Uniparental Isodisomy of Chromosome 8 in a One-Year-Old Boy: A Rare Case Report
Laboratory Genetics and Genomics
-
Primary Categories:
- Laboratory Genetics
-
Secondary Categories:
- Laboratory Genetics
Introduction
Uniparental disomy (UPD) involves inheriting both copies of a chromosome from one parent, leading to potentially significant clinical consequences. There are two main types of UPD: isodisomy, which is the inheritance of two of the same homologue of a chromosome from one parent, and heterodisomy, which is the inheritance of two different homologues of a chromosome from one parent. In the case of isodisomy, alternating patterns with and without homozygosity resulting from meiotic recombination events are often observed by SNP microarray, with an absence of heterozygosity in the centromeric region. The presence of two completely identical chromosomes, without any stretches displaying heterozygosity, is typically attributed to monosomy rescue where the second chromosome is a replica of the original one. Identifying UPD is crucial as it can uncover recessive disorders, imprinting disorders, and mosaic aneuploidies that may contribute to a patient's phenotype. Accurate detection of UPD can significantly impact genetic counseling, diagnosis, and management of genetic disorders.
Here, we present a rare case of a one-year-old male with chromosome 8 UPD, where SNP microarray analysis revealed homozygosity across the entirety of chromosome 8, indicating complete isodisomy 8. While chromosome 8 UPD has not typically been associated with imprinting disorders, UPD 8 can still have important clinical implications. An autosomal recessive disorder is possible due to the pairing of identical autosomal recessive mutations within the homozygous regions. Given the rarity of UPD, particularly complete isodisomy for chromosome 8, careful interpretation of the results is crucial for providing accurate diagnosis and appropriate management for the patient.
Case Presentation
We describe a one-year-old male who presented to Pediatric Neurology for concerns of motor dysfunction and developmental delays. The patient had an uncomplicated delivery but was noted to have severe plagiocephaly and torticollis. Around 2 to 3 months of age, he began to show signs of motor dysfunction and developmental delays. At the time of presentation, the patient was not crawling and continues to be nonverbal. A physical exam was notable for macrocephaly with frontal bossing, midline forehead erythematous macule, hypertelorism with flattened nasal bridge, left coloboma, recessed chin and crumpled pinnae. MRI was consistent with Chiari I malformation.
Diagnostic Workup
A chromosomal SNP microarray and karyotype analyses were performed on a peripheral blood sample from the patient. A 30 cell G-band analysis demonstrated a normal 46,XY karyotype. Chromosomal SNP microarray analysis identified complete uniparental isodisomy for chromosome 8.
Treatment and Management
The patient continues to receive physical therapy and is continuously evaluated for speech and occupational therapy.
Outcome and Follow-Up
The patient was referred to a clinical geneticist for evaluation and genetic counseling. Molecular testing to evaluate for CHARGE syndrome was recommended.
Discussion
UPD can contribute to disease through aberrant gene expression in chromosomes with imprinted regions or by causing homozygosity for pathogenic variants in recessive genes. The rarity of UPD 8 offers a unique opportunity to investigate the phenotypic impact of uniparental inheritance.
Conclusion
This case provides a rare report of complete uniparental isodisomy for chromosome 8. Documenting this case provides valuable insights for future cases involving UPD 8 and emphasizes the importance of thorough genetic and clinical investigations in patients with atypical developmental presentations.
Uniparental disomy (UPD) involves inheriting both copies of a chromosome from one parent, leading to potentially significant clinical consequences. There are two main types of UPD: isodisomy, which is the inheritance of two of the same homologue of a chromosome from one parent, and heterodisomy, which is the inheritance of two different homologues of a chromosome from one parent. In the case of isodisomy, alternating patterns with and without homozygosity resulting from meiotic recombination events are often observed by SNP microarray, with an absence of heterozygosity in the centromeric region. The presence of two completely identical chromosomes, without any stretches displaying heterozygosity, is typically attributed to monosomy rescue where the second chromosome is a replica of the original one. Identifying UPD is crucial as it can uncover recessive disorders, imprinting disorders, and mosaic aneuploidies that may contribute to a patient's phenotype. Accurate detection of UPD can significantly impact genetic counseling, diagnosis, and management of genetic disorders.
Here, we present a rare case of a one-year-old male with chromosome 8 UPD, where SNP microarray analysis revealed homozygosity across the entirety of chromosome 8, indicating complete isodisomy 8. While chromosome 8 UPD has not typically been associated with imprinting disorders, UPD 8 can still have important clinical implications. An autosomal recessive disorder is possible due to the pairing of identical autosomal recessive mutations within the homozygous regions. Given the rarity of UPD, particularly complete isodisomy for chromosome 8, careful interpretation of the results is crucial for providing accurate diagnosis and appropriate management for the patient.
Case Presentation
We describe a one-year-old male who presented to Pediatric Neurology for concerns of motor dysfunction and developmental delays. The patient had an uncomplicated delivery but was noted to have severe plagiocephaly and torticollis. Around 2 to 3 months of age, he began to show signs of motor dysfunction and developmental delays. At the time of presentation, the patient was not crawling and continues to be nonverbal. A physical exam was notable for macrocephaly with frontal bossing, midline forehead erythematous macule, hypertelorism with flattened nasal bridge, left coloboma, recessed chin and crumpled pinnae. MRI was consistent with Chiari I malformation.
Diagnostic Workup
A chromosomal SNP microarray and karyotype analyses were performed on a peripheral blood sample from the patient. A 30 cell G-band analysis demonstrated a normal 46,XY karyotype. Chromosomal SNP microarray analysis identified complete uniparental isodisomy for chromosome 8.
Treatment and Management
The patient continues to receive physical therapy and is continuously evaluated for speech and occupational therapy.
Outcome and Follow-Up
The patient was referred to a clinical geneticist for evaluation and genetic counseling. Molecular testing to evaluate for CHARGE syndrome was recommended.
Discussion
UPD can contribute to disease through aberrant gene expression in chromosomes with imprinted regions or by causing homozygosity for pathogenic variants in recessive genes. The rarity of UPD 8 offers a unique opportunity to investigate the phenotypic impact of uniparental inheritance.
Conclusion
This case provides a rare report of complete uniparental isodisomy for chromosome 8. Documenting this case provides valuable insights for future cases involving UPD 8 and emphasizes the importance of thorough genetic and clinical investigations in patients with atypical developmental presentations.