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A novel duplication in the HOXA13 gene in a family with atypical hand-foot-genital syndrome
  1. L Frisén1,
  2. K Lagerstedt1,
  3. M Tapper-Persson1,
  4. I Kockum1,
  5. A Nordenskjöld1,2
  1. 1Department of Molecular Medicine, Karolinska Institutet, Karolinska Hospital, SE-17176 Stockholm, Sweden
  2. 2Department of Women and Child Health, Astrid Lindgren Children Hospital, Karolinska Hospital, SE-17176 Stockholm, Sweden
  1. Correspondence to:
 Dr A Nordenskjöld, Department of Molecular Medicine, CMM:02, Karolinska Hospital, SE-171 76 Stockholm, Sweden; 

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Hypospadias, when the urethral opening is located on the ventral side of the penis, is one of the most common congenital malformations with an incidence of 3 per 1000 males.1 Hypospadias is considered a complex trait caused by several genetic and environmental factors; low birth weight, for example, is associated with an increased risk for hypospadias.2–5 Most cases of hypospadias are sporadic but about 10% of the boys have a relative with the malformation.4,6–9 There are families with an autosomal dominant inheritance pattern of hypospadias.4,10 Hypospadias is also a manifestation in some rare single gene traits affecting sex differentiation, for example, the X linked partial androgen insensitivity syndrome and the recessive 5-alpha-reductase deficiency.11–13 However, these syndromes are characterised by severe hypospadias in association with other genital malformations such as cryptorchidism, bifid scrotum, and penoscrotal transposition.

Hand-foot-genital syndrome (HFGS) is an autosomal dominant syndrome that may include hypospadias.14,15 HFGS is characterised by skeletal anomalies and urogenital malformations. The skeletal manifestations affect the distal limbs and include short, proximally placed thumbs with hypoplastic thenar eminences, ulnar deviation of the second finger, clinodactyly of the fifth finger, short, medially deviated halluces, brachydactyly of the second to fifth toes, and shortening of the carpals and tarsals. Typical urogenital abnormalities in females are bicornuate uterus, vaginal septum, and ectopic localisation of ureteric and urethral orifices. Vesicoureteral reflux and ureteropelvic obstruction has been observed in females as well as in males.16 The syndrome was initially called hand-foot-uterus syndrome by Stern et al,17 but the observation of hypospadias in some affected males prompted the change of nomenclature.18,19

Key points

  • Hypospadias, when the meatus is located on the ventral side of the penis, is a common malformation with genetic and environmental …

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