Mosaic Trisomy 14 with Severe Short Stature: A Case Report.
This case report shows a slight increase in height after rhGH treatment in a child with mosaic trisomy 14, but it does not provide evidence for treatment efficacy or safety.
Where it sits
this study against the rest of the hgh (somatropin) corpusSummary and findings
This case report discusses a 10-year-3-month-old girl with mosaic trisomy 14 presenting with severe short stature and developmental delay. The patient was prescribed recombinant human growth hormone (rhGH) at a dose of 0.22 mg/kg/week. After three months, the patient's height increased by 1.9 cm, but no treatment efficacy or safety conclusions can be drawn from this observation.
Abstract
Mosaic trisomy 14 is a rare chromosomal anomaly with a broad phenotypic spectrum. We report a 10-year-3-month-old girl with severe short stature, developmental delay, and repaired patent ductus arteriosus. An incompletely documented combined insulin-clonidine stimulation test yielded a peak GH concentration of 6.85 ng/mL and was not considered sufficient to establish growth hormone deficiency. Karyotyping of 100 peripheral-blood metaphases showed 47,XX,+14[6]/46,XX[94]. Initial copy-number sequencing detected a 34.37 Mb mosaic 14q gain; repeat SNP-based chromosomal microarray analysis demonstrated an approximately 86.83 Mb 14q11.2-q32.33 mosaic gain at an array-estimated fraction of approximately 50%, compatible with the cytogenetic diagnosis. Targeted 14q32.2 analysis showed increased total and methylated-allele dosage, with methylated fractions of 48.6-62.3%, interpreted as dosage imbalance within the broader 14q gain rather than an independent epimutation. Four STR loci showed biparental inheritance. Quantitative peak-height and peak-area analysis at three informative, bias-correctable STR loci demonstrated excess paternal-allele dosage, providing independent support for, but not definitive proof of, paternal origin of the additional chromosome 14. rhGH was prescribed for SGA with persistent short stature at 0.22 mg/kg/week. At three months, height was 124.7 cm (+1.9 cm); no adverse events were reported. These observations do not establish treatment efficacy or safety.
Background
This paper addresses the clinical implications of mosaic trisomy 14, a rare chromosomal anomaly associated with various phenotypes, including severe short stature. Prior knowledge indicates that growth hormone deficiency can be a concern in short stature cases, but the relationship between chromosomal anomalies and GH levels is not well established. This case report is significant as it explores the potential role of rhGH in a patient with a unique genetic profile.
Methods
This is a case report involving a 10-year-3-month-old girl diagnosed with mosaic trisomy 14. The patient underwent a combined insulin-clonidine stimulation test to assess GH levels, with karyotyping performed on 100 peripheral-blood metaphases. The patient was treated with rhGH at a dosage of 0.22 mg/kg/week for three months, with height as the primary outcome measure.
Results
The peak GH concentration was 6.85 ng/mL, which did not meet the criteria for GH deficiency. After three months of treatment with rhGH, the patient's height increased to 124.7 cm, representing a gain of 1.9 cm. No adverse events were reported during the treatment period.
Interpretation
The findings suggest that while there was a measurable increase in height, the clinical significance of a 1.9 cm increase over three months may be minimal, especially given the lack of a control group. The peak GH level indicates that GH deficiency was not present, raising questions about the appropriateness of treatment in this context. The limitations of a single case report and the absence of definitive proof regarding the paternal origin of the additional chromosome 14 further complicate the interpretation of these results.
Key findings
- Peak GH concentration of 6.85 ng/mL not sufficient to establish growth hormone deficiency.
- Height increased from baseline to 124.7 cm (+1.9 cm) at three months post-treatment.
- No adverse events were reported.
Limitations
- Case report with no control group.
- Observations do not establish treatment efficacy or safety.
- Single patient limits generalizability.
- Short follow-up of three months.