A Chinese Case of X-Linked Acrogigantism and Systematic Review

Abstract

Introduction: To describe a Chinese case of X-linked acrogigantism (X-LAG) and summarize the characteristics and treatment of all reported cases. Methods: Clinical materials and biological samples from a 5-year and 2-month-old female due to “growth acceleration for 4 years” were collected. Array comparative genomic hybrid (aCGH) and further verification were performed. All X-LAG cases from the PubMed and Web of Science databases were collected and summarized using available data. Results: The patient presented accelerating growth since 1 year of age, and her height reached 134.6 cm (+5.24 standard deviation score, SDS) when she was 5 years and 2 months old. She also had coarsening facial features, snoring, and acral enlargement. Growth hormone (GH) was not suppressed by the glucose-GH inhibition test, and insulin-like growth factor 1 (IGF-1) and prolactin levels were elevated. Pituitary magnetic resonance imaging (MRI) revealed a pituitary enlargement with a maximum diameter of 22.3 mm. Octreotide imaging indicated the presence of a pituitary adenoma. The tumor shrank slightly after three courses of somatostatin analog but without clinical or biochemical remissions, of which the GH nadir value was 9.4 ng/ml, and IGF-1 was elevated to 749 ng/ml. Therefore, she underwent transsphenoidal surgery. Immunohistochemistry showed GH-positive and PRL-positive cells in the pituitary adenoma. Xq26.3 microduplication of the patient’s germline DNA was identified by aCGH. Of all 35 reported cases, females accounted for 71.43%. There were 93.10% and 53.83% patients with hyperprolactinemia and hyperinsulinemia, respectively. Pathology showed that 75.00% of cases were adenomas. Ninety percent of cases had germline variants. The clinical and biochemical remission rates were 78.26% and 82.61%, respectively. However, the rate of complication occurrence during therapy reached 80%. Conclusion: It is important to recognize the possibility of X-LAG when a child under 2 years old presents overgrowth. Early diagnosis and treatment are of great importance for better treatment efficacy and clinical outcome.

Case report: Management of pediatric gigantism caused by the TADopathy, X-linked acrogigantism

“…The current study describes the complicated treatment journey that can occur in patients with the earliestonset form of somatotropinomas, X-LAG. X-LAG is a very rare disease with fewer than 50 cases having been described in the decade since it was first identified as a distinct entity (2,5,6,8,10,(17)(18)(19)(20)(25)(26)(27)(28)(29). The current patient illustrates well many of the characteristic features of X-LAG, namely, sporadic onset in a previously normally-growing female infant, with the first signs of overgrowth occurring around the first birthday.…”

Genetics of Acromegaly and Gigantism

“…Overview : XLAG is a recently described disease caused by either germline or somatic duplications of the GRP101 gene [ 32 ]. The prevalence of XLAG varies between 7.8–10% of gigantism patients with female predominance (2/3 of the cases) [ 16 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 ]. To date, less than 40 cases of XLAG have been described.…”

“…Fasting hyperinsulinemia has been noted in 1/3 of cases, and 20% of patients had acanthosis nigricans. Less frequently, sleep apnoea, extensive perspiration or abdominal distension have been observed [ 16 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 ].…”