ESPE Abstracts

Background: X-chromosome monosomy is the most common sex abnormality in females, with a higher prevalence of cancer than the general population. Virilizing adrenocortical tumors are rarely seen in patients with Turner’s Syndrome. There have been 2 reported cases of simultaneous TP53 mutations (Li Fraumeni’s syndrome) and Turner’s syndrome. Here we report first case with this rare association from Kuwait.

Clinical Case: A six-month-old girl brought by her grandmother with aggressive behavior, virilization, and pubic hair of unknown duration since grandmother just took care of the child after the recent loss of the mother because of leukemia. The examination was limited because the patient was agitated and aggressive. The examination revealed an increased growth with length >95th percentile, weight was 75th percentile, and pubic hair tanner stage II-III. Genital exam showed clitoromegaly of 4 cm, no labioscrotal fusion, and no palpable gonads. Total testosterone was 9.73 nmol/L, FSH level was 2.28 IU/L, and LH was 0.86 IU/L. Blood glucose and electrolytes were within normal. The ACTH stimulation test: peak cortisol was 544 nmol/L, and peak 17-hydroxyprogesterone was 25.23 nmol/L. Advanced bone age 2-2.5 years. US abdomen reported a normal sized uterus and vagina with no visualized gonads, and a large abnormal configuration of the left kidney. MRI confirmed the previously reported left suprarenal soft tissue tumor measuring 5.2x5.8x6 cm, which was heterogenous, highly vascular, compressing the upper pole of the left kidney with a clear line of cleavage. Karyotype revealed 45 XO, Turner syndrome with negative SRY gene. PET-scan excluded metastasis. Urine levels of epinephrine, norepinephrine, dopamine, vanillyl mandelic acid (VMA), and homovanillic acid (HVA) were within normal range. Left adrenalectomy was done and histopathology report showed adrenal cortical carcinoma, oncocytic type. Targeted Inherited Cancer panel sequencing on DNA extracted from peripheral blood revealed a heterozygous pathogenic variant in TP53: c.374C>G (p.Thr125Arg) which is associated with Li-Fraumeni syndrome.

Conclusion: This is the third case of Li Fraumeni’s Syndrome linked to X-monosomy, raising the question of the correlation between the two syndromes, and highlighting the uncommon occurrence of adrenocortical cancers in Turner’s Syndrome.