RESUMO
Variants in EFEMP1, encoding Fibulin-3, were previously reported as a rare cause of heritable connective tissue disorder (HCTD) with recurrent hernias and joint hypermobility. We report three new cases with biallelic or monoallelic EFEMP1 variants and severe hernia phenotypes. Two male siblings of 10 and 13 years old presented with marfanoid habitus, recurrent inguinal and umbilical hernias, generalized joint hypermobility, and scoliosis. Parents and halfsiblings reported joint hypermobility and umbilical hernias. The eldest boy died at age 16 from incarcerated gastrointestinal herniation complicated by gastric and bowel necrosis with perforation. Autopsy revealed widespread intestinal diverticula. Immunohistochemistry of skin and fascia tissue did not reveal any abnormalities, including normal staining of elastic fibers. Both siblings harbored compound heterozygous likely pathogenic EFEMP1 variants (c.1320 + 2T > A, p.? and c.698G > A, p.Gly233Asp). An unrelated 58-year-old male had marfanoid features, high myopia, recurrent diaphragmatic and inguinal hernias, and chronic gastrointestinal dilatation with severe malabsorption. Both his dizygotic twin-brother and mother had recurrent hernias and high myopia. This man died at 59 years of age, and autopsy showed extensive diaphragmatic herniation, bowel diverticula, and pulmonary emphysema. A heterozygous EFEMP1 splice-variant (c.81 + 1G > A, p.?) was identified, causing exon skipping leading to a start-loss. Targeted genome reanalysis nor RNA-sequencing revealed a second variant at the other allele. The reported individuals expand the clinical and pathological phenotypes of EFEMP1-related disease, a distinct entity within the spectrum of HCTD. The severe and recurrent hernias, gastrointestinal dilatation, and diverticulosis result in an increased risk for life-threatening complications, demanding early recognition and close monitoring.
RESUMO
Delayed spinal cord injury (SCI) hours or days after surgery, with uneventful monitoring and initial normal postoperative neurological examination, is a rare complication. Based on anecdotal evidence, the risk of delayed spinal cord injury might be higher than previously assumed. Therefore the aim of this study was to determine the risk of delayed SCI after pediatric spinal deformity surgery between 2013-2019 in the Netherlands. The total number of pediatric spinal deformity surgeries performed for scoliosis or kyphosis between 2013-2019 was obtained from the Dutch National Registration of Hospital Care. All eleven Dutch hospitals that perform pediatric spinal deformity surgery were contacted for occurrence of delayed SCI. From the identified patients with delayed SCI, the following data were collected: patient characteristics, details about the SCI, the surgical procedure, management and degree of improvement.2884 pediatric deformity surgeries were identified between 2013-2019. Seven patients (0.24%) with delayed SCI were reported: 3 idiopathic, 2 neuromuscular (including 1 kypho-scoliosis) and 2 syndromic scoliosis. The risk of delayed SCI after pediatric deformity surgery was 1:595 in idiopathic scoliosis, 1:214 in syndromic scoliosis, 1:201 in neuromuscular scoliosis. All seven patients had a documented normal neurological examination in the first postoperative period; neurological deficits were first diagnosed at a median 16h (range 2.5-40) after surgery. The risk of delayed SCI after pediatric deformity surgery is higher than previously reported, especially in patients with non-idiopathic scoliosis. Regular postoperative testing for late neurologic deficit should be performed for timely diagnosis and management of this devastating complication.