G.P.233: Neuroblastoma in a patient with spinal muscular atrophy (SMA) Type I: Is it just a coincidence?

Abstract

SMA is an autosomal recessive disorder characterized by progressive degeneration of anterior horn cells of the spinal cord resulting in hypotonia, skeletal muscle atrophy, and weakness. Neuroblastoma is the most common cancer, and extracranial solid cancer in childhood, arising from any neural crest element of the sympathetic nervous system. A 4-month-old male infant presented with abdominal mass, and hypotonia. Phenotype was consistent with SMA type I, and diagnosis was further confirmed with SMN1 gene deletion. A tru-cut biopsy from the mass was compatible with the diagnosis of neuroblastoma histologically. The tumor had no amplification of N-myc, but had loss of chromosome 1p36, and gain of chromosome 17q25. There are only a few case reports of SMA type II and/or III with alveolar rhabdomyosarcoma. Studies with neuroblastoma × spinal cord hybrid cell lines which are used as a model for developing motor neuron revealed that, SMN1 gene is the key regulator of nuclear architecture in differentiating neuroblastoma cells. Cells unable to sufficiently increase their SMN levels may differentiate less efficiently, and be susceptible to damage or death. One speculation can be, SMN1 deletion in SMA may lead to incomplete differentiation of neurons, and decreased viability of cells and immature forms may escape apoptosis, which can develop malign transformation. Nevertheless, regarding the lack of evidence, the coexistence of these two pathologies may still be a coincidence. The follow-up of this patient is challenging in terms of the natural history of SMA type I, and decisions for chemotherapy protocols.