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A Novel GNAS Mutation Causing Isolated Infantile Cushing’s Syndrome
- Source :
- Hormone Research in Paediatrics. 92:196-202
- Publication Year :
- 2019
- Publisher :
- S. Karger AG, 2019.
-
Abstract
- Infantile Cushing’s syndrome is potentially found as part of McCune-Albright syndrome (MAS) which is caused by postzygotic somatic mutations of the GNAS gene. MAS is typically characterized by a triad of polyostotic fibrous dysplasia, café-au-lait skin pigmentation, and precocious puberty or other endocrine hyperfunction. Here, we describe a 2-month-old female infant with features of Cushing’s syndrome without café au lait spots, polyostotic fibrous dysplasia, and clinical evidence of other endocrine hyperfunction. Investigations demonstrated adrenocorticotropic hormone-independent Cushing’s syndrome with bilateral adrenal gland enlargement. Whole-exome sequencing of leukocytes identified a de novo heterozygous novel missense mutation (c.521G>A, p.Cys174Tyr) in the GNAS gene. The patient experienced clinical improvement of Cushing’s syndrome during ketoconazole treatment. Her clinical course was complicated by Pneumocystis jiroveci pneumonia. She also had shortened activated partial thromboplastin time indicating a hypercoagulable state and resulting in pulmonary embolism. She eventually manifested gonadotropin-independent precocious puberty at the age of 13 months after ketoco­nazole was discontinued. This patient demonstrated that Cushing syndrome can be the presenting sign of MAS in infancy. A high index of suspicion followed by genetic analysis is essential in order to establish a diagnosis.
- Subjects :
- musculoskeletal diseases
Pathology
medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
030209 endocrinology & metabolism
McCune–Albright syndrome
03 medical and health sciences
Cushing syndrome
0302 clinical medicine
Endocrinology
Café au lait spot
medicine
GNAS complex locus
Precocious puberty
Missense mutation
Polyostotic fibrous dysplasia
030219 obstetrics & reproductive medicine
biology
business.industry
medicine.disease
Pediatrics, Perinatology and Child Health
biology.protein
Ketoconazole
medicine.symptom
business
medicine.drug
Subjects
Details
- ISSN :
- 16632826 and 16632818
- Volume :
- 92
- Database :
- OpenAIRE
- Journal :
- Hormone Research in Paediatrics
- Accession number :
- edsair.doi...........990606d427a388ffc6b1a0cd7b170316