilated cardiomyopathy (DCM) in Emery-Dreifuss muscular dystrophy (EDMD). Serum levels of osteopontin were quantified by means of sandwich immunoassay in 25 EDMD patients (10 laminopathies AD-EDMD and 15 emerinopathies--X-EDMD), eight carriers of X-EDMD, nine disease controls (patients with dystrophinopathy) and 20 age-matched healthy controls. The levels of circulating OPN were elevated in all AD-EDMD and X-linked EDMD patients, as well as in X-EDMD carriers and patients suffering progressive muscular dystrophy. There was no correlation between the osteopontin level and different cardiac parameters, including left-ventricular end-diastolic diameter, left atrial diameter, the left ventricular ejection fraction and the CK-MB level. There was a slight negative correlation with the ages of the patients. The presented results indicate that assessments of circulating OPN levels may help to identify EDMD patients at risk of dilated cardiomyopathy and might be therefore included among the set of biomarkers referred to with a view to appropriate early cardiologic diagnosis and therapy being commenced with in time.
    No preview · Article · Dec 2011 · Scandinavian journal of clinical and laboratory investigation
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    ABSTRACT: Tenascin-C (TN-C), an extracellular matrix glycoprotein, is of diagnostic and prognostic value in different heart diseases. One such dilated cardiomyopathy (DCM) with conduction disturbances is one of the most serious manifestations in Emery-Dreifuss muscular dystrophy (EDMD). Herein we therefore detail work to evaluate the potential significance of circulating TN-C in patients with EDMD, speculating that it may define the cardiac dysfunction, especially in patients who may be cardiac asymptomatic, but still be at risk of sudden death. Serum levels of TN-C were quantified by sandwich immunoassay ELISA in 25 EDMD patients (10 with laminopathy-AD-EDMD and 15 with emerinopathy-X-EDMD), 8 X-EDMD carriers, 9 disease controls (patients with dystrophinopathy), and 15 age-matched healthy controls. Fourteen of the EDMD patients had repeated TN-C examinations after 3 to 7 years. The levels of circulating TN-C were elevated in AD-EDMD and X-EDMD patients, as well as in some X-EDMD carriers, and patients with dystrophinopathy. The correlation between the TN-C level and left end-systolic ventricle diameter (LVDD) was significant in X-EDMD, while those with left atrium diameter (LAD) and the ejection fraction (EF) were not. In "follow-up" studies TN-C levels were not found to change over time in AD-EDMD, while rising in X-EDMD. The presented results indicate that assessments of circulating TN-C levels may help to identify EDMD patients at risk of dilated cardiomyopathy. TN-C might therefore be considered a candidate for a new biomarker, useful in detecting of cardiomyopathy and in further monitoring of the DCM therapy in patients with EDMD.
    No preview · Article · Aug 2011 · Clinica chimica acta; international journal of clinical chemistry
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    ABSTRACT: Familial partial lipodystrophy (FPLD) belongs to the family of laminopathies - disorders associated with mutation in the lamin A/C gene (LMNA). FPLD is characterized by loss of subcutaneous adipose tissue from the limbs, trunk and buttocks, with its concomitant accumulation on the face, neck and intra-abdominal region, and by metabolic disorders. We present the first Polish family with FPLD confirmed genetically. A 34-year-old woman admitted with myalgia and cushingoid appearance was found to have a round face with double chin, neck bump, and loss of fat on extremities. Diagnostic tests revealed impaired glucose tolerance and increased levels of liver enzymes, and ultrasonography revealed hepatic steatosis. Her 9-year-old daughter presented a similar phenotype, but no fat loss. A genetic test revealed the presence of a heterozygous LMNA gene mutation: c.1445G>A, consistent with the "hot spot" for FPLD. Treatment with metformin to improve insulin resistance and address the diabetes proved successful.
    No preview · Article · Dec 2010 · Neurologia i neurochirurgia polska
  • A Fidzianska · I Niebrój-Dobosz · A Madej-Pilarczyk · N T Duong · M Wehnert
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    ABSTRACT: The study demonstrates a 12-year-old patient with progressive proximal muscle weakness, joint contractures, rigidity of the neck, and absence of emerin and lamin A in the muscle nuclei, which is caused by intronic mutation IVS3-27del18 (c.266-27del18) in the emerin gene. The most surprising finding was the appearance of IBM-like inclusions in euchromatin, as well as aberrant nuclei. It may be speculated that altered expression of the emerin-lamin complex and modification of the nuclear matrix leads to formation of tubulofilamentous structures in the presented case.
    No preview · Article · Mar 2010 · Clinical neuropathology

Publication Stats

68 Citations
36.95 Total Impact Points


  • 2008-2015
    • Polish Academy of Sciences
      Warszawa, Masovian Voivodeship, Poland
  • 2014
    • Nofer Institute of Occupational Medicine
      Łódź, Łódź Voivodeship, Poland
  • 2009-2014
    • Mossakowski Medical Research Centre Polish Academy of Sciences
      Ochotnica, Lesser Poland Voivodeship, Poland