Background: Partial androgen insensitivity syndrome (PAIS) covers a large spectrum of phenotypes, with the common denominator being insufficient virilisation of the external genitalia in an XY child with normal testosterone (T) production. Genetic diagnosis of PAIS is based on the identification of an androgen receptor (AR) gene mutation.
Aim: The aim of this work was to determine whether the PAIS-like phenotype is associated with other gene mutations.
Methods: During the last few years, we had the opportunity to perform molecular analyses of 200 children diagnosed with PAIS-like syndrome.
Results: An AR gene mutation was identified in only 15% of the cases, confirming the PAIS. In five cases, 5-alpha reductase deficiency was responsible for the undervirilisation. An SF1 mutation was identified in three cases. Three patients presenting undervirilisation were found to have a WT1 gene mutation. In a group of 70 infants with a severe form of PAIS-like syndrome, we identified two MAMLD1 gene mutations and three polymorphisms.
Conclusions: The diagnosis of PAIS as a syndrome requires the identification of an AR gene mutation. Undervirilisation of XY patients with normal plasma T should not be limited to analysis of the AR gene, as PAIS-like syndrome may be symptom of another clinical form of 46,XY DSD, such an 5-alpha reductase deficiency, or SF1, WT1, or MAMLD1 gene mutation.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology