Denys-Drash Sydrome (DDS) is a rare condition of renal and gonadal dysgenesis. Typically diagnosed in early childhood, it is associated with end stage kidney disease, intersex disorders with risk of gonadoblastoma; and Wilms’ tumour. We report a case involving a delayed diagnosis of DDS in a 23 year old woman with severe CKD-MBD and delayed puberty.
The patient had a history of congenital renal dysplasia. She had required peritoneal dialysis from age eight months, live renal transplant at age three years and haemodialysis since graft failure at age 20 years. The CKD-MBD involved severe secondary hyperparathyroidism (PTH 172pmol/L, corrected serum calcium 1.84-2.17mmol/L, ALP 1200UL) and rapidly evolving osteomalacia with debilitating skeletal deformities. She was also found to have primary amenorrhoea, characterised by hypergonadotrophic hypogonadism, absent thelarche, a hypoplastic rudimentary uterus on pelvic imaging, and a karyotype of 46,XY. Genetic testing for DDS with Wilm’s tumour-1 (WT-1) suppressor gene mutation is still pending. Management has been multi-disciplinary. To attenuate her secondary hyperparathyroidism and osteomalacia, phosphate binders and calcitriol doses have been increased. Puberty induction has also been commenced with topical estradiol 25mcg/24hr. Dysmorphic gonadal tissue will need resection if found on laparoscopic exploration to mitigate gonadoblastoma risk. The long-term plan is for a second renal transplant.
This case is an important reminder that while disorders of pubertal development are commonly associated with CKD in adolescent patients, puberty should not be absent. As such, primary amenorrhoea warrants thorough investigation. The consequences of the delay in diagnosis of gonadal dysgenesis are significant for this patient: the hypogonadism is likely to have potentiated the bone loss associated with her CKD-MBD which has resulted in debilitating skeletal deformities; and her renal transplant has had to be deferred until the DDS is sufficiently optimised.