A Bomford

EH Hanson

LP Kate Ten

English

PubMed

Leo P. ten Kate

Springer - Publisher Connector

LETTER TO THE EDITOR
Psychomotor developmental delay and epilepsy
in an offspring of father–daughter incest: quantification
of the causality probability
Leo P. ten Kate
Received: 27 March 2009 /Accepted: 15 July 2009 /Published online: 11 August 2009
# The Author(s) 2009. This article is published with open access at Springerlink.com
Schmidtke and Krawczak [1] described a patient with
developmental delay and epilepsy who was the offspring of
father–daughter incest, and showed that, based on available
medical records and the baseline risk of the disorder in the
population, the probability that the incest was causal for her
disorder exceeded the 50% cutoff above which she would
be entitled to a lifelong pension under the German federal
act of victim indemnification. Their case was complicated
by the absence of a clear specific diagnosis and the absence
of permission for diagnostic workup.
This letter is not meant to criticize their calculations
but to expand their work and cover other, less
complicated cases. One of the possibilities the authors
mention in their case report is a diagnosis of an
autosomal recessive infantile epilepsy syndrome. It is
easily shown that this diagnosis and, in fact, every
diagnosis of an autosomal recessive disorder in the
offspring of father–daughter incest is associated with a
probability over 50% that the incest was causal for the
disorder in the offspring. This also applies to a wide
range of consanguineous matings whether incestuous or
not.
The frequency of an autosomal recessive disorder in the
offspring of a consanguineous mating is given by the
formula
P1 ¼ Fqþ 1 Fð Þq2
in which F is the probability for autozygosity at the relevant
gene locus and q is the population frequency of a
pathogenetic allele at this gene locus. F, which is also
called the inbreeding coefficient, is one fourth in father–
daughter incest, one eighth in grandfather–granddaughter
incest, and 1/16 in a first-cousin union.
In this formula, the first part (Fq) denotes the absolute
probability that the disorder occurs as a result of the
consanguinity of the parents, while the second part, [(1-F)
q2], represents the absolute probability that the disorder was
not a consequence of the consanguinity but of another
cause [2]. So, the relative probability that a recessive
disorder in the offspring of a consanguineous union is
causally related to the consanguinity of the parents is
P2 ¼ Fq= Fqþ 1 Fð Þq2
 
When F=1/4, the critical value of q is 1/3, which means
that P2 is only smaller than 50% when q is greater than 1/3.
To the best of my knowledge, such high values of q do not
exist in the general population for pathogenetic alleles
causing autosomal recessive disorders. One of the highest
known values is the allele frequency in the case of
hemochromatosis, but this is still below 10% [3, 4].
In general, alleles causing an autosomal recessive
disease are rare. The allele frequency of cystic fibrosis,
which is one of the most common recessive disorders, is
generally quoted as being 1/50. At this allele frequency, the
probability that cystic fibrosis in an offspring of father–
daughter incest is the result of this incestuous union is 94%.
For grandfather–granddaughter incest, this falls to 88%. In
a first-cousin union, it is 77%. With smaller allele
frequencies, these percentages become higher.
L. P. ten Kate (*)
Department of Clinical Genetics and Institute for Health and Care
Research (EMGO+), VU University Medical Center,
Amsterdam, The Netherlands
e-mail: lp.tenkate@vumc.nl
Int J Legal Med (2010) 124:667–668
DOI 10.1007/s00414-009-0364-5
The calculations presented here are not new. However,
they illustrate the point that having a clear specific
diagnosis results in greater certainty about the causality
relation, although this may not always be favorable for the
patient claiming victim indemnification.
Open Access This article is distributed under the terms of the
Creative Commons Attribution Noncommercial License which per-
mits any noncommercial use, distribution, and reproduction in any
medium, provided the original author(s) and source are credited.
References
1. Schmidtke J, Krawczak M (2009) Psychomotor developmental
delay and epilepsy in an offspring of father-daughter incest:
quantification of the causality probability. Int J Legal Med.
doi:10.1007/s00414-009-0337-8
2. Ten Kate LP, Scheffer H, Cornel MC, van Lookeren Campagne JG
(1991) Consanguinity sans reproche. Hum Genet 86(3):295–296
3. Hanson EH, Imperatore G, Burke W (2001) HFE gene and
hereditary hemochromatosis: a HuGE review. Human genome
epidemiology. Am J Epidemiol 154:193–206
4. Bomford A (2002) Genetics of haemochromatosis. Lancet
360:1673–1681
668 Int J Legal Med (2010) 124:667–668


Psychomotor developmental delay and epilepsy in an offspring of father–daughter incest: quantification of the causality probability

ten Kate, L.P.

NARCIS 

Psychomotor developmental delay and epilepsy in an offspring of father-daughter incest: quantification of the causality probability

MUCC (Crossref)

Consanguinity sans reproche.

Genetics of haemochromatosis.

HFE gene and hereditary hemochromatosis: a HuGE review. Human genome epidemiology.

Psychomotor developmental delay and epilepsy in an offspring of father-daughter incest: quantification of the causality probability.

file:///data/core-remote/dit/data/Springer-OA/pdf/4f2/aHR0cDovL2xpbmsuc3ByaW5nZXIuY29tLzEwLjEwMDcvczAwNDE0LTAwOS0wMzY0LTUucGRm.pdf

Psychomotor developmental delay and epilepsy in an offspring of father–daughter incest: quantification of the causality probability

Abstract

Similar works

Full text

Available Versions

Springer - Publisher Connector

NARCIS

MUCC (Crossref)

Springer - Publisher Connector