ESPE Abstracts

Background: The Hedgehog (HH) family plays an important role in the development, proliferation and homeostasis in various tissues and organs. Desert hedgehog(DHH), as a member of this family, is mainly involved in the normal development of testis and the formation of nerve sheath. DHH variation mainly causes 46, XY disorders of sex development (DSD) with or without minifascicular neuropathy(MN). Up to date, only 22 affected patients in detail have been reported worldwide. Whether other organs are involved, rarely reported.

Case presentation: We reported a Chinese female carrying a pathogenic variant (c.1027T>C, p. Cys343Arg) in DHH exon 3, the karyotype analysis was 46, XY and SRY gene was positive, which consistent with her phenotype 46, XY DSD with MN. With a female phenotype, she was admitted because of abnormal breast development, lack of menarche and “muscle spasms” occasionally. Slow motor and sensory conduction velocity were observed on electromyography. Surgical exploration revealed a blindly ending vagina, no uterus were found. The pathology of bilateral gonads was dysplastic testis tissue, which consistent with partial gonadal dysplasia(PGD). During our 6-year follow-up, she received estrogen replacement therapy and the breast development progressed without gender dysphoria. However, the MN became more obvious, before and after electromyography showed that sensory and motor conduction velocity was slowed down. In addition, the patient suffered multiple complications such as obesity, fatty liver, hyperinsulinemia and gastric ulcer occurred, which were basically relieved after our comprehensive management.

Conclusion: We report a patient with 46, XY PGD and MN caused by DHH homozygous variant with a 6-year follow-up. For the first time in this type of patient, the comparison of before and after electromyography and the combination of obesity, fatty liver, hyperinsulinemia and gastric ulcer were shown.