Brain Advance Access originally published online on September 13, 2004
Brain 2004 127(10):2173-2182; doi:10.1093/brain/awh263
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Brain Vol. 127 No. 10 © Guarantors of Brain 2004; all rights reserved
Action myoclonus–renal failure syndrome: characterization of a unique cerebro-renal disorder
1 Neurogenetics Unit and 2 Epilepsy Service, Montreal Neurological Hospital and Institute, 3 Department of Human Genetics, 4 Department of Neurology and Neurosurgery, 5 Department of Pediatrics and 6 MRS Unit, McConnell Brain Imaging Center, McGill University, 7 Département de Génetique Médicale, Hôpital Sainte-Justine, Montreal, 8 Service de Neurologie, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Quebec, 9 British Columbia Neuropsychiatry Program, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada, 10 Epilepsy Research Centre, Department of Medicine, University of Melbourne, Austin Health, 11 Department of Pathology, Alfred Hospital, 12 Department of Anatomical Pathology, Royal Melbourne Hospital, 13 Department of Neurology, Royal Melbourne Hospital, Melbourne Victoria, Australia and 14 Parkinson's Disease and Other Movement Disorders Center, Mayo Clinic, Scottsdale, Arizona, USA, 15 Universität Göttingen, Paracelsus-Elena-Klinik, Kassel, 16 Max Planck Institut für Psychiatrie and Institute of Human Genetics, National Research Center, Munich, Germany, 17 Instituto de Neurologia Pilar, Hospital N. S. Pilar, Curitiba, Brazil and 18 Serviço de Anatomia Patológica, Hospital de São João, Porto, Portugal
Correspondence to: Eva Andermann, MD, PhD, FCCMG, Neurogenetics Unit, Room 127, Montreal Neurological Hospital and Institute, 3801 University Street, Montreal, Quebec H3A 2B4, Canada E-mail: eva.andermann{at}mcgill.ca
Received February 10, 2004. Revised June 7, 2004. Accepted June 10, 2004.
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Action myoclonus–renal failure syndrome (AMRF) is a distinctive form of progressive myoclonus epilepsy associated with renal dysfunction. The syndrome was not recognized prior to the advent of dialysis and renal transplantation because of its rapidly fatal course if renal failure is untreated. The first and only description of AMRF was in four French Canadian patients in three families (Andermann et al., 1986
). We now describe 15 individuals with AMRF from five countries, including a follow-up of the four French Canadian patients, allowing a more complete characterization of this disease. Our 15 patients with AMRF belong to nine different families. Segregation analyses were compatible with autosomal recessive inheritance. In addition, our findings show that AMRF can present with either renal or neurological features. Tremor (onset 17–26 years, mean 19.8 years, median 19 years) and progressively disabling action myoclonus (onset 14–29 years, mean 21.7 years, median 21 years), with infrequent generalized seizures (onset 20–28 years, mean 22.7 years, median 22 years) and cerebellar features are characteristic. Proteinuria, detected between ages 9 and 30 years in all cases, progressed to renal failure in 12 out of 15 patients within 0–8 years after proteinuria detection. Brain autopsy in two patients revealed extraneuronal pigment accumulation. Renal biopsies showed collapsing glomerulopathy, a severe variant of focal glomerulosclerosis. This study extends the AMRF phenotype, and demonstrates a more extensive ethnic and geographic distribution of a syndrome originally believed to be confined to individuals of French Canadian ancestry. The independent progression of neurological and renal disorders in AMRF suggests a unitary molecular lesion with pleiotropic effects. Our results demonstrate that the renal lesion in AMRF is a recessive form of collapsing glomerulopathy. Genes identified for focal segmental glomerulosclerosis and involved with the function of the glomerular basement membrane and related proteins are thus good candidates. Treatment can improve quality of life and extend the lifespan of these patients. Dialysis and renal transplantation are effective for the renal but not the neurological features, which continue to progress even in the presence of normalized renal function; the latter can be managed with anti-myoclonic and anti-epileptic drugs.
Key Words: action myoclonus; renal failure; progressive myoclonus epilepsy; cerebro-renal disorder; autosomal recessive inheritance
Abbreviations: AMRF = action myoclonus–renal failure syndrome
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Introduction |
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The progressive myoclonus epilepsies are a clinically and aetiologically heterogeneous group of disorders. They are characterized by the association of action myoclonus, generalized tonic–clonic epileptic seizures, and progressive neurological deterioration with ataxia and often dementia (Berkovic et al., 1986
, 1993; Marseille Consensus Group, 1990).
Action myoclonus–renal failure syndrome (AMRF, OMIM 254900) is a rare form of progressive myoclonus epilepsy associated with severe renal dysfunction. The syndrome was not recognized prior to the advent of dialysis and renal transplantation because of its rapidly fatal course if renal failure is untreated. The first description of AMRF (Andermann et al., 1986) was in four French Canadian patients from three sibships who presented with tremor of the fingers and hands and proteinuria at 17–18 years of age. Severe progressive action myoclonus, dysarthria, ataxia, infrequent generalized seizures and renal failure ensued between 19 and 23 years of age. Intelligence remained normal in all four patients (Andermann et al., 1986). We had previously noted that a case published as ‘pigment variant of neuronal ceroid lipofuscinosis’ (Horoupian and Ross, 1977) had clinical and pathological features of AMRF. We are unaware of any other reports of this disorder (Andermann et al., 1986; Berkovic et al., 1986, 1993).
We now describe 15 individuals with AMRF from five countries, including a follow-up of the four French Canadian patients, allowing a more complete characterization of the clinico-pathological phenotype, genetics and natural history of this peculiar cerebro-renal disorder.
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Patients
We studied the clinical features of 15 patients from nine families of different ethnic origin (Table 1, Fig. 1). Eleven new patients with AMRF were ascertained for the study. The patients were recruited from the Montreal Neurological Hospital and Institute, Hôpital Sainte-Justine and the University of British Columbia Hospital, Canada; Mayo Clinic, Scottsdale, USA; Royal Melbourne Hospital, Australia; Max-Planck-Institut für Psychiatrie, Germany; and the Neurological Institute of Havana, Cuba. Additionally, a detailed follow-up was conducted on the four original French Canadian patients described in 1986. Informed consent was obtained from all families, in accordance with all local institutional review board guidelines.
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= male; 
= female; 
= deceased male; 
= deceased female; 
= miscarriage; 
= male stillbirth; == = consanguineous marriage; 
= dizygotic twins; 
= proband; 
= male with AMRF; • = female with AMRF.Genetics
A detailed genealogical history was obtained from each family. Family pedigrees, starting from the oldest generation provided and including extended family members, were constructed with the program Progeny 5.1.01 (Progeny Software). Family genealogy books provided by two French Canadian index patients helped establish a genealogical link between the two families.
Segregation analyses were carried out assuming complete, single and multiple incomplete ascertainment. The a priori method assuming complete truncate ascertainment was also employed (Stern, 1960; Thompson and Thompson, 1966; Andermann et al., 1976).
Data analysis
Relationships between variables were assessed via Pearson correlation, performed using SPSS version 11.0.1 for Macintosh (SPSS Inc.).
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Results |
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The clinical features are summarized in Table 1.
Neurological features
Bilateral fine tremor of fingers and hands was the first neurological symptom with age of onset from 17 to 26 years (mean 19.8 years; median 19 years). Present at rest, the tremor was considerably increased by fine motor activities such as writing. Progression of the disease brought about progressive worsening of the tremor with involvement of head, trunk and sometimes the tongue. In the late stages of the disease, the tremor was largely replaced by severe multifocal action myoclonus.
Onset of action myoclonus was from 14 to 29 years (mean 21.7 years; median 21 years). Conversation, concentration, anxiety and fatigue worsened the myoclonus. Speech, attempted and executed, induced bulbar myoclonus. Palatal myoclonus was not present. The myoclonus was reflex-sensitive to touch on distal extremities. Some patients exhibited occasional jerks in response to startle. Asynchronous jerks of variable severity of the arms and/or legs, facial and truncal myoclonus were also present at rest. Action myoclonus proved to be the most debilitating feature of the disease; treatment with multiple anti-epileptic and anti-myoclonic drugs including valproate, clonazepam, barbiturates and piracetam was partially effective. In the final stages, myoclonus rendered the patients bedridden or wheelchair-bound with lap, trunk and leg belts.
Convulsive seizures occurred in 11 out of 15 patients (73%); onset ranged from 20 to 28 years (mean 22.7 years, median 22 years). Diurnal or nocturnal in nature, the seizures started with a generalized clonic phase with preserved consciousness proceeding to unconsciousness with tonic–clonic features. Frequency of the seizures ranged from one to nine per annum initially. Control of major seizures was achieved with anti-epileptic drugs, despite ongoing active myoclonic jerks.
Ataxia and dysarthria were observed in all patients as the disease progressed. Although it is difficult to distinguish ataxia from action myoclonus, neurological evidence of cerebellar abnormalities, namely pendular reflexes, abnormal rebound, and nystagmus found in some patients, was further indicative of an underlying ataxic component.
Thirteen patients were of normal intelligence, and two were regarded as having slight cognitive impairment. It was striking that there was no evidence of the intellectual deterioration and dementia characteristic of that seen in most other forms of progressive myoclonus epilepsies such as Lafora disease and the adolescent and adult forms of neuronal ceroid lipofuscinosis (Kufs' disease). Two patients had significant depression.
No patient had clinical evidence of a peripheral neuropathy. The results of peripheral electrophysiology were available on six patients in four families, and only one of three affected siblings in a German family had evidence of a predominantly axonal neuropathy. The results in the other two siblings showed some abnormalities, but were difficult to interpret. Three other unrelated patients had normal findings.
The main EEG findings were generalized epileptiform abnormalities, often photosensitive, as well as diffuse slow wave disturbance of background activity. Background activity was normal in some patients. At times, single spike and slow wave discharges were recorded corresponding to the myoclonic jerks.
Neuroimaging with CT or MRI was obtained in 11 patients and was reported as normal in three, whereas eight had diffuse cerebral atrophy often associated with cerebellar atrophy.
Renal features
Proteinuria occurred in all cases and was detected between ages 9 and 30 years (mean 20.1 years, median 19 years). In some patients, proteinuria was detected during routine testing for pregnancy, minor surgery or military medical exam. Progression of renal impairment to renal failure requiring dialysis and/or transplantation occurred in 12 out of 15 patients within 0–8 years (mean 3.8 years, median 4.5 years) after proteinuria was recognized. Nine out of 15 patients had had a renal transplantation by the time of their last follow-up. These were performed between the ages of 13 and 31 years in seven patients where the information is known (Table 1). One patient (P08) died of complications of neurological involvement 10 years after neurological onset and 5 years after proteinuria was detected without significant further renal impairment; two living patients (P10 and P14) have not yet proceeded to renal failure, with follow-up of 15 and 14 years, respectively.
Relationship between neurological and renal features
In five patients, the first symptom was neurological (tremor and/or myoclonus), whereas in four, renal dysfunction was detected before the onset of tremor or myoclonus. In the remaining six patients, neurological and renal features were detected more or less simultaneously. There was no correlation between the ages of onset of proteinuria and tremor (Pearson R = 0.28; P = 0.31), nor between renal failure and myoclonus onset (Pearson R = –0.168; P = 0.60). Nine patients died at ages 25–35 years (mean 30.1, median 31 years), 7–23 (mean 12.4 years, median 11 years) years after onset of the first symptom. In three, death was related primarily to respiratory complications of the neurological syndrome; in four, it was due to renal failure or complications due to renal transplantation or dialysis.
Genetics
The 15 AMRF patients belonged to nine different families and originated from Canada, Germany, Cuba, Australia and the USA (Fig. 1, Table 1). Four families (families D, E, F and G) were of French Canadian descent and originated from rural areas of southern Québec. A common ancestral surname linked two families to immigrants from Ile de France and Normandie, adjacent provinces in 17th century France, suggesting a founder effect. The fifth Canadian family (family C, P03) was not French Canadian, but had possible French ancestors on both sides, and the family from the USA (family A, P01) had one ancestor with French origins. There were no known French Canadian or French ancestors in the other three families.
We determined that the mode of inheritance in these families was autosomal recessive, based on the absence of affected cases in previous generations, two or more affected siblings in four families, verified parental consanguinity in three families, and parental origins from the same rural areas in six families (families F and D). Table 2A shows the distribution of affected individuals in the nine sibships. Segregation analyses assuming complete, single and multiple incomplete ascertainment were compatible with autosomal recessive inheritance (Table 2B). The a priori method (Table 2C), comparing the number of affected observed and expected assuming complete truncate ascertainment, was also compatible with autosomal recessive inheritance [
2(4) = 1.671, P > 0.80].
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Pathology
Neuropathology
Post-mortem examination of the Australian patient (P02) was available and was compared with that of the previously published Canadian patient (P06) (Andermann et al., 1986
). The fixed brain of the Australian case weighed 1380 g. External examination was essentially normal and no abnormality was identified in serial coronal slices of the cerebral hemispheres and brainstem and sagittal slices of the cerebellum. Histological examination showed accumulation of irregularly shaped, refractile and autofluorescent granules of pigment, up to 10 µm in their greatest dimension. These were most prominent in laminae I and II of the cerebral cortex, in the globus pallidus and putamen, and in the layer of Bergmann astrocytes in the cerebellar cortex. The granules appeared both separate from and adjacent to glial cell nuclei, suggesting that at least some were within astrocytes. Pigment granules were not seen in the thalamus, brainstem nuclei, dentate nuclei of the cerebellum or spinal cord grey matter. The pigment granules showed golden brown autofluorescence in unstained de-paraffinized sections (Fig. 2A and B), stained black with Sudan black (Fig. 2C), dark blue–black with Luxol fast blue (Fig. 2D), golden brown with haematoxylin and eosin (Fig 2E and F), orange–brown with periodic acid–Schiff (PAS; Fig. 2G), and were negative for Perls' iron stain. Neurons in the cerebral cortex showed an accumulation of pigment consistent with lipofuscin that did not appear excessive. No significant loss of cerebral cortical neurons or Purkinje cells was seen.
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Electron microscopy, undertaken on cerebellar cortex, in the layer of Bergmann astrocytes, showed electron-dense deposits which appeared to be formed by concretion of globules
0.6 µm in diameter (Fig. 2H). A membrane was noted to surround the deposits incompletely, suggesting an intracellular location. Many of these deposits had both dense and paler areas. Within the denser areas, lamellae were often found (Fig. 2I), while in the paler areas there were often small trilaminar fragments.
Renal pathology
Renal biopsy specimens of two German (P13 and P15) and one Australian patient (P02) were available. All three patients had focal glomerulosclerosis, with features of collapsing glomerulopathy evident in two of these (P02 and P13) (Fig. 3). One of the two German patients (P13) showed patterns of both collapse and hyalinosis/sclerosis. The other German patient (P15) showed a pattern of segmental sclerosis/hyalinosis alone. Limited material was available for review from an original French Canadian patient (P07); there was evidence of focal glomerulosclerosis, but features of collapsing glomerulopathy were not seen.
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Discussion |
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AMRF is a distinctive form of progressive myoclonus epilepsy that can be diagnosed clinically and is inherited as an autosomal recessive trait (Table 2). From a neurological point of view, tremor as an early feature should raise a suspicion of the condition. Unlike most progressive myoclonus epilepsies, intellect is remarkably preserved in this disorder. This may relate to the fact that storage is not intraneuronal, as it is in many other forms of progressive myoclonus epilepsy (Berkovic et al., 1986
, 1993). Suspicion of this disorder should also be raised by the presence of proteinuria and progressive renal impairment in an adolescent or young adult with myoclonus epilepsy.
The clinical spectrum in this series demonstrates that AMRF can present with either renal or neurological features, typically at the end of the second decade, but with a range between 9 and 25 years. Tremor and progressively disabling multifocal action myoclonus with infrequent tonic–clonic seizures and cerebellar features are characteristic. The absence of dementia is striking. This perspective, from a study of 15 cases, confirms and extends the phenotype initially described in four French Canadian patients (Andermann et al., 1986). Clinical peripheral neuropathy was absent, but electrophysiological evidence of neuropathy was observed in one family; this may relate to uraemic neuropathy (Ahonen, 1981) rather than being a core feature of the neurological phenotype.
Superficially, in patients with advanced renal disease, one might confuse this syndrome with uraemic encephalopathy (Mahoney and Arieff, 1982; Lockwood, 1989). However, the clinical picture of AMRF is different, with a clear sensorium and lack of improvement in neurological features with dialysis or transplantation. Moreover, the facts that the neurological manifestations precede renal involvement in about one-third of the cases, and a specific form of storage material is present in the brain, clearly distinguish AMRF from uraemic encephalopathy.
The age of onset of this disorder (adolescent to young adult) may raise the question of Kufs' disease (Berkovic et al., 1988). AMRF differs clinically from Kufs' disease by the absence of dementia and by the associated renal involvement. The storage material observed in brain could lead to a pathological misdiagnosis of Kufs' disease. However, as previously pointed out, the storage in AMRF is extraneuronal, whereas in Kufs' disease there is prominent intraneuronal storage (Carpenter et al., 1977).
The brain histological and electron microscopic features of the Australian case described here were identical to those of the previously published Canadian patient (Andermann et al., 1986). The pigment accumulated in AMRF, which has yet to be characterized biochemically, is likely to be lipofuscin-like oxidized lipid or proteolipid based on its staining characteristics. It has different ultrastructural characteristics from those observed in Kufs' disease. The pigment is extraneuronal, in astrocytes or in the extracellular space, and there is no increase in intraneuronal lipofuscin. The contribution of chronic dialysis to a heightened state of lipid peroxidation may have a role in the pathogenesis of the pigment formation, as the use of vitamin E and other antioxidants in dialysis patients is a relatively recent practice. No such pigment has been observed so far in the renal biopsies.
The clinical tempo of this disorder varies somewhat within and between families. The first clinical symptoms can be renal or neurological. The progression of neurological and renal disorders appears to be separate. We interpret these findings to indicate that the unitary molecular lesion has pleiotropic effects, differentially affecting the two organ systems.
The initial description of this disorder was only in French Canadians, suggesting that it might be confined to this isolate. The current study demonstrates that this syndrome has a more extensive ethnic and geographic distribution, and we suspect that it is probably under-recognized. It is possible that cases with a predominantly renal presentation and later neurological disease are misdiagnosed as uraemic encephalopathy.
In progressive myoclonus epilepsies, there is presumably a unique physiological system involved, leading to the characteristic cortical (and sometimes subcortical) myoclonus, tonic–clonic seizures and ataxia. The specific identity of this system is currently unknown. However, it appears vulnerable to processes that involve intraneuronal storage (e.g. Lafora disease, ceroid lipofuscinoses, sialidosis), conditions that lead to neuronal degeneration via a number of mechanisms (Unverricht–Lundborg disease, MERRF, DRPLA), and now storage of extraneuronal material in AMRF can be added to this list. A fine rhythmic tremor as an early clinical feature of progressive myoclonus epilepsy is unusual. It could actually represent a form of cortical myoclonus, as has been described in benign familial adult myoclonic epilepsy (Sano et al., 2002), but detailed electrophysiological studies to test this in AMRF have not been done.
In the original description of AMRF, the renal pathology showed focal glomerulosclerosis in all four patients, with interstitial fibrosis in three of four patients (Andermann et al., 1986). Collapsing glomerulopathy appears to be typical in AMRF, and this is regarded as a severe variant of focal glomerulosclerosis (Detwiler et al., 1994; Meyrier, 1999). Collapsing glomerulopathy has been associated with hepatitis C, human immunodeficiency virus, autoimmune diseases and lymphoproliferative disorders, but is often idiopathic (Detwiler et al., 1994; Grcevska and Polenakovik, 1999; Laurinavicius et al., 1999; Meyrier, 1999; Singh et al., 2000). Familial cases have been mentioned briefly in the literature, and one family with probable recessive inheritance has been described recently (Avila-Casado et al., 2003). It now appears that AMRF represents a recessive form of collapsing glomerulopathy.
Focal glomerulosclerosis was previously thought to be sporadic, but recently many familial cases have been identified (Conlon et al., 1999). There is genetic heterogeneity, with both autosomal recessive types that usually present in childhood and autosomal dominant forms in adult life (Fuchshuber and Mehls, 2000; Kaplan and Pollak, 2001). Early childhood recessive forms include the congenital nephrotic syndrome of Finnish type due to mutations in the gene encoding nephrin on chromosome 19q (Kestila et al., 1998), and steroid-resistant nephrotic syndrome due to mutations in NPHS2, a gene encoding the glomerular protein podocin on chromosome 1q (Boute et al., 2000). Recessive mutations of the Wilms tumour gene (WT1) on chromosome 11 are usually associated with diffuse mesangial sclerosis, but focal segmental glomerulosclerosis is also seen. These patients may have Wilms tumour, male pseudo-hermaphroditism or other genital anomalies (Fuchshuber and Mehls, 2000). Five autosomal dominant loci are known. In some families, focal glomerulosclerosis is due to mutations in 
-actinin 4 on chromosome 19q (Kaplan et al., 2000); other families map to chromosomes 11q21–q22 (Winn et al., 1999), 1q25–q31 (Tsukaguchi et al., 2000), 11q24 (Prakash et al., 2003) and 9q31–q32 (Chung et al., 2003), but the genes await identification. The genes identified for focal glomerulosclerosis are thus candidates for AMRF.
What is remarkable in AMRF is that there is no visible storage in the kidney, yet there is prominent storage in the brain. Genes identified for glomerulopathies to date have been involved with the glomerular basement membrane and related proteins. We hypothesize that in this autosomal recessive disorder, the mutant protein is also expressed in the brain, but cannot be cleared effectively, leading to the peculiar form of brain storage.
In summary, it is important to recognize this condition and to treat the patients in a timely fashion with dialysis and renal transplantation since they can survive for a number of years with retained intellect. More effective treatment of myoclonus with drugs such as piracetam (Fedi et al., 2001) may improve their quality of life.
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Acknowledgements |
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We wish to thank the patients and their families for their cooperation, and Dr Robert Hjorth, Royal Melbourne Hospital, for allowing us to study his patient. This study was supported in part by a grant from The Canadian Institutes of Health Research (CIHR) to E.A.
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References |
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TopSummaryIntroductionMethodsResultsDiscussionReferences |
|---|
Ahonen RE. Peripheral neuropathy in uremic patients and in renal transplant recipients. Acta Neuropathol (Berl) 1981; 54: 43–53.[CrossRef][Medline]
Andermann E, Remillard GM, Goyer C, Blitzer L, Andermann F, Barbeau A. Genetic and family studies in Friedreich's ataxia. Can J Neurol Sci 1976; 3: 287–301.[Medline]
Andermann E, Andermann F, Carpenter S, Wolfe LS, Nelson R, Patry G, et al. Action myoclonus–renal failure syndrome: a previously unrecognized neurological disorder unmasked by advances in nephrology. Adv Neurol 1986; 43: 87–103.[Medline]
Avila-Casado MC, Vargas-Alarcon G, Soto ME, Hernandez G, Reyes PA, Herrera-Acosta J. Familial collapsing glomerulopathy: clinical, pathological and immunogenetic features. Kidney Int 2003; 63: 233–9.[CrossRef][Web of Science][Medline]
Berkovic SF, Andermann F, Carpenter S, Wolfe LS. Progressive myoclonus epilepsies: specific causes and diagnosis. N Engl J Med 1986; 315: 296–305.[Web of Science][Medline]
Berkovic SF, Carpenter S, Andermann F, Andermann E, Wolfe LS. Kufs' disease: a critical reappraisal. Brain 1988; 111: 27–62.
Berkovic SF, Cochius J, Andermann E, Andermann F. Progressive myoclonus epilepsies: clinical and genetic aspects. Epilepsia 1993; 34 Suppl 3: S19–30.[Web of Science][Medline]
Boute N, Gribouval O, Roselli S, Benessy F, Lee H, Fuchshuber A, et al. NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic syndrome. Nat Genet 2000; 24: 349–54.[CrossRef][Web of Science][Medline]
Carpenter S, Karpati G, Andermann F, Jacob JC, Andermann E. The ultrastructural characteristics of the abnormal cytosomes in Batten–Kufs' disease. Brain 1977; 100: 137–56.
Chung KW, Ferrell RE, Ellis D, Barmada M, Moritz M, Finegold DN, et al. African American hypertensive nephropathy maps to a new locus on chromosome 9q31–q32. Am J Hum Genet 2003; 73: 420–9.[CrossRef][Web of Science][Medline]
Conlon PJ, Lynn K, Winn MP, Quarles LD, Bembe ML, Pericak-Vance M, et al. Spectrum of disease in familial focal and segmental glomerulosclerosis. Kidney Int 1999; 56: 1863–71.[CrossRef][Web of Science][Medline]
Detwiler RK, Falk RJ, Hogan SL, Jennette JC. Collapsing glomerulopathy: a clinically and pathologically distinct variant of focal segmental glomerulosclerosis. Kidney Int 1994; 45: 1416–24.[Web of Science][Medline]
Fedi M, Reutens D, Dubeau F, Andermann E, D'Agostino D, Andermann F. Long-term efficacy and safety of piracetam in the treatment of progressive myoclonus epilepsy. Arch Neurol 2001; 58: 781–6.
Fuchshuber A, Mehls O. Familial steroid-resistant nephrotic syndromes: recent advances. Nephrol Dial Transplant 2000; 15: 1897–900.
Grcevska L, Polenakovik M. Collapsing glomerulopathy: clinical characteristics and follow-up. Am J Kidney Dis 1999; 33: 652–7.[Web of Science][Medline]
Horoupian DS, Ross RT. Pigment variant of neuronal ceroid-lipofuscinosis (Kufs' disease). Can J Neurol Sci 1977; 4: 67–75.[Web of Science][Medline]
Kaplan J, Pollak MR. Familial focal segmental glomerulosclerosis. Curr Opin Nephrol Hypertens 2001; 10: 183–7.[Web of Science][Medline]
Kaplan JM, Kim SH, North KN, Rennke H, Correia LA, Tong HQ, et al. Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. Nat Genet 2000; 24: 251–6.[CrossRef][Web of Science][Medline]
Kestila M, Lenkkeri U, Mannikko M, Lamerdin J, McCready P, Putaala H, et al. Positionally cloned gene for a novel glomerular protein—nephrin—is mutated in congenital nephrotic syndrome. Mol Cell 1998; 1: 575–82.[CrossRef][Web of Science][Medline]
Laurinavicius A, Hurwitz S, Rennke HG. Collapsing glomerulopathy in HIV and non-HIV patients: a clinicopathological and follow-up study. Kidney Int 1999; 56: 2203–13.[CrossRef][Web of Science][Medline]
Lockwood AH. Neurologic complications of renal disease. Neurol Clin 1989; 7: 617–27.[Web of Science][Medline]
Mahoney CA, Arieff AI. Uremic encephalopathies: clinical, biochemical, and experimental features. Am J Kidney Dis 1982; 2: 324–36.[Web of Science][Medline]
Marseille Consensus Group. Classification of progressive myoclonus epilepsies and related disorders. Ann Neurol 1990; 28: 113–6.[CrossRef][Web of Science][Medline]
Meyrier AY. Collapsing glomerulopathy: expanding interest in a shrinking tuft. Am J Kidney Dis 1999; 33: 801–3.[Web of Science][Medline]
Prakash S, Chung KW, Sinha S, Barmada M, Ellis D, Ferrell RE, et al. Autosomal dominant progressive nephropathy with deafness: linkage to a new locus on chromosome 11q24. J Am Soc Nephrol 2003; 14: 1794–803.
Sano A, Mikami M, Nakamura M, Ueno S, Tanabe H, Kaneko S. Positional candidate approach for the gene responsible for benign adult familial myoclonic epilepsy. Epilepsia 2002; 43 Suppl 9: 26–31.[CrossRef]
Singh HK, Baldree LA, McKenney DW, Hogan SL, Jennette JC. Idiopathic collapsing glomerulopathy in children. Pediatr Nephrol 2000; 14: 132–7.[CrossRef][Web of Science][Medline]
Stern C. Principles of human genetics. 2nd edn. San Francisco: W.H. Freeman; 1960. p. 134–9.
Thompson JS, Thompson MW. Genetics in medicine. Philadelphia: Saunders; 1966. p. 201–6.
Tsukaguchi H, Yager H, Dawborn J, Jost L, Cohlmia J, Abreu PF, et al. A locus for adolescent and adult onset familial focal segmental glomerulosclerosis on chromosome 1q25–31. J Am Soc Nephrol 2000; 11: 1674–80.
Winn MP, Conlon PJ, Lynn KL, Howell DN, Slotterbeck BD, Smith AH, et al. Linkage of a gene causing familial focal segmental glomerulosclerosis to chromosome 11 and further evidence of genetic heterogeneity. Genomics 1999; 58: 113–20.[CrossRef][Web of Science][Medline]
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