Heredity of hypospadias and the significance of low birth weight.
OBJECTIVE
We analyzed a large group of patients with hypospadias regarding familial aggregation, phenotype, twin rate and ethnic origin and assessed the correlation of low birth weight with hypospadias.


METHODS
We mailed questionnaires to 2,503 boys operated on for hypospadias in Sweden asking for additional cases of hypospadias in the family, the number of brothers in the nuclear family, and birth weight of the boys with hypospadias and their brothers.


RESULTS
Of the boys 7% reported 1 or more additional family members with hypospadias. The birth weight of the boys with hypospadias was significantly lower (p = 5 x 10-13) than the birth weight of their unaffected brothers. Phenotyping of 676 individuals revealed glandular hypospadias in 53%, penile forms in 39%, penoscrotal or perineal variants in 6% and cleaved prepuce as the only manifestation in 2%. There were 50% more twins than expected compared to the general population and established zygosity in 83% (67% monozygotic, 33% dizygotic). Non-Swedish ethnicity was noted in 22% of the subjects, a third of whom were from Middle Eastern countries.


CONCLUSIONS
We present data on heredity, birth weight, phenotype and ethnic origin in a large group of patients with hypospadias. The finding of additional members with hypospadias in 7% of the families supports the concept that genetic factors are involved in the pathogenesis. The strong association with low birth weight may be explained by genetic and environmental factors.
Fredell
Louise
L
Department of Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.
Kockum
Ingrid
I
Hansson
Einar
E
Holmner
Staffan
S
Lundquist
Lars
L
Läckgren
Göran
G
Pedersen
Jörgen
J
Stenberg
Arne
A
Westbacke
Gunnar
G
Nordenskjöld
Aneta
A
D001724:Birth Weight; D006801:Humans; D007021:Hypospadias / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D010375:Pedigree; D010641:Phenotype; D012042:Registries; D013548:Sweden / Q000453:epidemiology