Congenital Neuroblastoma in the Presence of Classical Congenital Adrenal Hyperplasia (CAH) Associated with a Novel Mutation

Presentation Number: SAT 361
Date of Presentation: April 1st, 2017

Pedro Pagán Banchs*, Selma Feldman Witchel, Amr Morsi and A. Kim Ritchey
Childrens Hospital of Pittsburgh of UPMC, Pittsburgh, PA


Background: Co-existing congenital neuroblastoma (NB) and classical CAH are extremely rare. To our knowledge, this patient is the first to have been identified prenatally.

Case: A 7-day old baby boy (BW 3.49 kg), infant of diabetic mother treated with diet, was found to have possible cystic kidneys on prenatal ultrasound (U/S). Physical exam revealed no focal abnormalities and normal male genitalia with bilateral palpable testes. A postnatal U/S showed an enlarged left adrenal gland without focal mass, a right adrenal mass (2.9 x 3.3 x 4 cm), normal appearing kidneys, and possible UPJ obstruction. His 17-OHP newborn screen was elevated at 229 ng/mL (extracted value, 68 ng/ml). Diagnostic studies showed elevated 17-OHP, 14,800 ng/dL (80-420 ng/dl) and elevated plasma renin activity 159.59 ng/ml/h (0.25-5.82)] confirming the diagnosis of CAH due to 21-hydroxylase deficiency. Additional studies showed elevated urinary homovanillic acid (HVA) and vanillylmandelic acid (VMA) consistent with the diagnosis of congenital neuroblastoma.

After confirmation of the CAH diagnosis, hydrocortisone and fludrocortisone replacement therapies were initiated. Subsequent MRI and MIBG scans were consistent with the diagnosis of neuroblastoma. Serial adrenal imaging has shown continued decrease in the size of the adrenal mass (now 2.3 x 2.2 x 2.0 cm). HVA and VMA excretion have decreased.

Genetic analyses showed normal male 46,XY karyotype. Genetic mutation analysis of CYP21A2 revealed two mutations, an intron 2G splicing mutation (c.293-13A/C>G) and a novel mutation, T>C at nucleotide c.527 in exon 4, which is predicted to generate a missense mutation, p.L175P. Based on bioinformatics tools, p.L175P is predicted to be deleterious. Amino acid alignment with other mammalian CYP21A2 genes indicates that this is a highly conserved amino acid (1).

Conclusion: CAH was diagnosed prior to neuroblastoma among the previously reported patients with concurrent CAH and neuroblastoma (2,3). The natural history of congenital NB is typically spontaneous resolution. The NB in our patient was likely detected because of the prenatal U/S findings and diagnosis of CAH. A novel CYP21A2 mutation was identified in our patient. Although the adrenal vein provides cortisol to the adrenal medulla, likely no causal relationship exists between CAH and NB. Rather the NB represents an incidental finding in a patient with CAH.


Nothing to Disclose: PP, SFW, AM, AKR