title: Hypospadias as a novel feature in spinal bulbar muscle atrophy.
abstract: 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.
authors.affiliation: Department of Women's and Children's Health and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden.|Pediatric Surgery, Astrid Lindgren Children's Hospital, CMM02, Karolinska University Hospital, SE-17176, Stockholm, Sweden.
authors.forename: Anna Skarin
authors.initials: AS
authors.lastname: Nordenvall
authors.affiliation: Department of Neurology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Paucar
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Lung and Allergy Unit, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Catarina
authors.initials: C
authors.lastname: Almqvist
authors.affiliation: Department of Paediatric Endocrinology, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Nordenström
authors.affiliation: Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.|Child and Adolescent Psychiatry Research Center, Stockholm, Sweden.
authors.forename: Louise
authors.initials: L
authors.lastname: Frisén
authors.affiliation: Department of Women's and Children's Health and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. agneta.nordenskjold@ki.se.|Pediatric Surgery, Astrid Lindgren Children's Hospital, CMM02, Karolinska University Hospital, SE-17176, Stockholm, Sweden. agneta.nordenskjold@ki.se.
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordenskjöld
mesh_terms: D006801:Humans; D007021:Hypospadias / Q000150:complications* / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D020966:Muscular Disorders, Atrophic / Q000150:complications* / Q000235:genetics; D015995:Prevalence; D011944:Receptors, Androgen / Q000235:genetics; D012042:Registries; D013548:Sweden / Q000453:epidemiology; D019680:Trinucleotide Repeat Expansion
chemical_list: C410798:AR protein, human; D011944:Receptors, Androgen
keywords: Androgen receptor; CAG expansion; Hypospadias; Spinal bulbar muscle atrophy