A 37-year-old woman with schwannomatosis, who has undergone 10 neurosurgical procedures: the first case in Poland with the SMARC1B gene mutation

Mutations of the SMARC1B gene (also known as INI1, hSNF5, and BA547) are most often associated with the diagnosis of schwannomatosis. Most cases occur sporadically and only 15%–25% are inherited. SMARCB1 germline mutations have been found in 45% of familial probands and 9% of sporadic patients.¹ Schwannomatosis is a disease with multiple schwannomas (less commonly meningiomas) that are clinically distinct from those in neurofibromatosis type I (NF1) and neurofibromatosis type II (NF2). The most common location of the tumors are the peripheral and spinal nerves. Meningiomas occur in about 5% of the patients and have only been reported in individuals with SMARCB1-related schwannomatosis.² The clinical manifestation of schwannomatosis is often pain caused by tumor compression of the peripheral nerves. Surgical resection of the tumor is the only treatment option.³

In this study, we present a case of a 37-year-old woman diagnosed with schwannomatosis. The genetic tests indicated a c.233-1G>Ap. heterozygous mutation in the intron 2/8 of the SMARCB1 gene (MANE Select NM_003073.5). The study was carried out using a next generation sequencing gene panel including all exons of NF1, NF2, KIT, SMARC1B, and SPRED1 on the NextSeq500 sequencer (Illumina, San Diego, California, United States). The average depth of the sequence coverage was 53.7, with a quality threshold of 95%.

The observed mutation was neither previously described in the literature nor recorded in popular genome databases (gnomAD, 1000 Genomes, and other). The variant is classified as likely pathogenic according to the American College of Medical Genetics rules, due to its extremely low frequency and highly likely disruptive effect on splicing in bioinformatics analyses, which leads to the absence of a functional protein.

The patient has been treated for many years due to multiple schwannomas within the nervous system, including 8 neurosurgical operations. Physical examination showed clear consciousness, normal vision, no headache or dizziness, no skin lesions in the armpits and groin, and no café-au-lait spots. Limb strength and mobility were normal but we noted weakened superficial sensation in the lateral surface of the right thigh and right tibia, as well as positive Laseque sign on the left limb at 50 degrees. The patient also reported severe pain in the thoracolumbar junction radiating to the left thigh. Magnetic resonance imaging (MRI) of the thoracic (Th) and lumbosacral spine revealed 5 extramedullary tumors ranging in diameter from 2 mm to 14 mm (Figure 1A–1D). The largest one, at the level of Th11–Th12 on the left side, was compressing the terminal cone of the spinal cord. The patient was qualified for surgery and the largest schwannoma was removed. Histopathologic examination revealed cellular schwannoma of grade 1 according to the World Health Organization classification of central nervous system tumors. The neoplasm was composed exclusively of cellular Antoni A areas with closely packed spindle cells with mild atypia and focal mitotic activity. Only few poorly formed Verocay bodies were found, and there was no necrosis. The tumor cells showed S100 positivity and Ki-67 index up to 15% (Figure 1E and 1F). After the surgery, the patient was conscious, extubated, and presented complete sensorimotor paralysis from the L1 level (grade A on the American Spinal Injury Association scale). Steroid therapy was implemented and slow improvement in the mobility of the lower limbs was observed. The patient presented paresis of the lower limbs of grade 2 to 3 on the Lovett scale. Postoperative MRI confirmed that the largest schwannoma at the Th11–Th12 level was completely resected (Figure 1G).

After 2 weeks, due to increasing paresthesia and paresis of the upper limbs, MRI of the cervical (C) spine was performed, showing an extramedullary tumor measuring 35 mm × 14 mm × 22 mm in the posterior part of the spinal canal, at the C3–C4 level, with a significant stenosis of the spinal canal (Figure 1H–1K). There was also a tumor in the right parapharyngeal space visible on MRI (Figure 1I). The patient was operated on again. C3–C4 laminectomy was performed, and the schwannoma was removed. After the procedure, slow improvement in the neurological condition was observed, with paresis of the lower limbs of grade 2 to 3 on the Lovett scale, more severe in the right lower limb. The 1-year follow-up showed slight improvement in movement of the lower limbs (up to grade 3 to 4 on the Lovett scale). The most problematic issue turned out to be effective analgesic treatment, which is a very important component of postoperative care in this type of patients. The patient’s written consent was obtained for the publication of this case report.

Neurosurgeons are familiar with NF1 and NF2 phacomatoses⁴ but should be aware that NF2 and schwannomatosis are genetically distinct syndromes with overlapping phenotypes.⁵ We described the first case of a patient with schwannomatosis in Poland. Expanding knowledge in this field will certainly improve patient care.