Spinal and bulbar muscle atrophy (SBMA) is an X-linked neuromuscular disorder
caused by CAG repeat expansions in the androgen receptor (AR) gene. The SBMA
phenotype consists of slowly progressive neuromuscular symptoms and
undermasculinization features as the result of malfunction of the AR. The latter
mainly includes gynecomastia and infertility. Hypospadias is also a feature of
undermasculinization with an underdeveloped urethra and penis; it has not been
described as part of the SBMA phenotype but has been suggested to be associated
with a prolonged CAG repeat in the AR gene. This study includes the first
epidemiologic description of the co-occurrence of hypospadias and SBMA in
subjects and their male relatives in Swedish population-based health registers,
as well as an additional clinical case. One boy with severe hypospadias was
screened for mutations in the AR gene and was found to have 42 CAG repeats in it,
which is in the full range of mutations causing SBMA later in life. We also
detected a maximum of four cases displaying the combination of SBMA and
hypospadias in our national register databases. This is the third case report
with hypospadias in association with CAG repeat expansions in the AR gene in the
full range known to cause SBMA later in life. Our findings suggest that
hypospadias may be an under diagnosed feature of the SBMA phenotype and we
propose that neurologists working with SBMA further investigate and report the
true prevalence of hypospadias among patients with SBMA.Swedish Research Council, K2012-64X-14506-10-5Stockholm City CouncilFoundation Frimurare Barnhuset in StockholmSwedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM), 340-2013-5867Accepte