Endocrine Abstracts

Introduction: 46XY gonadal dysgenesis is one of the important cause of DSD with varied clinical presentation Genetic mutations like SRY, NR5A1, SOX9, DHX37 are common mutations that can cause gonadal dysgenesis. Genetic testing for reaching final diagnosis in 46 XY DSD is increasingly playing a crucial role in the management plan.

Case: A 10-month-old patient presented in our DSD clinic with complaint of atypical genitalia which were noticed at birth. The child was a product of consanguineous marriage. Initial rearing was female but at 2 months of age the sex of rearing was changed to male. There was no history of virilization or maternal drug intake during pregnancy. The child was developmentally normal with no abnormal findings. Anthropometric parameters were normal. On genital examination the genitalia were asymmetrical and EMS score was 4. The patient had micropenis, right gonad was absent and left was present in the inguinal region.On ultrasound the right gonad (0.3×0.5 cm) was present peritoneally and left gonad was present in the mid-inguinal region (0.6×0.3 cm). Karyotype was 46XY with satellites on chromosome 15 and 22. AMH was low and testosterone levels initially normal. On HCG stimulation there was a blunted response with normal stimulated T/DHT ratio. Mullerian duct remnants was demonstrated in genitogram. MRI brain was normal.Genetic panel for 46XY DSD (53genes) was sent. It revealed homozygous mutation of TOE1 gene c.480G>C (p.Lys160Asn variant). This gene is extremely rare and very few cases have been reported. Laparoscopy and surgery has been planned.

Discussion: Mutation in TOE1(Target of early growth response gene 1) leads to defects in DNA replication. Other diseases associated with Pontocerebellar Hypoplasia Type 7 and Familial Adenomatous Polyposis 2.Various human phenotypes of TOE1 mutations are seen in both 46XX and 46XY leading to abnormalities of genitalia. Conclusion:. In largely consanguinous married population of Pakistan diverse genetic disorders are quite common. Very rare mutations have also been reported in 46XY DSD. TOE 1 gene has been reported for the first time in 46XY DSD from Pakistan.TOE1 gene should be included in genetic panels of 46 XY and XX DSD.