Effect of growth hormone therapy on severe short stature and skeletal deformities in a patient with combined Turner syndrome and Langer mesomelic dysplasia.
BACKGROUND
Homozygous mutation of the short stature homeobox-containing gene, SHOX, results in Langer mesomelic dysplasia (LMD). Our case presented with severe short stature and skeletal deformities with Turner syndrome (TS) and a SHOX gene abnormality due to a downstream allele deletion in her normal X chromosome. Medical literature review did not reveal similar cases that were treated with GH therapy.


METHODS
We present an 11-yr-old with combined TS and LMD with severe short stature and skeletal deformities. She was studied for the effect of GH therapy on stature and skeletal deformities. Karyotype testing showed 45,X/46,X,idic(X). Genetic analysis of SHOX gene testing did not detect any exonic mutations. Interestingly, both alleles of the flanking marker DXYS233, a marker downstream of the 3' end of SHOX coding sequence, were absent with resultant LMD. GH therapy in the mean dose of 0.321 mg/kg/wk was administered for 4 yr (0.287, 0.355, 0.317, and 0.327 mg/kg/week in the first, second, third, and fourth years, respectively). Clinical data were reviewed.


RESULTS
The growth rates of 3.46, 3.87, 2.3, and 0.7 cm/yr were observed in the first, second, third, and fourth years of the GH therapy, respectively. There was no clinical deterioration of the skeletal deformities.


CONCLUSIONS
There was a failure to achieve growth improvements with GH therapy for 4 years, but there was no worsening of the skeletal deformities. We conclude that GH therapy may not be beneficial in severe short stature due to combined TS and LMD resulting from homozygous SHOX deficiency.
Department of Pediatric Endocrinology, New York University Medical Center, 550 First Avenue, New York, New York 10016, USA. bina.shah@nyumc.org
Bina C
BC
Shah
Ellen S
ES
Moran
Andrew R
AR
Zinn
John G
JG
Pappas
D001827:Body Height / Q000187:drug effects*; D001842:Bone and Bones / Q000002:abnormalities*; D002648:Child; D020732:Cytogenetic Analysis; D005260:Female; D005819:Genetic Markers; D006128:Growth / Q000187:drug effects / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics; D019382:Human Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D015826:Langer-Giedion Syndrome / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D011994:Recombinant Proteins / Q000627:therapeutic use; D000074122:Short Stature Homeobox Protein; D014424:Turner Syndrome / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology
D005819:Genetic Markers; D018398:Homeodomain Proteins; D011994:Recombinant Proteins; C106071:SHOX protein, human; D000074122:Short Stature Homeobox Protein; D019382:Human Growth Hormone