Prenatal diagnosis and genetic counseling in a case of spina bifida in a family with Waardenburg syndrome type I.
OBJECTIVE
Waardenburg syndrome type I (WS I) is an autosomal dominant inherited disorder with an incidence of 1:45,000 in Europe. Mutations within the PAX3 gene are responsible for the clinical phenotype ranging from mild facial features to severe malformations detectable in prenatal diagnosis.


METHODS
Here, we report a four-generation family with several affected members showing various symptoms of WS I. We diagnosed the syndrome first in a pregnant young woman; she was referred because of a spina bifida in prenatal diagnosis. We performed clinical genetic investigations and molecular genetic analysis in all available family members.


RESULTS
The phenotype displays a wide intra-familial clinical variability of pigmentary disturbances, facial anomalies and developmental defects. Molecular studies identified a novel splice site mutation within the PAX3 gene in intron 5 in all affected family members, but in none of the unaffected relatives.


CONCLUSIONS
This case demonstrates the prenatal diagnosis of spina bifida in a fetus which leads to the initial diagnosis of WS I. Further studies could identify a private splice site mutation within the PAX3 gene responsible for the phenotype in this family.
Kujat
Annegret
A
Institute of Human Genetics, Medical Faculty, University of Leipzig, Leipzig, Germany. annegret.kujat@medizin.uni-leipzig.de
Veith
Veit-Peter
VP
Faber
Renaldo
R
Froster
Ursula G
UG
D000022:Abortion, Spontaneous; D000293:Adolescent; D005260:Female; D005817:Genetic Counseling; D005838:Genotype; D005865:Gestational Age; D006801:Humans; D007438:Introns; D009154:Mutation; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics; D010375:Pedigree; D010641:Phenotype; D011247:Pregnancy; D022821:RNA Splice Sites; D016135:Spinal Dysraphism / Q000000981:diagnostic imaging / Q000235:genetics*; D016216:Ultrasonography, Prenatal; D014849:Waardenburg Syndrome / Q000235:genetics*
D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D022821:RNA Splice Sites