A strange picture of karyotype and good response to higher dosage of GH

Introduction: Genes on Xp chromosome are central for stature. In Turner Syndrome and SHOX mutation GH therapy should generally begin as soon as growth failure occurs and for a good reaction higher doses are required. Monosomy X is found in about 45% of patient with Turner syndrome; in the remaining patients is found structural chromosome abnormality or mosaicism. The phenotype of TS is extraordinarily broad. Individuals with a 45,X tend to have a more severe phenotype than those who are mosaic with a normal cell line (45,X/46,XX or 45,X/46,XY). However, there is no predictable phenotype-genotype correlation. Case report: We report a 4 years old girl with growth failure: she was small for gestational age (SGA) : BW -2SDS, height -2/-3SDS with a Mid Parent Height +1/+2SDS; she has been treated with GH therapy (0.2 mg/kg/week). As we noted no growth improvement, we performed a chromosome analysis, discovering a picture of Turner-like Syndrome:46 X,Xqter ->Xp22.3->Xq13->Xqter karyotype. So we increased GH therapy(0.3 mg/kg/week) and statural growth passed from -2,5 to M SDS (+ 2,5 Delta SDS). To explain the surprising growth enhancement we performed FISH analysis with specific probe for centromere and subtelomeric regions of X chromosome long arm (Xq) and short arm (Xp) and MLPA analysis for subtelomeric region in particular SHOX gene. We found two centromeres and a partial duplication of Xq and there was no SHOX gene deficit. Conclusion: We are going to perform other genetic analyses (such as array-CGH) for the understanding of the low stature and of the very good answer to GH therapy and besides we must remember that sometimes phenotype of duplication syndromes is similar to the deletion ones