@article {113,
	title = {Aggressive tumor growth and clinical evolution in a patient with X-linked acro-gigantism syndrome.},
	journal = {Endocrine},
	volume = {51},
	year = {2016},
	month = {2016 Feb},
	pages = {236-44},
	abstract = {<p>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 {\texttimes} 23.9 {\texttimes} 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 {\texttimes} 58.1 {\texttimes} 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.</p>},
	keywords = {Adenoma, Child, Genetic Diseases, X-Linked, Gigantism, Humans, Male, Pituitary Neoplasms, Treatment Outcome},
	issn = {1559-0100},
	doi = {10.1007/s12020-015-0804-6},
	author = {Naves, Luciana A and Daly, Adrian F and Dias, Luiz Augusto and Yuan, Bo and Zakir, Juliano Coelho Oliveira and Barra, Gustavo Barcellos and Palmeira, Leonor and Villa, Chiara and Trivellin, Giampaolo and J{\'u}nior, Armindo Jreige and Neto, Flor{\^e}ncio Figueiredo Cavalcante and Liu, Pengfei and Pellegata, Natalia S and Stratakis, Constantine A and Lupski, James R and Beckers, Albert}
}
@article {76,
	title = {Somatic mosaicism underlies X-linked acrogigantism syndrome in sporadic male subjects.},
	journal = {Endocr Relat Cancer},
	volume = {23},
	year = {2016},
	month = {2016 04},
	pages = {221-33},
	abstract = {<p>Somatic mosaicism has been implicated as a causative mechanism in a number of genetic and genomic disorders. X-linked acrogigantism (XLAG) syndrome is a recently characterized genomic form of pediatric gigantism due to aggressive pituitary tumors that is caused by submicroscopic chromosome Xq26.3 duplications that include GPR101 We studied XLAG syndrome patients (n= 18) to determine if somatic mosaicism contributed to the genomic pathophysiology. Eighteen subjects with XLAG syndrome caused by Xq26.3 duplications were identified using high-definition array comparative genomic hybridization (HD-aCGH). We noted that males with XLAG had a decreased log2ratio (LR) compared with expected values, suggesting potential mosaicism, whereas females showed no such decrease. Compared with familial male XLAG cases, sporadic males had more marked evidence for mosaicism, with levels of Xq26.3 duplication between 16.1 and 53.8\%. These characteristics were replicated using a novel, personalized breakpoint junction-specific quantification droplet digital polymerase chain reaction (ddPCR) technique. Using a separate ddPCR technique, we studied the feasibility of identifying XLAG syndrome cases in a distinct patient population of 64 unrelated subjects with acromegaly/gigantism, and identified one female gigantism patient who had had increased copy number variation (CNV) threshold for GPR101 that was subsequently diagnosed as having XLAG syndrome on HD-aCGH. Employing a combination of HD-aCGH and novel ddPCR approaches, we have demonstrated, for the first time, that XLAG syndrome can be caused by variable degrees of somatic mosaicism for duplications at chromosome Xq26.3. Somatic mosaicism was shown to occur in sporadic males but not in females with XLAG syndrome, although the clinical characteristics of the disease were similarly severe in both sexes.</p>},
	keywords = {Adult, Female, Genetic Diseases, X-Linked, Gigantism, Humans, Male, Middle Aged, Mosaicism, Polymerase Chain Reaction, Syndrome, Young Adult},
	issn = {1479-6821},
	doi = {10.1530/ERC-16-0082},
	author = {Daly, Adrian F and Yuan, Bo and Fina, Frederic and Caberg, Jean-Hubert and Trivellin, Giampaolo and Rostomyan, Liliya and de Herder, Wouter W and Naves, Luciana A and Metzger, Daniel and Cuny, Thomas and Rabl, Wolfgang and Shah, Nalini and Jaffrain-Rea, Marie-Lise and Zatelli, Maria Chiara and Faucz, Fabio R and Castermans, Emilie and Nanni-Metellus, Isabelle and Lodish, Maya and Muhammad, Ammar and Palmeira, Leonor and Potorac, Iulia and Mantovani, Giovanna and Neggers, Sebastian J and Klein, Marc and Barlier, Anne and Liu, Pengfei and Ouafik, L{\textquoteright}Houcine and Bours, Vincent and Lupski, James R and Stratakis, Constantine A and Beckers, Albert}
}
