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Genetic Analysis of Kifafa, a Complex Familial Seizure Disorder
Rosalind J. Neuman,' Jennifer M. Kwon,' Louise Jilek-Aall,2 Henry T. Rwiza,3 John P. Rice,'
and Paul J. Goodfellow'
'Washington University School of Medicine, St. Louis; 2University of British Columbia, Vancouver; and 3Muhimbili Medical Centre,
Dar-es-Salaam, Tanzania
Summary Introduction
Kifafa is the Swahili name for an epileptic seizure disorder, first reported in the early 1960s, that is prevalent in the Wapogoro tribe of the Mahenge region of Tanzania in
eastern Africa. A 1990 epidemiological survey of seizure disorders in this region reported a prevalence in the range of 19/1,i000-36/1,000, with a mean age at onset of 11.6 years; 80% of those affected had onset prior to 20 years of age. A team of investigators returned to Tanzania in 1992 and collected data on 1,600 relatives of 26 probands in 20 kifafa families. We have undertaken a genetic analysis of these data in order to detect the presence of
familial clustering and whether such aggregation could be attributed to genetic factors. Of the 127 affected individuals in these pedigrees, 23 are first-degree relatives (parent, full sibling, or offspring) of the 26 probands; 20 are second-degree relatives (half-sibling, grandparent, uncle, or aunt). When corrected for age, the risk to first-degree relatives
is .15; the risk to second-degree relatives is .063. These risks are significantly higher than would be expected if there were no familial clustering. Segregation analysis,
using PAP (rev.4.0), was undertaken to clarify the mode of inheritance. Among the Mendelian single-locus models,
an additive model was favored over either a dominant, recessive, or codominant model. The single-locus model
could be rejected when compared with the mixed Mendelian model (inclusion of a polygenic background), although
the major-gene component tends to be recessive. However, the hypothesis of Mendelian transmission could be rejected, suggesting that, although kifafa does aggregate in these families, the mode of inheritance is genetically complex. Received December 13, 1994; accepted for publication July 24, 1995.
Address for correspondence and reprints: Dr. Rosalind J. Neuman,
Department of Psychiatry, Washington University School of Medicine,
4940 Children's Place, St. Louis, MO 63110.
© 1995 by The American Society of Human Genetics. All rights reserved.
0002-9297/95/5704-0022$02.00
In the early 1960s, while working as a physician in a rural area of Tanzania, L. Jilek-Aall reported the existence
of a seizure disorder among the Wapogoro tribe of the Mahenge mountain region of Tanzania (Jilek-Aall 1965). This disorder, known in Swahili as kifafa (a word that denotes "being half dead and rigid" [Jilek-Aall et al. 1979]), was characterized by sudden falling into unconsciousness and convulsive movements and clinically
was categorized as a paroxysmal phenomenon of an epileptic nature. Oddly, kifafa was also characterized by burns on many parts of the body, burns usually acquired by falling into an open domestic fire because of the reluctance on the part of family members to rescue the epileptic. To understand this behavior it must be realized thatbefore the introduction of western medical knowledge an epileptic seizure was considered a catastrophe for the family (Jilek-Aall 1965). An epileptic was treated with extreme cruelty and neglect by both family and friends; epilepsy was regarded as something frightening and inexplicable,
perhaps even caused by an evil spirit. Therefore, "if an epileptic falls into the fire, nobody dares to pull him out again" (Jilek-Aall et al. 1965, p. 64). Hence burns are significant for the diagnosis of epilepsy. In conjunction with efforts of the nurses at a longstanding Catholic mission and many volunteers, the Mahenge Clinic for kifafa was established around 1960, to
provide both education and medical treatment for the seizure disorder. Clinical histories and physical examinations were performed on 200 patients, many of whom began taking moderate daily doses of phenobarbital
(Jilek-Aall et al. 1979). The success of that program in reducing seizures was attested to by the consistently
increasing numbers of patients from the area who sought treatment. "Although mortality among kifafa patients
was relatively high, the majority of those receiving antiepileptic
medication from the Mahenge Clinic remained free of attacks for extended periods, some for several years" (Jilek-Aall et al. 1979, p. 616).
A 30-year follow-up study of the Wapogoro tribe was conducted by Jilek-Aall in 1990, the outcome of which
was reported in 1992 (Jilek-Aall and Rwiza 1992). With 902 Neuman et al.: Genetic Analysis of Kifafa the help of one of the original missionary sisters, local health personnel, former epilepsy patients, village leaders, Catholic priests and nuns, and a search of the church registry, the locations of many of the clinic's kifafa patients,
first examined in the early 1960s, were traced. Of the 164 patients originally treated with antiepileptic drugs, 36 were still alive; 24 reported themselves as seizure free.
Rosalind J. Neuman,' Jennifer M. Kwon,' Louise Jilek-Aall,2 Henry T. Rwiza,3 John P. Rice,'
and Paul J. Goodfellow'
'Washington University School of Medicine, St. Louis; 2University of British Columbia, Vancouver; and 3Muhimbili Medical Centre,
Dar-es-Salaam, Tanzania
Summary Introduction
Kifafa is the Swahili name for an epileptic seizure disorder, first reported in the early 1960s, that is prevalent in the Wapogoro tribe of the Mahenge region of Tanzania in
eastern Africa. A 1990 epidemiological survey of seizure disorders in this region reported a prevalence in the range of 19/1,i000-36/1,000, with a mean age at onset of 11.6 years; 80% of those affected had onset prior to 20 years of age. A team of investigators returned to Tanzania in 1992 and collected data on 1,600 relatives of 26 probands in 20 kifafa families. We have undertaken a genetic analysis of these data in order to detect the presence of
familial clustering and whether such aggregation could be attributed to genetic factors. Of the 127 affected individuals in these pedigrees, 23 are first-degree relatives (parent, full sibling, or offspring) of the 26 probands; 20 are second-degree relatives (half-sibling, grandparent, uncle, or aunt). When corrected for age, the risk to first-degree relatives
is .15; the risk to second-degree relatives is .063. These risks are significantly higher than would be expected if there were no familial clustering. Segregation analysis,
using PAP (rev.4.0), was undertaken to clarify the mode of inheritance. Among the Mendelian single-locus models,
an additive model was favored over either a dominant, recessive, or codominant model. The single-locus model
could be rejected when compared with the mixed Mendelian model (inclusion of a polygenic background), although
the major-gene component tends to be recessive. However, the hypothesis of Mendelian transmission could be rejected, suggesting that, although kifafa does aggregate in these families, the mode of inheritance is genetically complex. Received December 13, 1994; accepted for publication July 24, 1995.
Address for correspondence and reprints: Dr. Rosalind J. Neuman,
Department of Psychiatry, Washington University School of Medicine,
4940 Children's Place, St. Louis, MO 63110.
© 1995 by The American Society of Human Genetics. All rights reserved.
0002-9297/95/5704-0022$02.00
In the early 1960s, while working as a physician in a rural area of Tanzania, L. Jilek-Aall reported the existence
of a seizure disorder among the Wapogoro tribe of the Mahenge mountain region of Tanzania (Jilek-Aall 1965). This disorder, known in Swahili as kifafa (a word that denotes "being half dead and rigid" [Jilek-Aall et al. 1979]), was characterized by sudden falling into unconsciousness and convulsive movements and clinically
was categorized as a paroxysmal phenomenon of an epileptic nature. Oddly, kifafa was also characterized by burns on many parts of the body, burns usually acquired by falling into an open domestic fire because of the reluctance on the part of family members to rescue the epileptic. To understand this behavior it must be realized thatbefore the introduction of western medical knowledge an epileptic seizure was considered a catastrophe for the family (Jilek-Aall 1965). An epileptic was treated with extreme cruelty and neglect by both family and friends; epilepsy was regarded as something frightening and inexplicable,
perhaps even caused by an evil spirit. Therefore, "if an epileptic falls into the fire, nobody dares to pull him out again" (Jilek-Aall et al. 1965, p. 64). Hence burns are significant for the diagnosis of epilepsy. In conjunction with efforts of the nurses at a longstanding Catholic mission and many volunteers, the Mahenge Clinic for kifafa was established around 1960, to
provide both education and medical treatment for the seizure disorder. Clinical histories and physical examinations were performed on 200 patients, many of whom began taking moderate daily doses of phenobarbital
(Jilek-Aall et al. 1979). The success of that program in reducing seizures was attested to by the consistently
increasing numbers of patients from the area who sought treatment. "Although mortality among kifafa patients
was relatively high, the majority of those receiving antiepileptic
medication from the Mahenge Clinic remained free of attacks for extended periods, some for several years" (Jilek-Aall et al. 1979, p. 616).
A 30-year follow-up study of the Wapogoro tribe was conducted by Jilek-Aall in 1990, the outcome of which
was reported in 1992 (Jilek-Aall and Rwiza 1992). With 902 Neuman et al.: Genetic Analysis of Kifafa the help of one of the original missionary sisters, local health personnel, former epilepsy patients, village leaders, Catholic priests and nuns, and a search of the church registry, the locations of many of the clinic's kifafa patients,
first examined in the early 1960s, were traced. Of the 164 patients originally treated with antiepileptic drugs, 36 were still alive; 24 reported themselves as seizure free.
Submitted on July 28, 2010 in By David.
