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A rare, non-syndromic, congenital, urogenital tract malformation affecting males and characterized by penoscrotal, scrotal or perineal displacement of the urethral meatus, and commonly associated with curvation of the penis. The scrotum might appear bifid in severe cases, and the boy can also have a micropenis.
ORPHA:95706Classification level: Disorder
- Hypospadias, severe form
- Perineal, scrotal or penoscrotal hypospadias
- Prevalence: Unknown
- Inheritance: Autosomal dominant or Autosomal recessive or X-linked recessive
- Age of onset: Antenatal, Neonatal
- ICD-10: Q54.2 Q54.3
- OMIM: 146450 300633 300758 300856
- UMLS: -
- MeSH: -
- GARD: -
- MedDRA: -
Posterior hypospadias occurs in about 5% to 9% of hypospadias, for which the mean birth prevalence is estimated to be 1/500 in Europe.
The consequences of hypospadias, apart from the appearance, include spraying of the urinary stream, inability to urinate in standing position, and later in life curvature, unless corrected, leads to difficulties during intercourse. Fertility problems and decreased satisfaction with genital appearance are more common. Severe hypospadias and concomitant undescended testis, is regarded as a disorder of sex development (DSD) and should be referred to special multidisciplinary teams for molecular and hormonal evaluation.
Posterior hypospadias arises early during urethra development in fetal weeks 8-16. The malformation is generally considered ''complex'' with both a genetic and environmental background. To date, the two genes MAMLD1 (Xq28) and AR (Xq12) have been associated with the isolated form of posterior hypospadias. However, there are an increasing number of genes involved in sex development that may lead to hypospadias, either as a part of syndrome or a result of gonadal dysgenesis.
The diagnosis is set by an external inspection of the penis, usually just after birth. Hormonal, genetic and anatomic evaluations are required when the hypospadias is part of a DSD.
Differential diagnoses include congenital adrenal hyperplasia in girls and, in patients with an XY karyotype, androgen insensitivity syndrome, steroid 5-alpha-reductase deficiency and 17-beta-hydroxysteroid dehydrogenase 3 deficiency. In addition, infants are screened for WT1 mutations to exclude Denys-Drash syndrome.
Ultrasound diagnosis is sometimes possible since the tip of the penis can be smaller and quadrangular.
The familial recurrence risk is difficult to determine due to the complex genetic and environmental factors involved; however, genetic counseling is recommended. For hypospadias in general, the risk that a brother of an affected boy will also have hypospadias is 9-17%. The risk for the next boy in a family with an affected father and son is 25%. Where MAMLD1 is responsible, mutations may occur sporadically or through X-linked inheritance.
Management and treatment
Current guidelines consider optimal age for hypospadias repair between 9 and 18 months, depending on the severity and the need for multiple procedures. Surgery for posterior hypospadias remains challenging and no single technique is applicable to all patients. Patients frequently require extra tissue to restore the missing urethra after correction of the curvature, usually the inner prepuce or, in redo surgery, buccal mucosal is used. Affected males should be followed up into adulthood by a urologist or andrologist.
There is a greater dissatisfaction with the genital appearance in patients treated for posterior and complex hypospadias. Lower urinary tract symptoms are common postoperatively. Sexual problems like anejaculation are more common in posterior hypospadias; although fertility is diminished, sexual life is generally regarded as satisfactory.