DEBORA ROMEO BERTOLA
Projetos de Pesquisa
Unidades Organizacionais
Instituto da Criança, Hospital das Clínicas, Faculdade de Medicina - Médico
BIO, IB
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
BIO, IB
LIM/36 - Laboratório de Pediatria Clínica, Hospital das Clínicas, Faculdade de Medicina
96 resultados
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- Mucopolysaccharidosis Type IVA: Evidence of Primary and Secondary Central Nervous System Involvement(2014) BORLOT, Felippe; ARANTES, Paula Ricci; QUAIO, Caio Robledo; FRANCO, Jose Francisco da Silva; LOURENCO, Charles Marques; GOMY, Israel; BERTOLA, Debora Romeo; KIM, Chong AeMucopolysaccharidosis type IVA is a rare lysosomal storage disease caused by a deficiency of N-acetylgalactosamine 6-sulfatase. Studies usually focus on skeletal abnormalities and their consequences. This study explores the neurological manifestations in a cohort of mucopolysaccharidosis type IVA patients, with a detailed focus on brain and spinal magnetic resonance imaging (MRI) findings. We performed a cross-sectional study involving nine patients with a biochemical confirmation of mucopolysaccharidosis type IVA. The protocol consists of a comprehensive clinical examination and brain and spinal cord MRI analysis for all subjects. The mean age was 16.4 years (+/- 5.7) and the mean onset of symptoms was 11.5 months (+/- 6.3). Overall, cognition was spared in all but one patient and motor weakness was a constant finding in all patients. Deep sensation impairment was found in six patients. The brain MRIs showed non-specific white matter changes in two patients. Other abnormalities such as clival hypoplasia, basilar invagination, and arachnoid cists appeared in seven of the nine patients. Eight patients presented spinal cord compression, and in three of them, two spinal levels were compromised. Odontoid hypoplasia and degenerative features in the neuroaxis were present in all patients. Our experience with mucopolysaccharidosis type IVA patients supports the evidence of central nervous system involvement. We emphasize the importance of regular clinical assessments with complete MRI studies, as an attempt to detect the early signs of spinal cord compression. This evaluation may be especially important before surgical interventions, as occult lesions may become symptomatic and promote postoperative unfavorable outcomes. (c) 2014 Wiley Periodicals, Inc.
- Nationwide questionnaire data of 229 Williams-Beuren syndrome patients using WhatsApp tool(2021) PIRES, Lucas Vieira Lacerda; RIBEIRO, Rogerio Lemos; SOUSA, Adriana Modesto de; LINNENKAMP, Bianca Domit Werner; PONTES, Sue Ellen; TEIXEIRA, Maria Cristina Triguero Veloz; BEFI-LOPES, Debora Maria; HONJO, Rachel Sayuri; BERTOLA, Debora Romeo; KIM, Chong AeBackground: Williams-Beuren syndrome is a multisystemic disorder caused by a microdeletion of the 7q 11.23 region. Although familial cases with autosomal dominant inheritance have been reported, the vast majority are sporadic. Objective: To investigate the main complaints and clinical findings of patients with Williams-Beuren syndrome. Methods: A total of 757 parents of patients registered in the Brazilian Association of Williams-Beuren Syndrome (ABSW) received a questionnaire via WhatsApp from March to July 2017. Results: In total, 229 parents answered the survey. Age of diagnosis ranged from 2 days to 34 years (median: 3 years). The main clinical findings reported by the parents were abdominal colic (83.3%), failu re to thrive (71.5%), feeding difficulty in the first year (68.9%), otitis (56.6%), urinary tract infections (31.9%), precocious puberty (27.1%) and scoliosis (15.9%). Cardiac defects were present in 66% of patients, and the most frequent defect was supravalvular aortic stenosis (36%). Arterial hypertension was reported in 23%. Hypercalcemia was reported in 10.5% of patients, mainly during the first year of life. Hyperacusis and hypersociability were common complaints (both present in 89%). Other behavioral and neuropsychiatric symptoms reported by the parents included attention deficit (89%), anger crises (83%), excessive fear (66%), depression (64%), anxiety (67%) and hypersexuality(33%).The most common complaints were hypersensitivity to sounds, talkative personality, emotional dependence and learning difficulties. In 98.3%, the parents denied family history. Conclusions: Williams-Beuren syndrome requires close follow-up with different medical specialties due to their variable clinical comorbidities, including language and school learning difficulties, behavioral and psychiatric problems.
- Achondroplasia in Latin America: practical recommendations for the multidisciplinary care of pediatric patients(2022) LLERENA JR., Juan; KIM, Chong Ae; FANO, Virginia; ROSSELLI, Pablo; COLLETT-SOLBERG, Paulo Ferrez; MEDEIROS, Paula Frassinetti Vasconcelos de; PINO, Mariana del; BERTOLA, Debora; LOURENCO, Charles Marques; CAVALCANTI, Denise Pontes; FELIX, Temis Maria; ROSA-BELLAS, Antonio; ROSSI, Norma Teresa; CORTES, Fanny; ABREU, Flavia; CAVALCANTI, Nicolette; RUZ, Maria Cecilia Hervias; BARATELA, WagnerBackground Achondroplasia is the most common bone dysplasia associated with disproportionate short stature, and other comorbidities, such as foramen magnum stenosis, thoracolumbar kyphosis, lumbar hyperlordosis, genu varum and spinal compression. Additionally, patients affected with this condition have higher frequency of sleep disorders, ear infections, hearing loss and slowed development milestones. Considering these clinical features, we aimed to summarize the regional experts' recommendations for the multidisciplinary management of patients with achondroplasia in Latin America, a vast geographic territory with multicultural characteristics and with socio-economical differences of developing countries. Methods Latin American experts (from Argentina, Brazil, Chile and Colombia) particiated of an Advisory Board meeting (October 2019), and had a structured discussion how patients with achondroplasia are followed in their healthcare centers and punctuated gaps and opportunities for regional improvement in the management of achondroplasia. Results Practical recommendations have been established for genetic counselling, prenatal diagnosis and planning of delivery in patients with achondroplasia. An outline of strategies was added as follow-up guidelines to specialists according to patient developmental phases, amongst them neurologic, orthopedic, otorhinolaryngologic, nutritional and anthropometric aspects, and related to development milestones. Additionally, the role of physical therapy, physical activity, phonoaudiology and other care related to the quality of life of patients and their families were discussed. Preoperative recommendations to patients with achondroplasia were also included. Conclusions This study summarized the main expert recommendations for the health care professionals management of achondroplasia in Latin America, reinforcing that achondroplasia-associated comorbidities are not limited to orthopedic concerns.
- Multiple, diffuse schwannomas in a RASopathy phenotype patient with germline KRAS mutation: a causal relationship?(2012) BERTOLA, D. R.; PEREIRA, A. C.; BRASIL, A. S.; SUZUKI, L.; LEITE, C.; FALZONI, R.; TANNURI, U.; POPLAWSKI, A. B.; JANOWSKI, K. M.; KIM, C. A.; MESSIAEN, L. M.
- Genetic Disorders in Prenatal Onset Syndromic Short Stature Identified by Exome Sequencing(2019) HOMMA, Thais Kataoka; FREIRE, Bruna Lucheze; KAWAHIRA, Rachel Sayuri Honjo; DAUBER, Andrew; FUNARI, Mariana Ferreira de Assis; LERARIO, Antonio Marcondes; NISHI, Mirian Yumie; ALBUQUERQUE, Edoarda Vasco de; VASQUES, Gabriela de Andrade; COLLETT-SOLBERG, Paulo Ferrez; SUGAYAMA, Sofia Mizuho Miura; BERTOLA, Debora Romeo; KIM, Chong Ae; ARNHOLD, Ivo Jorge Prado; MALAQUIAS, Alexsandra Christianne; JORGE, Alexander Augusto de LimaObjective To perform a prospective genetic investigation using whole exome sequencing of a group of patients with syndromic short stature born small for gestational age of unknown cause. Study design For whole exome sequencing analysis, we selected 44 children born small for gestational age with persistent short stature, and additional features, such as dysmorphic face, major malformation, developmental delay, and/or intellectual disability. Seven patients had negative candidate gene testing based on clinical suspicion and 37 patients had syndromic conditions of unknown etiology. Results Of the 44 patients, 15 (34%) had pathogenic/likely pathogenic variants in genes already associated with growth disturbance: COL2A1 (n = 2), SRCAP (n = 2), AFF4, ACTG1, ANKRD11, BCL11B, BRCA1, CDKN1C, GINS1, INPP5K, KIF11, KMT2A, and POC1A (n = 1 each). Most of the genes found to be deleterious participate in fundamental cellular processes, such as cell replication and DNA repair. Conclusions The rarity and heterogeneity of syndromic short stature make the clinical diagnosis difficult. Whole exome sequencing allows the diagnosis of previously undiagnosed patients with syndromic short stature.
bookPart Displasias esqueléticas(2017) KIM, Chong Ae; BERTOLA, Débora Romeo; ALBANO, Lilian Maria José- Impact of ERT and follow-up of 17 patients from the same family with a mild form of MPS II(2022) STEPHAN, Bruno de Oliveira; QUAIO, Caio Robledo; SPOLADOR, Gustavo Marquezani; PAULA, Ana Carolina de; CURIATI, Marco Antonio; MARTINS, Ana Maria; LEAL, Gabriela Nunes; TENORIO, Artur; FINZI, Simone; CHIMELO, Flavia Teixeira; MATAS, Carla Gentile; HONJO, Rachel Sayuri; BERTOLA, Debora Romeo; KIM, Chong AeBackground: Mucopolysaccharidosis type II, also known as Hunter syndrome, is a rare X-linked recessive disorder caused by deficiency of the lysosomal enzyme Iduronate-2-Sulfatase (IDS), leading to progressive accumulation of Glycosaminoglycans (GAGs) in several organs. Over the years, Enzyme Replacement Therapy (ERT) has provided significant benefits for patients, retarding the natural progression of the disease. Results: The authors evaluated 17 patients from the same family with a mild form of MPS type II; the proband had developed acute decompensated heart failure refractory to clinical measurements at 23 years and needed a rather urgent heart transplant; however, he died from surgical complications shortly after the procedure. Nevertheless, subsequent to his tragic death, 16 affected male relatives were detected after biochemical tests identifying the low or absent activity of the IDS enzyme and confirmed by molecular analysis of the IDS gene. Following diagnosis, different options of treatment were chosen: 6 patients started ERT with Elaprase (R) (Idursulfase) soon after, while the other 10 remained without ERT. Eventually, 4 patients in the latter group began ERT with Hunterase (R) (Idursulfase Beta). None presented adverse effects to either form of the enzyme. Among the 6 individuals without any ERT, two died of natural causes, after reaching 70 years. Despite the variable phenotype within the same family (mainly heart dysfunctions and carpal tunnel syndrome), all 14 remaining patients were alive with an independent lifestyle. Conclusion: Here, the authors report the variable progress of the disease with and without ERT in a large Brazilian family with a slowly progressive form of MPS II, harboring the same missense variant in the IDS gene.
- Rare variants in SOS2 and LZTR1 are associated with Noonan syndrome(2015) YAMAMOTO, Guilherme Lopes; AGUENA, Meire; GOS, Monika; HUNG, Christina; PILCH, Jacek; FAHIMINIYA, Somayyeh; ABRAMOWICZ, Anna; CRISTIAN, Ingrid; BUSCARILLI, Michelle; NASLAVSKY, Michel Satya; MALAQUIAS, Alexsandra C.; ZATZ, Mayana; BODAMER, Olaf; MAJEWSKI, Jacek; JORGE, Alexander A. L.; PEREIRA, Alexandre C.; KIM, Chong Ae; PASSOS-BUENO, Maria Rita; BERTOLA, Debora RomeoBackground Noonan syndrome is an autosomal dominant, multisystemic disorder caused by dysregulation of the RAS/mitogen activated protein kinase (MAPK) pathway. Heterozygous, pathogenic variants in 11 known genes account for approximately 80% of cases. The identification of novel genes associated with Noonan syndrome has become increasingly challenging, since they might be responsible for very small fractions of the cases. Methods A cohort of 50 Brazilian probands negative for pathogenic variants in the known genes associated with Noonan syndrome was tested through whole-exome sequencing along with the relatives in the familial cases. Families from the USA and Poland with mutations in the newly identified genes were included subsequently. Results We identified rare, segregating or de novo missense variants in SOS2 and LZTR1 in 4% and 8%, respectively, of the 50 Brazilian probands. SOS2 and LZTR1 variants were also found to segregate in one American and one Polish family. Notably, SOS2 variants were identified in patients with marked ectodermal involvement, similar to patients with SOS1 mutations. Conclusions We identified two novel genes, SOS2 and LZTR1, associated with Noonan syndrome, thereby expanding the molecular spectrum of RASopathies. Mutations in these genes are responsible for approximately 3% of all patients with Noonan syndrome. While SOS2 is a natural candidate, because of its homology with SOS1, the functional role of LZTR1 in the RAS/MAPK pathway is not known, and it could not have been identified without the large pedigrees. Additional functional studies are needed to elucidate the role of LZTR1 in RAS/MAPK signalling and in the pathogenesis of Noonan syndrome.
- New insights in mucopolysaccharidosis type VI: Neurological perspective(2014) BORLOT, Felippe; ARANTES, Paula Ricci; QUAIO, Caio Robledo; FRANCO, Jose Francisco da Silva; LOURENCO, Charles Marques; BERTOLA, Debora Romeo; KIM, Chong AeObjective: Mucopolysaccharidosis type VI is a rare autosomal recessive storage disorder, caused by deficiency of arylsulfatase B. Data on neurological involvement in mucopolysaccharidosis type VI patients under enzyme-replacement therapy are limited. This study explores the neurological and magnetic resonance imaging findings in a sample of mucopolysaccharidosis type VI patients receiving enzyme-replacement therapy. Methods: We performed a cross-sectional study including six patients with biochemical confirmation of mucopolysaccharidosis type VI and at least 105 consecutive weeks (two years) receiving intravenous enzyme-replacement therapy. The protocol included a comprehensive clinical examination, brain and spinal cord magnetic resonance imaging for all subjects. Results: Overall, cognition was spared, while we found presence of hearing impairment, increasing in deep tendon reflexes and deep sensation reduction in three patients. In addition to the classical abnormalities related to other types of mucopolysaccharidosis, imaging studies demonstrated morphological changes in anatomy of middle cranial fossa and sella shape. Even in asymptomatic or mild compromised patients, spinal cord compression was found. In four patients we noticed atlantoaxial joint subluxation and three had cervical spinal stenosis. Degenerative processes involving vertebral column, including discal protrusion and axis abnormalities, were present in all patients. Conclusions: Neuroaxis involvement was a universal finding and neurological examination might not predict the severity of the disease in course. Image studies should not be performed according exclusively clinical parameters for these patients, once we have demonstrated that neurological involvement may be silent in these patients.
conferenceObject Novel mutations in fibronectin associated with metaphyseal fractures - Expanding the phenotype of patients with a subtype of spondylomethaphyseal dysplasia with ""corner fractures""(2018) ALM, Jessica J.; COSTANTINI, Alice; VALTA, Helena; BARATANG, Nissan Vida; YAP, Patrick; BERTOLA, Debora; YAMAMOTO, Guilherme; KIM, Chong A.; CHEN, Jiani; WIERENGA, Klaas J.; FANNING, Elizabeth A.; ESCOBAR, Luis; MCWALTER, Kirsty; MCLAUGHLIN, Heather; WILLAERT, Rebecca; BEGTRUP, Amber; REINHARDT, Dieter P.; MAKITIE, Outi; CAMPEAU, Philippe M.