Understanding and Preventing Violence, Volume 2: Biobehavioral Influences (1994)
Chapter: CHROMOSOMAL ANOMALIES
MENDELIAN DISORDERS
Molecular genetic studies of rare, well-defined disorders can elucidate basic physiologic mechanisms. Familial hypercholesterolemia, for example, unraveled aspects of lipoprotein receptor synthesis and transport. Are there any such exploitable models for human violence?
A search through Mendelian Inheritance in Man (MIM), a computerized data base of known or suspected heritable disorders, revealed eight disorders of potential relevance in the sense that the words ''aggression," "rage," "violence," or "antisocial" were mentioned in the MIM description. Table 1 lists these disorders, their current MIM numbers, and comments. Except for alcoholism, the genetics of which are unclear, the disorders are only tangentially associated with violence. An appropriate model disorder (e.g., one with presenting symptoms such as inexplicable rage) has yet to be described, although this feature was present in one sibship from a consanguineous mating for Urbach and Wiethe's disease (Newton et al., 1971). Although seizure disorders did not appear in the search, emotional lability is a typical feature of Unverricht and Lundborg myoclonus epilepsy (MIM number 254800), a form of seizure disorder found largely in Finland.
At the other extreme, the genetics of some rare phenotypes associated with violence (e.g., repetitive rapists, pedophiles) have never been studied. It is possible that heritable forms may be uncovered among these rare individuals and that molecular genetics may be used to elucidate basic mechanisms of violence.
A potentially important finding that emerged after this review was completed deserves mention. Brunner et al. (1993a,b) reported on a single, large Dutch kindred in which an unusual number of males were affected with moderate intellectual deficiency and aggression. The pattern of transmission was consistent with X-linkage and perfectly correlated with a deficiency in the gene for the enzyme monoamine oxidase-A. Studies on the frequency of this gene and its association with aggression in the general population have yet to be conducted.
CHROMOSOMAL ANOMALIES
The report by Jacobs et al. (1965) of a high prevalence of men with an extra Y chromosome (karyotypes 47,XYY and 48,XXYY) among incarcerated males sparked research (and debate) into the issue of whether supernumerary Y individuals are at high risk for
TABLE 1 Known or Suspected Genetic Disorders Associated With Aggression
|
Disorder |
MIM Numbera |
Comments |
|
Urocanase deficiency |
276880 |
Vaguely defined disorder; aggression noted in one pedigree. |
|
Gilles de la Tourette symptom |
137580 |
Neurologic disorder with involuntary motoric and vocal tics. Both aggression and self-mutilation have been reported, but neither is symptomatic of the disorder. |
|
Precocious puberty, male limited |
176410 |
Gonadotropin-independent gonadal testosterone secretion; male-limited, autosomal dominant transmission with onset of sexual precocity as early as 1 year; blockage of both androgen and estrogen synthesis was associated with a reduction of aggression in a series of nine boys. |
|
a-Mannosidosis |
248500 |
Aggressive tendency noted in cattle with a-mannosidase deficiency, but not known to be associated with the deficiency in humans. |
|
Alcoholism |
103780 |
Not known to follow strict Mendelian transmission patterns; well-established phenotypic correlation with aggression. |
|
Lipoid proteinosis of Urbach and Wiethe |
247100 |
One pedigree reported in which a sib suffered with attacks of rage. |
|
Deafness-hypogonadism syndrome |
304350 |
Only a single pedigree reported, consistent with X linkage; antisocial and immature behavior noted in males of the pedigree. |
|
Fragile X syndrome |
309550 |
Variable expression with frequent mental retardation; antisocial tendencies noted but not a central part of the syndrome. |
|
a Mendelian Inheritance in Man. |
||
