Endocrine Abstracts

Introduction: Primary Osteoma Cutis is associated with Albrights Hereditary osteodystrophy (AHO) due to inactivating GNAS mutation. It is inherited in an autosomal dominant or sporadic manner. Phenotype in GNAS mutation is varied due to parent specific gene expression. Maternally inherited GNAS mutation leads to hormone resistance, but paternally inherited mutation leads to AHO features without hormone resistance. Medulloblastoma is the most common malignant brain tumour in childhood. There is a rare association with germline mutations in GNAS causing medulloblastoma. We report a case with this rare combination.

Case History: A 2-year-old boy presented with multiple small discrete plaque like lesions in the skin his trunk and limbs. He was born at 37 weeks without any antenatal or postnatal complication except for neonatal jaundice. He was noted to have fleshy plaque like lesions under the skin over his abdomen during the neonatal period which spread to other areas over time. Skin biopsy of the lesion revealed osteoma cutis which prompted the genetic testing. He was diagnosed with heterozygous mutation in GNAS. His biochemical investigation didn’t reveal any hormone resistance. He had mild developmental delay. He also had a non-traumatic right fibula fracture at 1.5 years which healed subsequently and seems unrelated to his underlying condition. He had a normal Bone health index (BHI) of 3.9 (+0.8 SDS). He presented at the age of 2.5 years with unsteady gait, lethargy, divergent squint and vomiting with cerebellar signs. MRI brain revealed a posterior fossa tumour without evidence of metastatic spread. He underwent complete surgical resection. Histology revealed desmoplastic nodular medulloblastoma, SHH molecular group. He received chemotherapy according to the HIT-SKK protocol. Tumour next generation sequencing was normal, including MYCN, MYC, CTNNB1 and TP53. Whole genome sequencing of the tumour confirmed GNAS mutation.

Discussion: Somatic GNAS mutation has been identified in several tumours including medulloblastoma. Germline inactivating GNAS mutation have been rarely identified in SHH activated medulloblastoma group in the recent years. Reduced expression in GNAS in tumour tissues lead to poorer prognosis. This case highlights the importance of vigilantly looking for medulloblastoma when children with underlying germline GNAS mutation present with neurological symptoms.