ESPE Abstracts

Background: Childhood adrenocortical tumours (ACT) are rare and have well been described as part of familial cancer susceptibility syndromes which are caused by single gene mutations including P53, MEN1, PRKAR1A, CTNNB1 and APC. Adenomas are the most common ACT, but adrenocortical carcinomas (ACC) occur as well. Childhood ACC can be part of the Li-Fraumeni Syndrome and Beckwith-Wiedemann syndrome. ACC can also occur in familial adenomatous polyposis coli (FAP). FAP is a colon cancer predisposition syndrome caused by germline inactivation of the adenomatous polyposis coli tumour-suppressor gene (APC) located on the long arm of chromosome 5 (5q21–5q22). The main feature of FAP is polypogenesis beginning in early adulthood, ACC have been reported only in adult patients.

Case report: We report on a male infant, offspring from non-consanguineous german parents, who presented with clinical signs of Cushing syndrome at the age of 3-months. Additionally the child had unilateral club foot and micropenis. Diagnostic work-up revealed ACTH-independent hypercortisolism due to unilateral adrenocortical tumour. Tumour resection was performed at the age of 4 months, the tumour was classified as adrenocortical carcinoma (T2 N0 M0). Clinical signs of hypercortisolism resolved, but the child’s facial features remained dysmorphic. Poor growth in association with micropenis as well as IGF1 and IGF BP3 levels far below the normal range led to further endocrinological evaluation at the age of 10 months. Severe growth hormone neurosecretory dysfunction was diagnosed. Subsequent growth hormone substitution led to catch-up growth, but the child’s severely retarded psychomotor development and muscle hypotonia remained unaffected. At the age of 12 months comparative genomic hybridization identified a large interstitial deletion of chromosome 5q expanding over a 19.4-Mb region (5q21.3–5q23.3) including the APC gene. Other genes within the deleted region may be responsible for psychomotor retardation und muscle hypotonia.

Conclusion: ACT caused by deletion of the ACC gene may occur even in childhood and infancy. Chromosomal deletions including known cancer susceptibility genes should be suspected in children with ACT and unexplained additional features.