Acromegaloidism with normal growth hormone secretion associated with X-Tetrasomy

Abstract

We reported a case of a 26-year-old female who was referred to our clinic with the diagnosis of possible acromegaly. She was born from a term pregnancy by forceps delivery. The patient was diagnosed as having hip luxation at one month and spoke her first word at 15 months. She had been diagnosed at the age of 9 years old as having perinatal encephalopathy with intellectual and motor affectation. Since this period of time she has undergone an insidious change in her appearance, mainly comprising progressive coarsening of the face. For this reason she was submitted to our clinic with presumed acromegaly. Dynamic tests of growth hormone secretion ruled out such a diagnosis. The Patient was considered as having "acromegaloidism", a term used for patients whom manifest clinical features of acromegaly but do not present a demonstrable growth hormone hypersecretion. Subsequently cytogenetic evaluation revealed an infrequent chromosome pattern: X-Tetrasomy. In the present article a differential diagnosis of acromegaloidism and the potential role of genes present on X-chromosome involved in human growth such as SHOX gene are discussed. Overdosification of SHOX gene might explain tall stature of girls with X-tetrasomy. Our observation suggested that X-tetrasomy should be considered in the differential diagnosis of acromegaloidism. Furthermore, this may lead to the identification of new genes in the X-chromosome that are important for growth of facial structures.

The Klinefelter syndrome is associated with high recurrence of copy number variations on the X chromosome with a potential role in the clinical phenotype

“…In contrast, the occurrence of SHOX duplications is apparently rare, with only few cases reported so far (Grigelioniene et al ., ; Tachdjian et al ., ; Roos et al ., ; Thomas et al ., ; D'Haene et al ., ; Gervasini et al ., ) and no direct relationship with any specific phenotype has yet been defined, also because it has been reported in association with normal to tall stature (Ogata et al ., ; Adamson et al ., ). Short stature in Turner's syndrome is caused by haploinsufficiency of SHOX , whereas an effect of SHOX overdosage was reported in females with supernumerary X chromosomes (Adamson et al ., ; Kanaka‐Gantenbein et al ., ; Alvarez‐Vázquez et al ., ; Nishi et al ., ) Consequently, the tall stature in KS may not be only due to hypogonadism, but may well be caused by excessive expression of SHOX .…”

Growth in children – a fascinating story

“…Point mutations have been found in only 3.2% of patients with idiopathic short stature [2]. Over expression of SHOX-genes as in females with triple-X syndrome or in boys with Klinefelter syndrome is involved in tall stature [3]. In other forms of chromosomal imbalance (for instance in Down-syndrome) the over dosage of genes, located outside the D21S55 region, is followed by short stature [4].…”