P32
PERINATAL AND INFANT DEATHS IN FAMILIES OF GIRLS WITH RETT SYNDROME
Fyfe S1, Leonard H2,3, Dye D1, Leonard S2
1Curtin University of Technology
2TVW Telethon Institute for Child Health Research.
3Disability Services Commission, Western Australia
Background: Rett Syndrome (RS) is a neurodevelopmental disorder which occurs predominantly
in girls and results in severe physical and intellectual handicap. Hyperventilation and breath holding
are characteristic symptoms of the disorder and sudden death in children with Rett syndrome has
been likened to SIDS. Although the majority of cases are sporadic, current consensus is that RS is
genetic because of its gender specificity, the small number of familial cases and the concordance in
monozygotic twins. A popular mechanism is an X linked dominant disorder , lethal in males.
However if the vast majority of new cases are sporadic new mutations, no increase in fetal wastage in
mothers of Rett syndrome girls or distortion of the sibling sex ratio would be apparent. This is
consistent with the limited evidence so far. Killian (1986) found normal male:female ratio and that the
proportion of miscarriages and stillbirths were within the normal range. However, these results are
based on pooled data which were not representative of the population from which they were derived
and there was no control population. Interpretation of these results is therefore limited
Aims of the Study: The aims of the case control study relevant to this paper were to investigate :
1. fetal wastage as indicated by reported miscarriage and stillbirth prevalence
2. the prevalence and cause of reported neonatal and infant death.
Methods: A family history study design was used. Pedigree data were collected by questionnaire
from parents of 104 case probands representing 79.4 % of the Australian juvenile RS population in
April 1995. During 1996 pedigree data were collected in an identical fashion from a control population.
Proportions and odds ratios were calculated.
Key Findings: There was no disturbance in the male:female ratio in RS families. A higher proportion
of stillbirths and neonatal deaths was reported in RS families but did not reach significance (OR=1.54,
95%CI 0.88-2.61). However, stillbirths in case families were almost double the level in control families
(OR=1.89, 95% CI 0.93-3.78). Stillbirths and neonatal deaths more commonly affected male offspring
in the parental and proband generations of case families (19/30) than in control families (10/21).
Interestingly perinatal loss was more common on the maternal side of Rett syndrome families than in
control families (p=0.011). Childhood deaths also occurred more commonly in Rett syndrome families
with the difference almost reaching significance (OR=1.78, 95%CI 0.99-3.22). SIDS was reported in 3
siblings of Rett Syndrome probands but in no control siblings.
Conclusions: These results suggest that perinatal loss may be higher in families of girls with Rett
syndrome and that these deaths are occurring more commonly in males on the maternal side of the
family. However as the number of deaths is small there is little effect on the gender ratio. Confirmation
of this pattern of perinatal loss may indicate an alternative expression of the Rett syndrome gene.
Therefore it is important to extend this investigation to a larger population in order to provide the
statistical power needed to confirm or refute the findings of this study.
Killian, W (1986) On the genetics of Rett syndrome:analysis of family and pedigree data.
Genetics, 24, 369-376.
American Journal of Medical