HHS Public Access Author manuscript Author Manuscript
North Afr Middle East Epilepsy J. Author manuscript; available in PMC 2015 September 23. Published in final edited form as: North Afr Middle East Epilepsy J. 2014 ; 3(5): 5–7.
Epilepsy genetics in Africa: challenges and future perspectives Guida Landouré, MD, PhD1, Youssoufa Maiga, MD2, Oumar Samassékou, MD, PhD3, Karamoko Nimaga, MD4, Mahamadou Traoré, PhD5, and Kenneth H. Fischbeck, MD6 1Service
de Neurologie, Centre Hospitalier Universitaire du Point “G”, Bamako, (Mali)
2Service
de Neurologie, Centre Hospitalier Universitaire de Gabriel Touré, Bamako, (Mali)
Author Manuscript
3Manitoba 4Clinique 5Service
Institute of cell Biology, Winnipeg, (Canada)
Dinandougou, Marakakoungo, Koulikoro, (Mali) de Cytogénétique et de Biologie Reproductive, INRSP, Bamako, (Mali)
6Neurogenetics
Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, (USA).
Abstract
Author Manuscript
Despite the diversity of the African population, genetic studies, of epilepsy in particular, have been limited, especially in sub-Saharan Africa. In recent years, with the regression of infectious diseases in developing countries, the focus has shifted more towards non communicable disorders. The prevalence of epilepsy in Africa is higher compared to other continents. Although this has been attributed to the high rate of infectious diseases, genetic contributions should not be ignored. Research in genetic epilepsy in Africa could well benefit from the decreasing cost of genetic analysis, and could contribute to further our knowledge on the spectrum of these diseases in Africa. The growing collaboration between African research institutions and those of developed countries offers a unique opportunity to boost research in Africa and improve our global understanding of human disease, thus leading to the development of better therapeutic approaches.
Keywords Epilepsy; Genetics; Africa
Author Manuscript
Introduction Epilepsy is a common disease, with a frequency ranging from 5 to 8 per 1,000 in developed countries [1]. Despite the low health coverage in the African population [2] and the stigma surrounding epilepsy limiting patient access to health care or self-report [3], Africa still has a higher frequency of epilepsy with a median prevalence of 15 per 1,000 [4]. Epilepsy is classified as symptomatic and idiopathic. As early as 1960, Lennox and Lennox, in a theory
[email protected]. Conflict of interest: some authors were supported by Award administered by the National Human Genome Research Institute/ NIH (see Acknowledgements).
Landouré et al.
Page 2
Author Manuscript
they called “epilepsy diathesis”, suggested a genetic contribution to epilepsy [5]. Later, family and twin studies showed the role of genetic factors in epilepsy [6,7]. In addition, the risk of epilepsy in first-degree relatives of individuals with idiopathic generalized epilepsy was found to be 8–12 % compared to approximately 0.5% in the general population, reinforcing the genetic contribution in epilepsy [6]. As our knowledge has evolved in recent years, idiopathic epilepsy has been found to be caused by or associated with genetic factors or influenced by genetic susceptibility. Single genes, mostly ion channels and neurotransmitters, were found to cause epilepsy as early as 1995 [8], opening a road to the understanding of the physiopathology of epilepsy. However, epilepsy does not always show the classical pattern of Mendelian disorders, suggesting that other, non-Mendelian genetic and environmental factors likely play a role in these diseases.
Author Manuscript
Epilepsy genetics in Africa Despite the advances in epilepsy genetics, Africa in general and sub-Saharan Africa in particular have been lagging in terms of genetic research of idiopathic epilepsy, largely because of the lack of expertise and funds; the rare reports about genes associated with epilepsy have been on symptomatic epilepsy involving multiple organs [9-12]. Researchers considered a genetic contribution in epilepsy in Africa decades ago [13], although no molecular investigation followed until recent years, and that in North African countries that have close ties with Europe [14-16]. With the cost of genetic testing and other genetic diagnosis tools such as whole genome and exome sequencing expected to be accessible to researchers studying the African population in the near future, establishing the genetic basis of epileptic syndromes in Africa will be possible.
Author Manuscript
The majority of genetic epileptic syndromes so far described are autosomal dominant [17]. The low prevalence of recessive epileptic syndromes may be due to the small sib number in studied populations, generally Europeans. Africa has a long tradition of intra-ethnic and consanguineous marriages, resulting in increased prevalence of autosomal recessive disorders. With a high rate of fertility in African women, family-based genetic epilepsy studies offer a unique opportunity for finding new genes and mutations that may be important to understanding brain development and the mechanism of epilepsy, and also open way to new therapeutics for common epilepsy. Consanguinity in Africa
Author Manuscript
The prevalence of consanguinity was found to be high in Africa, especially in North Africa [18,19]. A recent study in Mali done in medical students has shown that the prevalence of consanguinity is about 16% (unpublished). This prevalence may be underestimated since interviewed students may not be know their full family history or they may not represent well areas with higher consanguinity. In fact, our daily clinical practice revealed that many of our epileptic patients originate from regions with higher consanguinity, and a family history of the disease is often reported. However, due to the limited access to medical care and the stigma surrounding the disease, many patients or families do not seek health care, leading to an underestimation of the burden of disease. Unfortunately, African researchers
North Afr Middle East Epilepsy J. Author manuscript; available in PMC 2015 September 23.
Landouré et al.
Page 3
Author Manuscript
receive less support from their government and other organizations to reach patients and conduct research in epilepsy, and genetics in general is considered as sophisticated and unnecessary even by some health authorities or practitioners. In this setting, knowingly or not, physicians, especially neurologists and pediatricians, do not explore further the genetic link with their patients’ disease; their daily practice has been limited to providing medicine to stop seizures. In addition, many of them are not trained to investigate the genetic aspect of diseases for example by taking family histories and drawing pedigrees. Because of the high prevalence of infectious diseases in Africa, much of the focus of health authorities and international funding bodies is diverted towards these diseases; widening the gap between developed countries and Africa in genetic epilepsy research. Febrile seizures and most common phenotype of epilepsy
Author Manuscript Author Manuscript
Febrile seizures (FS) are the most common phenotype of epilepsy [17], and studies have linked these diseases to mutations in sodium channel and GABA receptor subunit genes [20,21]. However, to date no clear transmission pattern has been established. Investigating these diseases in populations with large sibships could help to improve the characterization of their clinical and genetic spectrum. Moreover, exploring the genetic basis of febrile seizures in Africa may lead to new genes and mutations that can be studied in other populations. These studies may also reveal susceptibility variants for febrile seizures and lead to preventive measures in populations at risk. In sub-Saharan Africa, because of endemic malaria, febrile seizures are often taken for cerebral malaria, limiting the search for other causes. Raising awareness about the possible genetic contribution among health care practitioners will help in defining the clinical spectrum of genetic epilepsy in this region of Africa. In recent years, an epilepsy research project was done in a rural area of Mali, and found that 29.9% of a subset of surveyed epileptic patients has a family history of the disease [22]. Extending such initiatives to other areas may help gather a large cohort for genome-wide association studies (GWAS) and exome sequencing studies. As African scientists trained abroad including neurologists, neurogeneticists, pediatric neurologists, and geneticists move back to their home countries, research teams are developing to implement clinical and basic genetic studies, and improve the management of these diseases in the continent. Because some genetic epilepsy syndromes have specific treatment, characterizing these diseases in the African population would help to alleviate health care costs by reducing unnecessary prescriptions. Funding bodies such as the National Institutes of Health (USA) and Welcome Trust (UK) are providing substantial support to African researchers through the Human Heredity and Health in Africa (H3Africa) project to boost genetic research in the continent.
Author Manuscript
Updates in genetics of epilepsy The expansion of new genotyping and sequencing technologies such as whole exome sequencing in the African continent will certainly enhance research opportunities in genetic epilepsy, which will in turn contribute to the global understanding of the molecular basis of these disorders and enable a targeted approach to their diagnosis and management. Extending genetic epilepsy studies to the African population may solve the complexity of phenotypegenotype correlations in these diseases. This would require a political and
North Afr Middle East Epilepsy J. Author manuscript; available in PMC 2015 September 23.
Landouré et al.
Page 4
Author Manuscript
financial engagement from health authorities and training for African physicians in the principles of basic clinical and genetic research.
Acknowledgements G.L., Y.M., O.S., and M.T. are supported by Award Number 1U01HG007044-01A1 administered by the National Human Genome Research Institute as part of the NIH Common Fund H3 Africa Initiative and K.H.F. by the Intramural Research Program of NINDS.
References
Author Manuscript Author Manuscript Author Manuscript
1. Forsgren, L. Epidemiology and prognosis of epilepsy and its treatment.. In: Shorvon, SD.; Perucca, E.; Fish, DR.; Dodson, WE., editors. The treatment of epilepsy. Blackwell Science; Oxford: 2004. p. 21-42. 2. WFN. Atlas: country resources for neurological disorders. 2004 3. Baskind R, Birbeck GL. Epilepsy-associated stigma in sub-Saharan Africa: The social landscape of a disease. Epilepsy Behav. 2005; 7:68–73. [PubMed: 15978874] 4. Preux PM, Tiemagni F, Fodzo L, Kandem P, Ngouafong P, Ndonko F, et al. Antiepileptic therapies in the Mifi Province in Cameroon. Epilepsia. 2000; 41:432–9. [PubMed: 10756409] 5. Lennox, WG.; Lennox, MA. Epilepsy and Related Disorders. Little, Brown; Boston: 1960. The Genetics of Epilepsy.. 6. Steinlein OK. Genes and mutations in human idiopathic epilepsy. Brain Dev. 2004; 26(4):213–8. [PubMed: 15130686] 7. Kjeldsen MJ, Corey LA, Solaas MH, Friis ML, Harris JR, Kyvik KO, et al. Genetic factors in seizures: a populationbased study of 47 626 US, Norwegian and Danish twin pairs. Twin Res Hum Genet. 2005; 8:38–147. 8. Steinlein OK, Mulley JC, Propping P, Wallace RH, Phillips HA, Sutherland GR, et al. A missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. Nat Genet. 1995; 11(2):201–3. [PubMed: 7550350] 9. Gouider R, Ibrahim S, Fredj M, Gargouri A, Saïdi H, Ouezzani R, et al. Unverricht-Lündborg disease: clinical and electrophysiologic study of 19 Maghreb families. Rev Neurol. 1998; 154(6-7): 503–7. [PubMed: 9773083] 10. Lohi H, Turnbull J, Zhao XC, Pullenayegum S, Ianzano L, Yahyaoui M, et al. Genetic diagnosis in Lafora disease: genotype-phenotype correlations and diagnostic pitfalls. Neurology. 2007; 68(13): 996–1001. [PubMed: 17389303] 11. Traoré M, Landouré G, Motley W, Sangaré M, Meilleur K, Coulibaly S, et al. Novel mutation in the NHLRC1 gene in a Malian family with a severe phenotype of Lafora disease. Neurogenetics. 2009; 10(4):319–23. [PubMed: 19322595] 12. Khiari HM, Lesca G, Malafosse A, Mrabet A. A novel exon 3 mutation in a Tunisian patient with Lafora's disease. J Neurol Sci. 2011; 304(1-2):136–7. [PubMed: 21371719] 13. Jilek-Aall L, Jilek W, Miller JR. Clinical and genetic aspects of seizure disorders prevalent in an isolated African population. Epilepsia. 1979; 20(6):613–22. [PubMed: 499114] 14. Abouda H, Hizem Y, Gargouri A, Depienne C, Bouteiller D, Riant F, et al. Familial form of typical childhood absence epilepsy in a consanguineous context. Epilepsia. 2010; 51(9):1889–93. [PubMed: 20561025] 15. Fendri-Kriaa N, Kammoun F, Rebai A, Kolsi D, Hadj Salem I, Fakhfakh F, et al. Genetic screening of two Tunisian families with generalized epilepsy with febrile seizures plus. Eur J Neurol. 2009; 16(6):697–704. [PubMed: 19236456] 16. Fendri-Kriaa N, Kammoun F, Salem IH, Kifagi C, Mkaouar-Rebai E, Hsairi I, et al. New mutation c.374C>T and a putative disease-associated haplotype within SCN1B gene in Tunisian families with febrile seizures. Eur J Neurol. 2011; 18(5):695–702. [PubMed: 21040232] 17. Nabbout R, Scheffer IE. Genetics of idiopathic epilepsies. Handb Clin Neurol. 2013; 111:567–78. [PubMed: 23622204] North Afr Middle East Epilepsy J. Author manuscript; available in PMC 2015 September 23.
Landouré et al.
Page 5
Author Manuscript
18. Cherkaoui Jaouad I, Chafaï Elalaoui S, Sbiti A, Elkerh F, Belmahi L, Sefiani A. Consanguineous marriages in morocco and the consequence for the incidence of autosomal recessive disorders. J Biosoc Sci. 2009; 41:575–81. [PubMed: 19433002] 19. Yamamah G, Abdel-Raouf E, Talaat A, Saad-Hussein A, Hamamy H, Meguid NA. Prevalence of consanguineous marriages in south Sinai, Egypt. J Biosoc Sci. 2013; 45(1):31–9. [PubMed: 22583662] 20. Wallace RH, Wang DW, Singh R, Scheffer IE, George AL Jr, Phillips HA, et al. Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B. Nat Genet. 1998; 19(4):366–70. [PubMed: 9697698] 21. Baulac S, Huberfeld G, Gourfinkel-An I, Mitropoulou G, Beranger A, Prud>homme JF, et al. First genetic evidence of GABA(A) receptor dysfunction in epilepsy: a mutation in the gamma2-subunit gene. Nat Genet. 2001; 28(1):46–8. [PubMed: 11326274] 22. Bruno E, Nimaga K, Foba I, Vignoles P, Genton P, Doumbo O, et al. Results of an action-research on epilepsy in rural Mali. PLoS One. 2012; 7(8):e44469. [PubMed: 22970109]
Author Manuscript Author Manuscript Author Manuscript North Afr Middle East Epilepsy J. Author manuscript; available in PMC 2015 September 23.
North Afr Middle East Epilepsy J. Author manuscript; available in PMC 2015 September 23. Published in final edited form as: North Afr Middle East Epilepsy J. 2014 ; 3(5): 5–7.
Epilepsy genetics in Africa: challenges and future perspectives Guida Landouré, MD, PhD1, Youssoufa Maiga, MD2, Oumar Samassékou, MD, PhD3, Karamoko Nimaga, MD4, Mahamadou Traoré, PhD5, and Kenneth H. Fischbeck, MD6 1Service
de Neurologie, Centre Hospitalier Universitaire du Point “G”, Bamako, (Mali)
2Service
de Neurologie, Centre Hospitalier Universitaire de Gabriel Touré, Bamako, (Mali)
Author Manuscript
3Manitoba 4Clinique 5Service
Institute of cell Biology, Winnipeg, (Canada)
Dinandougou, Marakakoungo, Koulikoro, (Mali) de Cytogénétique et de Biologie Reproductive, INRSP, Bamako, (Mali)
6Neurogenetics
Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, (USA).
Abstract
Author Manuscript
Despite the diversity of the African population, genetic studies, of epilepsy in particular, have been limited, especially in sub-Saharan Africa. In recent years, with the regression of infectious diseases in developing countries, the focus has shifted more towards non communicable disorders. The prevalence of epilepsy in Africa is higher compared to other continents. Although this has been attributed to the high rate of infectious diseases, genetic contributions should not be ignored. Research in genetic epilepsy in Africa could well benefit from the decreasing cost of genetic analysis, and could contribute to further our knowledge on the spectrum of these diseases in Africa. The growing collaboration between African research institutions and those of developed countries offers a unique opportunity to boost research in Africa and improve our global understanding of human disease, thus leading to the development of better therapeutic approaches.
Keywords Epilepsy; Genetics; Africa
Author Manuscript
Introduction Epilepsy is a common disease, with a frequency ranging from 5 to 8 per 1,000 in developed countries [1]. Despite the low health coverage in the African population [2] and the stigma surrounding epilepsy limiting patient access to health care or self-report [3], Africa still has a higher frequency of epilepsy with a median prevalence of 15 per 1,000 [4]. Epilepsy is classified as symptomatic and idiopathic. As early as 1960, Lennox and Lennox, in a theory
[email protected]. Conflict of interest: some authors were supported by Award administered by the National Human Genome Research Institute/ NIH (see Acknowledgements).
Landouré et al.
Page 2
Author Manuscript
they called “epilepsy diathesis”, suggested a genetic contribution to epilepsy [5]. Later, family and twin studies showed the role of genetic factors in epilepsy [6,7]. In addition, the risk of epilepsy in first-degree relatives of individuals with idiopathic generalized epilepsy was found to be 8–12 % compared to approximately 0.5% in the general population, reinforcing the genetic contribution in epilepsy [6]. As our knowledge has evolved in recent years, idiopathic epilepsy has been found to be caused by or associated with genetic factors or influenced by genetic susceptibility. Single genes, mostly ion channels and neurotransmitters, were found to cause epilepsy as early as 1995 [8], opening a road to the understanding of the physiopathology of epilepsy. However, epilepsy does not always show the classical pattern of Mendelian disorders, suggesting that other, non-Mendelian genetic and environmental factors likely play a role in these diseases.
Author Manuscript
Epilepsy genetics in Africa Despite the advances in epilepsy genetics, Africa in general and sub-Saharan Africa in particular have been lagging in terms of genetic research of idiopathic epilepsy, largely because of the lack of expertise and funds; the rare reports about genes associated with epilepsy have been on symptomatic epilepsy involving multiple organs [9-12]. Researchers considered a genetic contribution in epilepsy in Africa decades ago [13], although no molecular investigation followed until recent years, and that in North African countries that have close ties with Europe [14-16]. With the cost of genetic testing and other genetic diagnosis tools such as whole genome and exome sequencing expected to be accessible to researchers studying the African population in the near future, establishing the genetic basis of epileptic syndromes in Africa will be possible.
Author Manuscript
The majority of genetic epileptic syndromes so far described are autosomal dominant [17]. The low prevalence of recessive epileptic syndromes may be due to the small sib number in studied populations, generally Europeans. Africa has a long tradition of intra-ethnic and consanguineous marriages, resulting in increased prevalence of autosomal recessive disorders. With a high rate of fertility in African women, family-based genetic epilepsy studies offer a unique opportunity for finding new genes and mutations that may be important to understanding brain development and the mechanism of epilepsy, and also open way to new therapeutics for common epilepsy. Consanguinity in Africa
Author Manuscript
The prevalence of consanguinity was found to be high in Africa, especially in North Africa [18,19]. A recent study in Mali done in medical students has shown that the prevalence of consanguinity is about 16% (unpublished). This prevalence may be underestimated since interviewed students may not be know their full family history or they may not represent well areas with higher consanguinity. In fact, our daily clinical practice revealed that many of our epileptic patients originate from regions with higher consanguinity, and a family history of the disease is often reported. However, due to the limited access to medical care and the stigma surrounding the disease, many patients or families do not seek health care, leading to an underestimation of the burden of disease. Unfortunately, African researchers
North Afr Middle East Epilepsy J. Author manuscript; available in PMC 2015 September 23.
Landouré et al.
Page 3
Author Manuscript
receive less support from their government and other organizations to reach patients and conduct research in epilepsy, and genetics in general is considered as sophisticated and unnecessary even by some health authorities or practitioners. In this setting, knowingly or not, physicians, especially neurologists and pediatricians, do not explore further the genetic link with their patients’ disease; their daily practice has been limited to providing medicine to stop seizures. In addition, many of them are not trained to investigate the genetic aspect of diseases for example by taking family histories and drawing pedigrees. Because of the high prevalence of infectious diseases in Africa, much of the focus of health authorities and international funding bodies is diverted towards these diseases; widening the gap between developed countries and Africa in genetic epilepsy research. Febrile seizures and most common phenotype of epilepsy
Author Manuscript Author Manuscript
Febrile seizures (FS) are the most common phenotype of epilepsy [17], and studies have linked these diseases to mutations in sodium channel and GABA receptor subunit genes [20,21]. However, to date no clear transmission pattern has been established. Investigating these diseases in populations with large sibships could help to improve the characterization of their clinical and genetic spectrum. Moreover, exploring the genetic basis of febrile seizures in Africa may lead to new genes and mutations that can be studied in other populations. These studies may also reveal susceptibility variants for febrile seizures and lead to preventive measures in populations at risk. In sub-Saharan Africa, because of endemic malaria, febrile seizures are often taken for cerebral malaria, limiting the search for other causes. Raising awareness about the possible genetic contribution among health care practitioners will help in defining the clinical spectrum of genetic epilepsy in this region of Africa. In recent years, an epilepsy research project was done in a rural area of Mali, and found that 29.9% of a subset of surveyed epileptic patients has a family history of the disease [22]. Extending such initiatives to other areas may help gather a large cohort for genome-wide association studies (GWAS) and exome sequencing studies. As African scientists trained abroad including neurologists, neurogeneticists, pediatric neurologists, and geneticists move back to their home countries, research teams are developing to implement clinical and basic genetic studies, and improve the management of these diseases in the continent. Because some genetic epilepsy syndromes have specific treatment, characterizing these diseases in the African population would help to alleviate health care costs by reducing unnecessary prescriptions. Funding bodies such as the National Institutes of Health (USA) and Welcome Trust (UK) are providing substantial support to African researchers through the Human Heredity and Health in Africa (H3Africa) project to boost genetic research in the continent.
Author Manuscript
Updates in genetics of epilepsy The expansion of new genotyping and sequencing technologies such as whole exome sequencing in the African continent will certainly enhance research opportunities in genetic epilepsy, which will in turn contribute to the global understanding of the molecular basis of these disorders and enable a targeted approach to their diagnosis and management. Extending genetic epilepsy studies to the African population may solve the complexity of phenotypegenotype correlations in these diseases. This would require a political and
North Afr Middle East Epilepsy J. Author manuscript; available in PMC 2015 September 23.
Landouré et al.
Page 4
Author Manuscript
financial engagement from health authorities and training for African physicians in the principles of basic clinical and genetic research.
Acknowledgements G.L., Y.M., O.S., and M.T. are supported by Award Number 1U01HG007044-01A1 administered by the National Human Genome Research Institute as part of the NIH Common Fund H3 Africa Initiative and K.H.F. by the Intramural Research Program of NINDS.
References
Author Manuscript Author Manuscript Author Manuscript
1. Forsgren, L. Epidemiology and prognosis of epilepsy and its treatment.. In: Shorvon, SD.; Perucca, E.; Fish, DR.; Dodson, WE., editors. The treatment of epilepsy. Blackwell Science; Oxford: 2004. p. 21-42. 2. WFN. Atlas: country resources for neurological disorders. 2004 3. Baskind R, Birbeck GL. Epilepsy-associated stigma in sub-Saharan Africa: The social landscape of a disease. Epilepsy Behav. 2005; 7:68–73. [PubMed: 15978874] 4. Preux PM, Tiemagni F, Fodzo L, Kandem P, Ngouafong P, Ndonko F, et al. Antiepileptic therapies in the Mifi Province in Cameroon. Epilepsia. 2000; 41:432–9. [PubMed: 10756409] 5. Lennox, WG.; Lennox, MA. Epilepsy and Related Disorders. Little, Brown; Boston: 1960. The Genetics of Epilepsy.. 6. Steinlein OK. Genes and mutations in human idiopathic epilepsy. Brain Dev. 2004; 26(4):213–8. [PubMed: 15130686] 7. Kjeldsen MJ, Corey LA, Solaas MH, Friis ML, Harris JR, Kyvik KO, et al. Genetic factors in seizures: a populationbased study of 47 626 US, Norwegian and Danish twin pairs. Twin Res Hum Genet. 2005; 8:38–147. 8. Steinlein OK, Mulley JC, Propping P, Wallace RH, Phillips HA, Sutherland GR, et al. A missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. Nat Genet. 1995; 11(2):201–3. [PubMed: 7550350] 9. Gouider R, Ibrahim S, Fredj M, Gargouri A, Saïdi H, Ouezzani R, et al. Unverricht-Lündborg disease: clinical and electrophysiologic study of 19 Maghreb families. Rev Neurol. 1998; 154(6-7): 503–7. [PubMed: 9773083] 10. Lohi H, Turnbull J, Zhao XC, Pullenayegum S, Ianzano L, Yahyaoui M, et al. Genetic diagnosis in Lafora disease: genotype-phenotype correlations and diagnostic pitfalls. Neurology. 2007; 68(13): 996–1001. [PubMed: 17389303] 11. Traoré M, Landouré G, Motley W, Sangaré M, Meilleur K, Coulibaly S, et al. Novel mutation in the NHLRC1 gene in a Malian family with a severe phenotype of Lafora disease. Neurogenetics. 2009; 10(4):319–23. [PubMed: 19322595] 12. Khiari HM, Lesca G, Malafosse A, Mrabet A. A novel exon 3 mutation in a Tunisian patient with Lafora's disease. J Neurol Sci. 2011; 304(1-2):136–7. [PubMed: 21371719] 13. Jilek-Aall L, Jilek W, Miller JR. Clinical and genetic aspects of seizure disorders prevalent in an isolated African population. Epilepsia. 1979; 20(6):613–22. [PubMed: 499114] 14. Abouda H, Hizem Y, Gargouri A, Depienne C, Bouteiller D, Riant F, et al. Familial form of typical childhood absence epilepsy in a consanguineous context. Epilepsia. 2010; 51(9):1889–93. [PubMed: 20561025] 15. Fendri-Kriaa N, Kammoun F, Rebai A, Kolsi D, Hadj Salem I, Fakhfakh F, et al. Genetic screening of two Tunisian families with generalized epilepsy with febrile seizures plus. Eur J Neurol. 2009; 16(6):697–704. [PubMed: 19236456] 16. Fendri-Kriaa N, Kammoun F, Salem IH, Kifagi C, Mkaouar-Rebai E, Hsairi I, et al. New mutation c.374C>T and a putative disease-associated haplotype within SCN1B gene in Tunisian families with febrile seizures. Eur J Neurol. 2011; 18(5):695–702. [PubMed: 21040232] 17. Nabbout R, Scheffer IE. Genetics of idiopathic epilepsies. Handb Clin Neurol. 2013; 111:567–78. [PubMed: 23622204] North Afr Middle East Epilepsy J. Author manuscript; available in PMC 2015 September 23.
Landouré et al.
Page 5
Author Manuscript
18. Cherkaoui Jaouad I, Chafaï Elalaoui S, Sbiti A, Elkerh F, Belmahi L, Sefiani A. Consanguineous marriages in morocco and the consequence for the incidence of autosomal recessive disorders. J Biosoc Sci. 2009; 41:575–81. [PubMed: 19433002] 19. Yamamah G, Abdel-Raouf E, Talaat A, Saad-Hussein A, Hamamy H, Meguid NA. Prevalence of consanguineous marriages in south Sinai, Egypt. J Biosoc Sci. 2013; 45(1):31–9. [PubMed: 22583662] 20. Wallace RH, Wang DW, Singh R, Scheffer IE, George AL Jr, Phillips HA, et al. Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B. Nat Genet. 1998; 19(4):366–70. [PubMed: 9697698] 21. Baulac S, Huberfeld G, Gourfinkel-An I, Mitropoulou G, Beranger A, Prud>homme JF, et al. First genetic evidence of GABA(A) receptor dysfunction in epilepsy: a mutation in the gamma2-subunit gene. Nat Genet. 2001; 28(1):46–8. [PubMed: 11326274] 22. Bruno E, Nimaga K, Foba I, Vignoles P, Genton P, Doumbo O, et al. Results of an action-research on epilepsy in rural Mali. PLoS One. 2012; 7(8):e44469. [PubMed: 22970109]
Author Manuscript Author Manuscript Author Manuscript North Afr Middle East Epilepsy J. Author manuscript; available in PMC 2015 September 23.
