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A Novel GNAS Mutation Causing Isolated Infantile Cushing's Syndrome
Prapai Dejkhamron1, Chupong Ittiwut2,3, Hataitip TangNgam4
1Department of Pediatrics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.
Hormone Research in Paediatrics
|July 31, 2019
Summary
Cushing syndrome in infants can be an early sign of McCune-Albright syndrome (MAS), a condition caused by GNAS gene mutations. Early genetic testing is crucial for diagnosing MAS presenting with infantile Cushing syndrome.
Area of Science:
- Pediatric Endocrinology
- Genetics
- Endocrinology
Background:
- McCune-Albright syndrome (MAS) is a genetic disorder caused by postzygotic mutations in the GNAS gene.
- MAS classically presents with polyostotic fibrous dysplasia, café-au-lait spots, and endocrine hyperfunction, including precocious puberty.
Observation:
- A 2-month-old infant presented with Cushing syndrome, lacking typical MAS features like café-au-lait spots or fibrous dysplasia.
- Diagnostic evaluation revealed adrenocorticotropic hormone-independent Cushing syndrome with bilateral adrenal gland enlargement.
Findings:
- Whole-exome sequencing identified a novel de novo heterozygous missense mutation (c.521G>A, p.Cys174Tyr) in the GNAS gene.
- The patient showed initial clinical improvement with ketoconazole but later developed complications including Pneumocystis jiroveci pneumonia and pulmonary embolism.
- Gonadotropin-independent precocious puberty manifested after ketoconazole discontinuation, indicating a complex clinical course.
Implications:
- This case highlights that Cushing syndrome can be the initial presentation of MAS in infancy.
- A high index of suspicion and prompt genetic analysis are essential for diagnosing MAS in infants presenting with atypical features.
- Understanding GNAS mutations is critical for managing MAS and its diverse endocrine manifestations in early childhood.