Denys-Drash syndrome with cerebral atrophy and neurological deficit - a case report

Abstract

We present a case of Denys-Drash syndrome complicated by cerebral atrophy and severe neurological deficit, not traditionally associated with the syndrome. Patient presented as a female infant, born at 37 weeks gestation. Immediately after birth a low amount of urine was noted, as well as a reduced muscle tone. Neurosonography revealed slight hydrocephalus with no clinical signs of compression. She was discharged home, and presented at our tertiary centre at one month of age with severe generalised edema, hypertension, and anuria. Neurosonography was normal at this time. Peritoneal dialysis was initiated. Karyotype testing showed 46, XY. An oncogene panel revealed a pathogenic heterozygous variant of WT1 (NM_024426.6(WT1):c. [1316G>A];[1316=]), confirming Denys-Drash syndrome. Abdominal and pelvic MRI showed no signs of nephroblastoma, and no gonadal tissue was identified. At two months of age, due to anuric ESRD and risk of malignancy, a double nephrectomy was performed. Nephrogenic foci were found in the histopathological study. Poor wound healing was noted, resulting in hernia at the incision site. In the following weeks the patient was increasingly irritable, had had worsening dysphagia. At 3 months focal seizures started to occur. Neurosonography and MRI showed severe cerebral atrophy, showing radiological signs of hypoglycaemic origin, however no hypoglycaemia episodes were registered. Full exome sequencing and metabolic testing revealed no additional inherited abnormalities. At 6 months of age, due to progressive swallowing dificulties a gastrostomy was placed, again showing poor postoperative wound healing, which resulted in peritonitis one week after surgery. The healing process took 1 month, during which time parenteral feeding was utilised. At 18 months of age the patient remains seizure-free with minimal doses of levetiracetam and phenobarbital, however MRI shows progressive cerebral atrophy, including atrophy of the optic nerves, resulting in blindness. Psychomotor development remains severely delayed. The cerebral atrophy and neurological defcit were initially attributed to post-nephrectomy hypotension, however the patient’s condition continued to deteriorate later in life with blood pressure well under control. Also, the patient did show some signs of neurological defcit (low muscle tone, dysphagia) before the nephrectomy was performed. The exact cause of the deficit remains unexplained at this time.