SAT-463 Familial X-Linked Acrogigantism: Postnatal Outcomes and Tumor Pathology in a Prenatally Diagnosed Infant and His Affected Mother

Abstract

Background: X-linked acrogigantism (X-LAG), a condition of infant-onset acrogigantism marked by elevated levels of GH, IGF-1, and PRL, is extremely rare with 33 cases reported in the literature (1), including 7 total familial cases from 3 kindreds. Clinical Case: The patient’s mother, diagnosed with acrogigantism at 21 months of age, underwent pituitary tumor excision at 24 months with the expected subsequent hypopituitarism, diabetes insipidus, and seizure disorder. For over 30 years, stable GH, IGF-1, and PRL levels and serial MRI studies indicated no tumor recurrence. On pre-conception planning genetic studies, X-LAG was diagnosed: SNP microarray showed Xq26.3 microduplication. After conception at age 32, CVS with SNP microarray showed the same microduplication, confirming familial X-LAG in the male fetus (2,3). The infant experienced rapid interval growth between 5-6 months of age in conjunction with rising GH, IGF-1, and PRL levels and enlarging suprasellar pituitary mass, which continued to grow despite titration of bromocriptine started at 6 months. He underwent pituitary tumor resection at 15 months with development of the expected hypopituitarism requiring hormone replacement therapies. The pituitary adenoma resembles the mother’s pituitary adenoma, with tumor cells arranged in trabeculae and glandular structures. Many tumor cells in both cases express GH, PRL and Pit-1. The expression of other lineage-specific transcription factors (T-PIT, SF1) and Sox2 demonstrates the multipotentiality of X-LAG tumors, an observation not previously described. Both tumors showed an elevated Ki-67 proliferation index—5.6% (mother) and 8.5% (patient)—the highest reported in X-LAG (most are < 3%) (1). GH, IGF-1, and PRL levels fell precipitously and growth acceleration decreased, with WHO height Z-score decrease from 2.6 to 1.9 by 20 months of age. Conclusion: This is the first prenatally-diagnosed case of X-LAG. Prospective follow-up with close clinical evaluation provides insight into the natural history of X-LAG. Utilization of cell lineage-specific transcription factors and stem cell markers reveals unexpected complexity of X-LAG tumors.