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Aggressive tumor growth and clinical evolution in a patient with X-linked acro-gigantism syndrome

  • Endocrine Genetics/Epigenetics
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Abstract

X-linked acro-gigantism (X-LAG) syndrome is a newly described disease caused by microduplications on chromosome Xq26.3 leading to copy number gain of GPR101. We describe the clinical progress of a sporadic male X-LAG syndrome patient with an Xq26.3 microduplication, highlighting the aggressive natural history of pituitary tumor growth in the absence of treatment. The patient first presented elsewhere aged 5 years 8 months with a history of excessive growth for >2 years. His height was 163 cm, his weight was 36 kg, and he had markedly elevated GH and IGF-1. MRI showed a non-invasive sellar mass measuring 32.5 × 23.9 × 29.1 mm. Treatment was declined and the family was lost to follow-up. At the age of 10 years and 7 months, he presented again with headaches, seizures, and visual disturbance. His height had increased to 197 cm. MRI showed an invasive mass measuring 56.2 × 58.1 × 45.0 mm, with compression of optic chiasma, bilateral cavernous sinus invasion, and hydrocephalus. His thyrotrope, corticotrope, and gonadotrope axes were deficient. Surgery, somatostatin analogs, and cabergoline did not control vertical growth and pegvisomant was added, although vertical growth continues (currently 207 cm at 11 years 7 months of age). X-LAG syndrome is a new genomic disorder in which early-onset pituitary tumorigenesis can lead to marked overgrowth and gigantism. This case illustrates the aggressive nature of tumor evolution and the challenging clinical management in X-LAG syndrome.

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Acknowledgments

We thank Núcleo de Apoio a Pesquisa and Instituto Sabin in Brasilia-Brazil, for sample preparations and for performing hormonal studies; Drs. Luiz Augusto Casulari and Dr. Roberpaulo Barboza Filho, for clinical assistance; Ms Doralice Rabello from Pathology Department of University of Brasilia, for preparing tissue samples; Prof Jean Francois Bonneville for discussions on the neuroradiological findings; Dr. Misu Lee for discussion and analysis of somatostatin receptor studies. We thank the CNPq for support. This study was assisted in part by a grant from Fonds d’Investissement de Recherche Scientifique (FIRS) of the Centre Hospitalier Universitaire de Liège to Prof. Albert Beckers. This work was supported in part by grants from the US National Institute of Neurological Disorders and Stroke (NINDS; R01NS058529) to JRL and National Human Genome Research Institute (NHGRI)/National Heart Lung and Blood Institute (NHLBI) (U54 HG006542) to the Baylor-Hopkins Center for Mendelian Genomics.

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Authors and Affiliations

  1. Department of Endocrinology, Faculty of Medicine, University of Brasilia, Brasília, Brazil

    Luciana A. Naves, Juliano Coelho Oliveira Zakir & Armindo Jreige Júnior

  2. Department of Pathology, Faculty of Medicine, University of Brasilia, Brasília, Brazil

    Florêncio Figueiredo Cavalcante Neto

  3. Departments of Endocrinology, Centre Hospitalier Universitaire de Liège, University of Liège, Domaine Universitaire du Sart-Tilman, 4000, Liège, Belgium

    Adrian F. Daly, Leonor Palmeira, Chiara Villa & Albert Beckers

  4. Laboratorio Sabin de Análises Clínicas Brasilia, Brasília, Brazil

    Gustavo Barcellos Barra

  5. Department of Pathology, Hopital Foch, Suresnes Cedex, France

    Chiara Villa

  6. Helmholtz Zentrum Munchen, Institute of Pathology, Neuherberg, Germany

    Natalia S. Pellegata

  7. Departments of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA

    Bo Yuan, Pengfei Liu & James R. Lupski

  8. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA

    James R. Lupski

  9. Department of Neurosurgery, Federal District Base Hospital, Brasília, Brazil

    Luiz Augusto Dias

  10. Section on Endocrinology and Genetics, Program on Developmental Endocrinology & Genetics & Pediatric Endocrinology Inter-Institute Training Program, Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health (NIH), Bethesda, MD, 20892, USA

    Giampaolo Trivellin & Constantine A. Stratakis

  11. Texas Children’s Hospital, Houston, TX, USA

    James R. Lupski

  12. Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA

    James R. Lupski

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  1. Luciana A. Naves
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  2. Adrian F. Daly
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  4. Bo Yuan
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  9. Giampaolo Trivellin
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  12. Pengfei Liu
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  13. Natalia S. Pellegata
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  14. Constantine A. Stratakis
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  15. James R. Lupski
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  16. Albert Beckers
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Correspondence to Albert Beckers.

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Naves, L.A., Daly, A.F., Dias, L.A. et al. Aggressive tumor growth and clinical evolution in a patient with X-linked acro-gigantism syndrome. Endocrine 51, 236–244 (2016). https://doi.org/10.1007/s12020-015-0804-6

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