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Short-limb dwarfism and hypertrophic cardiomyopathy in a patient with paternal isodisomy 14: 45,XY,idic(14)(p11)
C A Walter1, L G Shaffer, C I Kaye
1Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio 78284-7762, USA.
Insights
This study details a rare case of paternal uniparental disomy of chromosome 14 (UPD14) in an infant. The findings highlight UPD14
Area of Science:
- Genetics
- Developmental Biology
- Pediatrics
Background:
- Uniparental disomy (UPD) can cause disorders through imprinting or homozygous mutations.
- Paternal UPD14 is a rare genetic condition with complex clinical manifestations.
Purpose of the Study:
- To report a case of paternal UPD14 in an infant.
- To describe the prenatal and postnatal findings associated with this condition.
- To elucidate the genetic and cytogenetic basis of the disorder.
Main Methods:
- Prenatal ultrasound evaluation at 30 weeks gestation.
- Postnatal physical examination and anthropometric measurements.
- Cytogenetic analysis including karyotyping, C-banding, and fluorescence in situ hybridization (FISH).
- DNA analysis to determine uniparental disomy.
Main Results:
- Prenatal ultrasound revealed polyhydramnios, short limbs, abnormal hand position, small thorax, and absent fetal stomach.
- Postnatal findings included low birth weight, short stature, contractures, and a small thorax with upslanting ribs.
- Cytogenetic studies identified a de novo dicentric Robertsonian translocation of chromosome 14 (idic(14)(p11)).
- DNA analysis confirmed paternal uniparental isodisomy for chromosome 14.
Conclusions:
- Paternal UPD14, associated with a dicentric chromosome 14, can lead to severe developmental abnormalities.
- This case underscores the importance of comprehensive genetic and cytogenetic evaluation in diagnosing UPD.
- Early identification and management, including supportive care for conditions like hypertrophic cardiomyopathy, are crucial.
Abstract:
Uniparental disomy (UPD) has been shown to result in specific disorders either due to imprinting and/or homozygosity of mutant alleles. Here we present the findings in a child with paternal UPD14. Ultrasound evaluation was performed at 30 weeks of gestation because of abnormally large uterine size. Pertinent ultrasound findings included polyhydramnios, short limbs, abnormal position of hands, small thorax, and nonvisualization of the fetal stomach. Post-natally the infant was found to have a low birth weight, short birth length, contractures, short limbs, and a small thorax with upslanting ribs. Assisted ventilation and gastrostomy were required. At age 6 months, the infant required hospitalization for hypertrophic cardiomyopathy which responded to Atenolol. Initial cytogenetic studies demonstrated an apparently balanced de novo Robertsonian translocation involving chromosomes 14 and a karyotype designation of 45,XY,t(14q14q). No indication of mosaicism for trisomy 14 was observed in metaphase spreads prepared from peripheral blood lymphocytes or skin-derived fibroblasts. C-band and fluorescence in situ hybridization results demonstrated that the chromosome was dicentric. DNA analyses showed paternal uniparental isodisomy for chromosome 14. Based on the cytogenetic and DNA results a final karyotype designation of 45,XY,idic(14)(p11) was assigned to this infant with paternal isodisomy of chromosome 14.