TY - JOUR
T1 - Coexistence of an unbalanced chromosomal rearrangement and spinal muscular atrophy in an infant with multiple congenital anomalies
AU - Ben-Shachar, Shay
AU - Bidwa, Bhattacharjee M.
AU - Potocki, Lorraine
AU - Lalani, Seema R.
PY - 2009/3
Y1 - 2009/3
N2 - Unbalanced chromosomal abnormalities are frequent and account for about 10% of all chromosomal abnormalities identified in live births. Diagnosis of a coinherited neuromuscular genetic disorder in these individuals is often challenging based on the severity and variability of the phenotype resulting from the genomic imbalance. Herein, we report on a 4-month-old male with multiple congenital anomalies, craniosynostosis, dysmorphic features, and hypotonia. Karyotype analysis revealed an abnormal male karyotype: 46,XY,der(3)(3;7)(p25;q36), with partial monosomy of 3pter and partial trisomy of 7qter. The targeted array-based comparative genomic hybridization (array-CGH) validated the cytogenetic abnormality, with further elucidation of trisomy of the Sonic Hedgehog (SHH) locus on chromosome 7. Based on the severity of hypotonia in this infant, molecular analysis for spinal muscular atrophy (SMA) was performed and the common homozygous deletion of exon 7 in the survival of motor neuron 1 gene (SMN1) was identified. This case demonstrates the challenges in diagnoses of coexisting genetic disorders in infants with neuromuscular disease. A high index of suspicion in such cases is essential for appropriate case management and family risk assessment.
AB - Unbalanced chromosomal abnormalities are frequent and account for about 10% of all chromosomal abnormalities identified in live births. Diagnosis of a coinherited neuromuscular genetic disorder in these individuals is often challenging based on the severity and variability of the phenotype resulting from the genomic imbalance. Herein, we report on a 4-month-old male with multiple congenital anomalies, craniosynostosis, dysmorphic features, and hypotonia. Karyotype analysis revealed an abnormal male karyotype: 46,XY,der(3)(3;7)(p25;q36), with partial monosomy of 3pter and partial trisomy of 7qter. The targeted array-based comparative genomic hybridization (array-CGH) validated the cytogenetic abnormality, with further elucidation of trisomy of the Sonic Hedgehog (SHH) locus on chromosome 7. Based on the severity of hypotonia in this infant, molecular analysis for spinal muscular atrophy (SMA) was performed and the common homozygous deletion of exon 7 in the survival of motor neuron 1 gene (SMN1) was identified. This case demonstrates the challenges in diagnoses of coexisting genetic disorders in infants with neuromuscular disease. A high index of suspicion in such cases is essential for appropriate case management and family risk assessment.
KW - Chromosomal aberrations
KW - Concurrent occurrence
KW - SMA
UR - http://www.scopus.com/inward/record.url?scp=61749101774&partnerID=8YFLogxK
U2 - 10.1002/ajmg.a.32667
DO - 10.1002/ajmg.a.32667
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C2 - 19215052
AN - SCOPUS:61749101774
VL - 149
SP - 515
EP - 518
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 1552-4825
IS - 3
ER -