ABSTRACT
Abstract Introduction Mucopolysaccharidoses (MPS) can lead to cervical spinal cord compression (SCC). Diagnostic scores for SCC in MPS use the obliteration of the passage of cerebrospinal fluid in the anterior and posterior spinal cord in the sagittal section of magnetic resonance imaging (MRI). The spinal cord occupation ratio (SCOR) published, by Nouri et al (2018), establishes the spinal cord filling index for the spinal cord, identifying disproportionate spinal cord occupation in the canal. When evaluating congenital canal stenosis, the risk of spinal cord injury has been considered increased when the SCOR is ≥70% in the median sagittal plane or ≥ 80% in the axial plane. Although these values have not been validated for MPS populations, they could be useful. Objective To verify the SCOR in MPS patients with diagnosis of cervical SCC comparing the SCOR with other markers proposed in the existing MPS SCC scores, such as the extent of gliosis, clinical impact and the SCC assessment as represented by the obliteration of CSF flow. Methods We reviewed imaging tests of the cervical spine from MPS patients with previously confirmed SCC, using the SCOR measure in the median sagittal plane, evaluation of the presence and extent of spinal gliosis on MRI, evaluation of the clinical impact using a clinical score and evaluation of the images for the obliteration of cerebral spinal fluid (CSF) flow. Results Thirty-one MRI of 24 different patients were included. The average SCOR was 87.1%. This was lower (81.6%) in patients without gliosis, when compared to those with focal (90.5%) and extensive (97%) gliosis. The only patient with gliosis associated with a lacunar lesion, resulting from an acute compressive injury, had a 68% SCOR, due to the atrophic spinal cord injury. As expected, SCOR was higher in patients with total or partial CSF obliteration, but one among the 3 patients without CSF flow obliteration, with a 76% SCOR, had already developed focal gliosis and mild clinical abnormalities. Patients with more extensive gliosis had higher clinical scores. Four patients had more than one imaging scan evaluated. SCOR upward trend showed an annual average increase of 3.8%. Discussion & Conclusions The use of SCOR allows the diagnosis of cervical spinal canal stenosis in an objective way. It is possible that the cut-off values used by Nouri et al in patients with congenital stenosis could be useful to diagnose cervical stenosis in MPS patients, preceding the finding of CSF flow obstruction, presence of gliosis or clinical abnormalities. Furthermore, the use of SCOR may assist in the longitudinal evaluation of disease progression. Better follow-up and timely diagnosis allows for scheduling of surgery at the best clinical moment, minimizing complications.
ABSTRACT
Introdução: A Síndrome de Cornelia de Lange (CdLS) (OMIM: 122470) é uma doença genética rara com quadro clínico e fenótipo variáveis, compreendendo um grupo de doenças denominado coesinopatias. Entre suas principais características: deficiência intelectual (DI), baixa estatura, doença do refluxo gastroesofágico (DRGE), hipertricose, dismorfismos faciais e anomalias em membros superiores. O diagnóstico pode ser dificultado nos quadros atenuados. O objetivo do estudo foi determinar os principais achados clínicos e moleculares em uma série de pacientes com o diagnóstico clínico de CdLS.Métodos: Foram avaliados 33 pacientes com diagnóstico clínico e/ou molecular de CdLS (18 sexo feminino e 15 masculino) com idades entre 1 mês e 43 anos. Aplicou-se um escore clínico visando a categorização dos pacientes baseado em Kline et al. (2018). Esta ferramenta utiliza sinais clínicos para determinar as formas clássicas (n: 23), não clássicas (n: 6) e os casos que, apesar de não se enquadrarem nestas categoriais, também deveriam ser testados molecularmente para a síndrome (n: 4).Resultados: Atraso do desenvolvimento/DI, distúrbios de comportamento, déficit de crescimento e DRGE foram as comorbidades mais prevalentes. Entre as dismorfias: sinofris, micrognatia, narinas antevertidas e comissura labial desviada para baixo. Os achados moleculares nos pacientes submetidos ao sequenciamento completo do exoma revelaram 6 variantes em NIPBL (46%), 2 variantes em SMC1A (15%), 1 variante em SMC3, 1 variante em HDAC8, 1 variante em AHDC1 e 2 resultados negativos.Conclusões: Os dados obtidos revelaram uma grande heterogeneidade de apresentação da síndrome. A utilização de escores clínicos podem auxiliar no diagnóstico de CdLS.
Introduction: Cornelia de Lange syndrome (CdLS) (OMIM: 122470) is a rare genetic disease with variable clinical presentation and phenotype, part of a group of disorders termed cohesinopathies. Intellectual disability, growth retardation, gastroesophageal reflux disease, hypertrichosis, facial dysmorphisms, and anomalies of the upper limbs are the most common clinical characteristics. Diagnosis may be difficult, especially in attenuated presentations. The aim of this study was to determine the main clinical and molecular findings in a series of patients with clinical diagnosis of CdLS.Methods: Thirty-three patients with typical clinical and/or molecular diagnosis of CdLS (18 female and 15 male) aged between 1 month and 43 years were evaluated. A clinical score was applied to categorize patients. This tool uses clinical signs to determine the classic (n: 23) and nonclassic (n: 6) forms, in addition to a category to suggest which cases should be molecularly tested for the syndrome (n: 4).Results: Developmental delay/intellectual disability, behavioral disorders, growth retardation, and gastroesophageal reflux disease were the most prevalent comorbidities. Dysmorphic features included synophrys micrognathia, anteverted nostrils, and labial commissure turning downwards. Molecular findings in those who underwent whole exome sequencing revealed 6 variants in NIPBL (46%), 2 variants in SMC1A (15%), 1 variant in SMC3, 1 variant in HDAC8, 1 variant in AHDC1, and 2 negative results.Conclusions: The data revealed a great heterogeneity in the presentation of the syndrome. The use of clinical scores can help in the diagnosis of CdLS.