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Coexistence of an unbalanced chromosomal rearrangement and spinal muscular atrophy in an infant with multiple congenital anomalies
Author(s) -
BenShachar Shay,
Bidwa Bhattacharjee M.,
Potocki Lorraine,
Lalani Seema R.
Publication year - 2009
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.32667
Subject(s) - spinal muscular atrophy , hypotonia , comparative genomic hybridization , biology , karyotype , monosomy , craniosynostosis , genetics , pathology , medicine , chromosome , gene
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. © 2009 Wiley‐Liss, Inc.