Clinical characteristics and gene analysis of SMC1A gene related disorders / 中华神经科杂志

Objective:To analyze the clinical characteristics and genetic features of SMC1A gene related disorders. Methods:The data of 5 children with SMC1A gene variants were collected from Children′s Hospital of Fudan University from February 2018 to January 2022. The clinical features, electroencephalogram (EEG), brain imaging and gene testing results were summarized. Results:Among the 5 patients, 4 are females and 1 is male. Two female cases are siblings. One boy had dysmorphic features, consisting of bilateral ptosis, synophrys, a short nose and upturned nasal tip. He also had patent foramen ovale plus atrial septal defect, unilateral cryptorchidism and microcephaly. Three cases had microcephaly. Two girls had patent foramen ovale, and 2 girls had microcephaly. Four cases had epilepsy, and age at seizure onset ranged from 2 to 52 months. Multiple seizure types were observed, including bilateral tonic clonic seizures in 2 patients, and focal seizures in 3 patients. The seizures in 3 cases were in cluster. All patients had developmental delay, including 1 patient with mild and 4 patients with moderate to severe developmental delay. Three patients had slow background activity in EEG. Interictal EEG showed abnormal discharges in 4 patients, including focal discharges in 3 cases and generalized discharges in 1 case. Brain magnetic resonance imaging was normal in 3 patients and showed mild cortical thickening in 1 case. All cases harbored 4 SMC1A gene variants, including 2 missense variants and 2 frameshift variants (c.580_587del, c.2699delG, c.3362G>A, c.1486C>T). Three cases harbored heterozygous SMC1A variants and 2 cases carried somatic mosaic SMC1A variants with 17.5% and 88.1% mosaicism in peripheral blood. The follow-up lasted for 3 months to 4 years. The epilepsy was refractory in 2 cases. During the follow-up, all cases had very slow developmental progress or developmental retardation. All cases had different levels of growth retardation. The scores of Cornelia de Lange syndrome (CdLS) phenotypes in 5 cases were 2-6. One case had the combined phenotypes of atypical CdLS and developmental epileptic encephalopathy (DEE). The phenotype was atypical CdLS in 1 case and DEE in 1 case. The phenotypes of 2 cases with SMC1A missense variants were mild, manifesting as non-refractory epilepsy and moderate to severe developmental delay. Conclusions:All of cases with SMC1A gene variants have developmental delay. Most of the patients have clusters of seizures and some dysmorphisms. The phenotypes of SMC1A gene related disorders are diverse. Except CdLS and DEE, there are some patients with mild phenotype due to missense variants of SMC1A gene.

Síndrome de Cornelia de Lange: análise de uma série de 33 pacientes em um centro de referência / Cornelia de Lange syndrome: analysis of a series of 33 patients in an excellence center

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.

Audiological profile of individuals with Cornelia de Lange syndrome: an integrative review / Perfil audiológico de indivíduos com síndrome de Cornelia de Lange: revisão integrativa da literatura

ABSTRACT Purpose: to describe the audiological profile of patients with Cornelia de Lange syndrome (CdLS) in an integrative review of the literature. Methods: after developing the research question, articles were searched in six databases (EMBASE, ISI of Knowledge, LILACS, MEDLINE/PubMed, SciELO, and Scopus) and in sources of information (Google Scholar, OpenGrey, and ProQuest), with the following descriptors: audiology, hearing loss, deafness, hearing disorders, and Cornelia de Lange syndrome. This review was registered in Prospero under number CRD42020191481. National and international studies were considered for analysis, using the PECO acronym. The risk of bias in the studies was analyzed with Joanna Briggs Institute protocols. Then, the studies were described and analyzed. Results: of the 1,080 articles found, 12 met the inclusion criteria. Audiological results showed that individuals with CdLS can have hearing loss - conductive hearing losses were the most frequent impairments, corresponding to 49.20% of individuals with CdLS assessed, followed by sensorineural hearing losses (13.49%). The degrees of hearing loss ranged from mild to profound. Conclusion: individuals presented with CdLS often have hearing loss, mainly due to middle ear changes, with degrees ranging from mild to profound.

RESUMO Objetivo: descrever o perfil audiológico de pacientes com Síndrome de Cornelia de Lange (SCdL), por meio de uma revisão integrativa da literatura. Métodos: após formulação da pergunta, realizou-se uma busca em seis bases de dados (Embase, ISI of Knowledge, Lilacs, Medline/PubMed, Scielo e Scopus), e fontes de informação (Google Acadêmico, OpenGrey e Proquest), com os descritores: audiologia, perda auditiva, surdez, transtornos da audição e Síndrome de Cornelia de Lange. Esta revisão foi cadastrada no Próspero, sob número CRD42020191481. Foram considerados para análise, estudos nacionais e internacionais, utilizando o direcionamento do acrônimo PECO. Para análise do risco de viés dos estudos, utilizou-se os protocolos do Instituto Joanna Briggs. Após isso, os estudos foram descritos e analisados. Resultados: dos 1.080 artigos encontrados, 12 atenderam aos critérios de inclusão. Nos resultados audiológicos, constatou-se que indivíduos com SCdL podem apresentar perda auditiva, sendo que o comprometimento pela perda auditiva condutiva foi o mais frequente, correspondendo a 49,20% dos indivíduos com SCdL avaliados, seguido pela perda auditiva neurossensorial (13,49%). O grau de perda auditiva variou de leve à profundo. Conclusão: indivíduos com SCdL frequentemente apresentam perda auditiva, decorrente principalmente de alterações de orelha média, com graus variando de leve a profundo.

Cornelia de Lange syndrome with recurrent seizures and SMC1A gene c. 2923C > T mutation: a case report and literature review / 中华实用儿科临床杂志

Objective:To explore the characteristics, clinical manifestations and gene mutation types of Cornelia de Lange syndrome (CdLs), and to improve the understanding of the disease.Methods:Clinical data and gene test results of a pediatric case of CdLs diagnosed in the First Affiliated Hospital of Xinxiang Medical University in August 2019 were analyzed retrospectively.Results:A female patient with 2 years and 8 months old presented a special appearance with a low and flat nose, a wide eye distance, audition ears, a downward inclination of the mouth corner, a high arch of the jaw and a small jaw deformity, who had recurrent seizures, speech and mental retardation.The result of gene test showed the mutation of SMC1A gene c. 2923C > T, and thus the patient was diagnosed as type 2 CdLs. Conclusions:CdLs is a rare genetic metabolic disease with special facial features and physical signs.There is only one case of CdLs with gene mutation of SMC1A in China through literature review.The mutation of SMC1A gene c. 2923C>T in CdLs cases has not been reported at home and abroad, which expands the variation spectrum of the SMC1A gene.

A Rare Case of Cornelia de Lange Syndrome Achieving Intracardiac Repair of Tetralogy of Fallot Following Ectopic Patent Ductus Arteriosus Banding / 日本心臓血管外科学会雑誌

We describe the case of a 1-year and 7-month-old girl who was born at 36 weeks and 6 days of pregnancy weighing 1,351 g. In addition to the diagnosis of Cornelia de Lange syndrome and Tetralogy of Fallot, we confirmed shunt blood flow from the lesser curvature of the aortic arch to the main pulmonary artery. Thus, we additionally diagnosed ectopic patent ductus arteriosus (PDA). Ultrasonography showed interruption and retrograde flow of the diastolic blood flow in the anterior cerebral artery. Therefore, we made a diagnosis of blood stealing due to an ectopic PDA, and we performed surgical intervention via a median sternotomy at 25 days. When we ligated the shunt blood vessel, the percutaneous oxygen saturation decreased from the high 90% range to the low 70% range, thus we temporarily released the ligation. We narrowed the ectopic PDA so that the percutaneous oxygen saturation could be maintained the high 80% range. Postoperative ultrasonography showed improvement of the pressure waveform in the anterior cerebral artery. After discharge, oxygen demand increased gradually with weight gain, and we performed intracardiac repair using a monocusp valve patch at 1 year and 7 months. We report a rare case of Cornelia de Lange syndrome wherein we achieved intracardiac repair of Tetralogy of Fallot after ectopic PDA banding in the neonatal period.

Disfagia orofaríngea em crianças com síndrome Cornélia De Lange: série de casos / Orofarineal dysfunction in children with the Cornélia De Lange Syndrome: series of cases / Disfagia orofaríngea en niños con síndrome de Cornelia De Lange: serie de casos

Introdução: A síndrome Cornélia De Lange (CdLS) é caracterizada por ser polimalformativa que envolve anomalias faciais, atraso de crescimento e desenvolvimento psicomotor, alterações comportamentais e malformações associadas. Sabe-se que as crianças acometidas por essa síndrome apresentam alterações de deglutição, mas são poucos os estudos apresentados na literatura devido à raridade da doença, sendo encontrado relato de um caso, e na maioria das vezes, com descrição dos achados. Objetivo: Identificar as alterações de deglutição em crianças com a Síndrome Cornélia de Lange, por meio da videofluoroscopia. Metodologia: Série de Casos, retrospectiva. Trata-se de uma amostra de conveniência com crianças, diagnosticadas com Síndrome Cornélia de Lange, que apresentassem videofluoroscopia da deglutição. Foram excluídos prontuários de pacientes que não estivessem completos. Os dados de caracterização da amostra foram obtidos através de prontuários físicos e os dados de desfecho do estudo através de laudos clínicos de videofluoroscopias da deglutição dos pacientes. Resultados: Dos 6 indivíduos, 5 do sexo masculino, em que 3 (50%) apresentaram aspiração laringotraqueal, de forma silente. A mediana de idade foi de 5,50 meses. Conforme os achados nas videofluoroscopias da deglutição, identificou-se dificuldades de deglutição como escape posterior prematuro de alimento, ejeção ineficiente e dificuldades de formação do bolo alimentar, como atraso no acionamento da reação faríngea, refluxo para nasofaringe, estase em valéculas e seios periformes e aspiração traqueal. Conclusão: Todas as crianças com Síndrome Cornélia de Lange deste estudo apresentaram disfagia em algum grau, e metade delas apresentou aspiração laringotraqueal de forma silente.

Introduction: Cornélia De Lange Syndrome (CdLS) is characterized by being polymalformative that involves facial anomalies, growth and psychomotor development retardation, behavioral changes and associated malformations. It is known that children affected by this syndrome have swallowing disorders, but there are few studies presented in the literature due to the rarity of the disease, with a case report being found and mostly with description of the findings. Objective: To identify swallowing disorders in children with Cornelia de Lange Syndrome, through videofluoroscopy. Methodology: Case series, retrospective. This is a convenience sample with children, diagnosed with Cornelia de Lange Syndrome, who had swallowing videofluoroscopy. Medical records of patients who were not complete were excluded. The sample characterization data were obtained from physical records and the study outcome data through clinical reports of patients' swallowing videofluoroscopies. Results: Of the 6 individuals, 5 were male, in which 3 (50%) had laryngotracheal aspiration, silently. The median age was 5.50 months. According to the findings in the swallowing videofluoroscopies, swallowing difficulties were identified, such as premature posterior escape of food, inefficient ejection and difficulties in the formation of the bolus, such as delay in triggering the pharyngeal reaction, reflux to the nasopharynx, stasis in the valleys and peripheral sinuses and tracheal aspiration. Conclusion: All children with Cornelia de Lange Syndrome in this study had dysphagia to some degree, and half of them had silent laryngotracheal aspiration.;Introducción: El síndrome de Cornélia De Lange (CdLS) se caracteriza por ser polimalformativo que involucra anomalías faciales, retraso del crecimiento y desarrollo psicomotor, cambios de comportamiento y malformaciones asociadas. Se sabe que los niños afectados por este síndrome presentan trastornos de la deglución, pero existen pocos estudios presentados en la literatura debido a la rareza de la enfermedad, encontrándose un reporte de caso y la mayoría de las veces con descripción de los hallazgos.

Objetivo: identificar los trastornos de la deglución en niños con síndrome de Cornelia de Lange, mediante videofluoroscopia. Metodología: Serie de casos, retrospectiva. Se trata de una muestra de conveniencia con niños, diagnosticados de Síndrome de Cornelia de Lange, que habían ingerido videofluoroscopia. Se excluyeron los registros médicos de los pacientes que no estaban completos. Los datos de caracterización de la muestra se obtuvieron de los registros médicos físicos y los datos de los resultados del estudio a través de informes clínicos de videofluoroscopias de deglución de los pacientes. Resultados: De los 6 individuos, 5 eran varones, de los cuales 3 (50%) tenían aspiración laringotraqueal, en silencio. La mediana de edad fue de 5,50 meses. De acuerdo con los hallazgos en las videofluoroscopias de deglución, se identificaron dificultades de deglución, como escape posterior prematuro de alimentos, eyección ineficiente y dificultades en la formación del bolo, como retraso en el desencadenamiento de la reacción faríngea, reflujo a la nasofaringe, estasis en los valles y senos periféricos y aspiración traqueal. Conclusión: Todos los niños con síndrome de Cornelia de Lange en este estudio tenían disfagia en algún grado y la mitad de ellos tenían aspiración laringotraqueal en silencio.

Identification and prenatal diagnosis of a novel NIPBL mutation underlying Cornelia De Lange syndrome / 中华医学遗传学杂志

Objective@#To explore the genetic basis for an infant featuring developmental delay, hand deformity and hypertonia of extremities.@*Methods@#Clinical data and peripheral blood samples of the proband and her parents were collected. Following DNA extraction, potential mutations were screened on an Ion PGM platform using a gene panel. Suspected mutation was verified by PCR and Sanger sequencing.@*Results@#A novel heterozygous nonsense mutation, c. 2521C>T(p.R841X), was identified in the NIPBL gene. The mutation may cause premature termination of translation of the adhesion protein loading factor at 841st amino acids. The same mutation was not found in her parents and 931 healthy controls, and was absent from public databases including ExAC and 1000G. Bioinformatic analysis suggested the mutation to be disease causing.@*Conclusion@#The c. 2521C>T (p.R841X) mutation of the NIPBL gene probably underlies the Cornelia De Lange syndrome in the infant. Prenatal diagnosis may be provided to this family upon their subsequent pregnancy.

Surgical treatment of esotropia and unilateral ptosis in a patient with Cornelia de Lange syndrome / 영남의대학술지

Cornelia de Lange syndrome (CdLS) is a rare multisystemic disorder that is characterized by mental retardation, prenatal and postnatal growth retardation, limb anomalies, and distinctive facial features, which include arched eyebrows that often meet in the middle (synophrys), long eyelashes, low-set ears, small and widely spaced teeth, and a small and upturned nose. Ophthalmic manifestations include long eyelashes, nasolacrimal duct obstruction, myopia, ptosis, and strabismus. There has been no report of surgical treatment for esotropia and unilateral ptosis in patients with CdLS in Korea. I report a patient with CdLS who underwent surgical treatment for esotropia and unilateral ptosis with a good surgical outcome.

A successful dental management in a child with Cornelia de Lange Syndrome: rare case of Cornelia de Lange Syndrome in child / O sucesso do manejo odontológico em criança com Síndrome Cornelia de Lange: um caso raro da Síndrome Cornelia de Lange em criança

Background: the Cornelia de Lange Syndrome (CDLs) is a rare and complex syndrome characterized, basically, by psychomotor retardation associated with a number of congenital malformations. Aims: this paper reports the case of an 11-year-old female child diagnosed with Cornelia de Lange Syndrome (CdLS) and her successful dental management. Case report: the patient had severe mental retardation, definite negative behavior and the clinical findings included oral and physical changes. The patient's oral hygiene was deficient with the presence of calculus and gingivitis, besides several active caries lesions in permanent and deciduous dental elements. The treatment consisted in guidance for caregivers about oral hygiene and diet, and the dental procedures were performed under general anesthesia. Currently, the patient is accompanied by monthly follow-ups. Conclusions: the lack of knowledge about oral hygiene and cariogenic diets was identified as a one of the reasons for the oral diseases present. Due to the need to care for the other more serious and complex health problems, the oral diseases had evolved faster than usual and thus were difficult to treat and maintain thereafter. Under such conditions, the dentist plays a key role within a multidisciplinary team. From the guidance and knowledge provided in the dental clinic, there was a significant improvement in the life quality of the child and her family

A family with X-linked Cornelia de Lange syndrome due to a novel SMC1A missense mutation identified by multi-gene panel sequencing

Cornelia de Lange syndrome (CdLS) is a rare, clinically and genetically heterogeneous, multi-system developmental disorder caused by mutations in genes that encode components of the cohesin complex. X-linked CdLS caused by an SMC1A mutation is an extremely rare disease characterized by phenotypes milder than those of classic CdLS. In the Republic of Korea, based on a literature review, one family with SMC1A-related CdLS with mild phenotypes has been genetically confirmed to date. In this study, we describe the clinical features of a Korean boy with a hemizygous novel missense mutation and his mother with a heterozygous mutation, i.e., c.2447G>A (p.Arg816His) in SMC1A, identified by multi-gene panel sequencing. The proband had a mild phenotype with typical facial features and his mother exhibited a mild, subclinical phenotype. This study expands the clinical spectrum of patients with X-linked CdLS caused by SMC1A variants. Moreover, these findings reinforce the notion that a dominant negative effect in a carrier female with a heterozygous mutation in SMC1A results in a phenotype milder than that in a male patient with the same mutation.

Successful difficult airway management using GlideScope video laryngoscope in a child with Cornelia de Lange Syndrome / 영남의대학술지

Management of airway in a child with Cornelia de Lange Syndrome (CdLS) should be given due consideration because most of them have the problems related to difficult airway. The GlideScope video laryngoscope can be attempted during routine intubation, however it is mostly used in case of difficulty. With adequate preoperative airway assessment, we used the pediatric video laryngoscope as useful alternative airway device in a child with CdLS and orotracheal intubation proceeded uneventfully.

Tratamiento rehabilitador a un paciente con síndrome de Cornelia de Lange / Rehabilitation Treatment to a Patient with Cornelia de Lange Syndrome

Se presentó un paciente de un año de edad con síndrome Cornelia de Lange, único recibido en el Servicio de Rehabilitación del Policlínico Docente René Vallejo Ortiz del municipio Manzanillo, provincia Granma, con signos evidentes de retraso del desarrollo psicomotor, remitido al servicio por su médico de familia cuando tenía seis meses de nacido. Para su tratamiento se emplearon técnicas específicas de la estimulación temprana, se lograron pequeños avances en su desarrollo motor y cognitivo, aunque no solo depende de la rehabilitación, sino también del entorno familiar en el cual se va desarrollando el niño. Se lograron pequeños avances motores en el paciente como: sostén cefálico, abertura de las manos y seguimiento de los objetos con la mirada, el paciente continúa rehabilitándose en el servicio de fisiatría.

A one -year-old patient with Cornelia de Lange syndrome (SCdL) was presented in this article, who was the only one attended in the service of rehabilitation of the René Vallejo Ortiz teaching polyclinic of Manzanillo municipality, Granma province. The patient had evident signs of late psychomotor development, so he was referred to this service by the family doctor when he was six months of age. For the treatment, specific techniques of early stimulation were used; small advances have been achieved regarding motor and cognitive development, although it not only depends on the rehabilitation, but also depends on the family environment, in which the infant is developing. Not many motors progresses were achieved in the patient such as: cephalic support, opening of the hands and objects pursuit followed by the eyes. The patient continues rehabilitating in the physiotherapy service.

Síndrome de Cornelia de Lange y deficiencias hormonales pituitáricas múltiples, una asociación inusual: Caso clínico / Cornelia de Lange Syndrome and multiple hormonal deficiency, an unusual association: Clinical case

El síndrome de Cornelia de Lange es una enfermedad genética caracterizada por rasgos faciales distintivos, falla de medro, microcefalia y varias malformaciones asociadas. Sus principales alteraciones endocrinológicas son las anomalías genitales. Se presenta un adolescente de 13 años, tratado por neumonía aspirativa complicada y que presentaba el fenotipo del síndrome de Cornelia de Lange, que incluía retraso global del desarrollo, trastorno de succión-deglución, talla baja y alteración del desarrollo sexual. Su edad ósea era muy retrasada, por lo que se realizó un estudio endocrinológico completo. Se le diagnosticaron hipotiroidismo central, deficiencia de la hormona de crecimiento y deficiencia de hormona luteotrópica y folículoestimulante, compatibles con el diagnóstico de deficiencias hormonales pituitáricas múltiples. Tuvo cortisol basal, hormona adrenocorticotrópica y prolactina normales. Recibió suplencia hormonal tiroidea. Es inusual la asociación de este síndrome con deficiencias hormonales pituitáricas múltiples. Se sugiere la evaluación de los distintos ejes endócrinos en estos pacientes.

Cornelia de Lange syndrome is a genetic disease characterized by distinctive facial features, failure to thrive, microcephaly and several malformations associated. Its main endocrinological features are anomalies of the genitalia. We present a 13-year-old boy, who suffered from complicated aspiration pneumonia and showed Cornelia de Lange syndrome phenotype, with global developmental delay, suction-swallowing abnormalities, short stature and abnormal genitalia associated. His bone age was delayed, so he underwent full endocrinological panel. Central hypothyroidism, growth hormone deficiency and low luteinizing hormone-follicle-stimulating hormone levels were observed and multiple pituitary hormone deficiencies diagnosis was made. Basal cortisol, adrenocorticotropic hormone and prolactin levels were normal. He received thyroid hormonal substitution. Multiple pituitary hormone deficiencies are an unusual feature of De Lange syndrome. We suggest evaluating all different endocrine axes in these patients.

Genetic analysis of Cornelia de Lange syndrome in one case / 临床儿科杂志

Objective To explore the clinical features and gene mutation types of Cornelia de Lange syndrome (CdLS), an inherited metabolic disease. Methods The clinical data and gene detection results of one case of CdLS were retrospectively analyzed. Results Two-year-old male had special appearance, microcephaly, bushy eyebrows with both sides meeting in the midline, long curly eyelashes, low body mass, and motor and mental retardation. NIPBL gene detection found the variation of the nucleotide in c.7176T>A (nucleotide 7176 in coding region changed from T to A). Conclusions CdLS is a rare congenital inherited metabolic disease. The clinical manifestations were special appearance and signs. The c.7176T>A mutation in NIPBL gene has not been reported at home and abroad.

Síndrome de Cornelia. Presentación de caso de enfermería vinculado a la teoría de Ida Orlando / Cornelia de Lange syndrome. Presentation of a case of nursery related with Ida Orlando theory

En 1933, una pediatra holandesa, la Dra. Cornelia de Lange, describía dos niños con rasgos similares, hoy en día es ella a quien se le reconoce el haber descrito los síntomas que abarcan el síndrome que lleva su nombre. Es un trastorno malformativo múltiple congénito, se determina por sus características faciales en asociación con retraso del crecimiento pre y postnatal, retraso mental de nivel variable, en algunos casos, anomalías de las partes superiores, muchos de los síntomas se pueden mostrar en el nacimiento y a muy temprana edad. El proceso de atención de enfermería, es el método científico de actuación de los profesionales de Enfermería, vinculado a una base teórica que desarrollan habilidades analíticas que aplicadas en la práctica, repercuten en la mejoría de los pacientes. Se realizó este trabajo con el objetivo de presentar un caso poco frecuente del síndrome de Cornelia de Lange, ejecutando el proceso de atención de Enfermería vinculado al modelo teórico de Ida Orlando. Se trató de una paciente de 10 meses de edad, sexo femenino, raza blanca, que ingresó a los dos meses de nacida en la sala de terapia intensiva del Hospital Pediátrico Provincial Eliseo Noel Caamaño, de Matanzas. La vinculación de la teoría de Ida Orlando a este proceso de atención de Enfermería permitió una atención integral al individuo enfermo, y desarrolló las habilidades prácticas de la asistencia de Enfermería, además de fomentar el razonamiento critico en aras de brindar cuidados con calidad y enfoque científico.

In 1933, a Dutch pediatrician, PhD Cornelia de Lange described two children with similar characteristics. Nowadays she is recognized as the one who described the symptoms encompassing the syndrome named after her. It is a congenital multiple malformative disorder, determined by its facial characteristics associated to pre and postnatal grow retardation, mental retardation of variable level, and, in some cases, anomalies of the upper parts. Many of the symptoms appear at birth and at early ages. The process of nursery care is the scientific method ruling Nursery professionals’ performance, related to a theoretical basis and developing analytical skills that, practically applied, strike on patients’ improvement. This work was carried out with the aim of presenting a few frequent case of Cornelia de Lange Syndrome, performing the Nursery care process according to Ida Orlando theoretical model. It deals with female, white, 10-months patient who entered the Intensive Care Service of the Provincial Pediatric Hospital “Eliseo Noel Caamaño”, of Matanzas when she was two months. Relating Ida Rolando’s theory to this Nursery care process allowed the patient’s integral care, and developed the practical skills of Nursery care, besides promoting the critical reasoning for the sake giving a quality and scientifically focused care.

Progress in cornelia de lange syndrome / 国际儿科学杂志

Cornelia de Lange syndrome is a rare congenital disease,which was firstly reported on 1933.It usually causes multiple organs dysplasia.Clinical manifestations include severe growth retardation,cogni-tive impairment,characteristic facial and upper limb defects.With the rapid development of medical science,es-pecially in genetics and molecular biology,much research on the pathogenesis of Cornelia De Lange syndrome has been performed.Herein,we review the progress in this rare disease in recent years.

Cornelia De- Lange Syndrome: A Case Report.

Cornelia de Lange syndrome (CDLS) is a congenital disorder involving skeletal, craniofacial deformities together with gastrointestinal and cardiac malformations. Here with, dental management of a case with CDLS syndrome is described.

Novel Pathogenic Variant (c.3178G>A) in the SMC1A Gene in a Family With Cornelia de Lange Syndrome Identified by Exome Sequencing

Cornelia de Lange syndrome (CdLS) is a clinically and genetically heterogeneous congenital anomaly. Mutations in the NIPBL gene account for a half of the affected individuals. We describe a family with CdLS carrying a novel pathogenic variant of the SMC1A gene identified by exome sequencing. The proband was a 3-yr-old boy presenting with a developmental delay. He had distinctive facial features without major structural anomalies and tested negative for the NIPBL gene. His younger sister, mother, and maternal grandmother presented with mild mental retardation. By exome sequencing of the proband, a novel SMC1A variant, c.3178G>A, was identified, which was expected to cause an amino acid substitution (p.Glu1060Lys) in the highly conserved coiled-coil domain of the SMC1A protein. Sanger sequencing confirmed that the three female relatives with mental retardation also carry this variant. Our results reveal that SMC1A gene defects are associated with milder phenotypes of CdLS. Furthermore, we showed that exome sequencing could be a useful tool to identify pathogenic variants in patients with CdLS.

Frenectomia labial em paciente com síndrome de Cornelia de Lange / Labial frenectomy in patient with Cornelia de Lange syndrome

Síndrome de Cornelia de Lange é uma anormalidade de desenvolvimento multisistêmica caracterizada por retardo cognitivo e de crescimento; dismorfia craniofacial, malformações dos membros superiores; disfunção geniturinária e oftalmológica, hirsutismo e anomalias cardíacas e gastroesofágicas. Cílios longos e sobrancelhas arqueadas com sinófiris, filtro longo com lábio superior fino. Ponte nasal deprimida com narinas antevertidas também ocorre com frequência. Problemas dentários são frequentes e incluem: palato ogival, micrognatia, atraso na erupção, erosão dental, doença gengival e periodontal. Com base nessas observações, o presente estudo tem como objetivo descrever a frenectomia labial em um paciente com síndrome de Cornelia de Lange, de 19 anos de idade, gênero masculino, bem como as recomendações para o manejo clínico e controle do biofilme dental

Cornelia de Lange syndrome is an abnormality multisystem developmental characterized by cognitive and growth retardation; craniofacial dysmorphia, malformations of the upper extremities, genitourinary and ophthalmologic dysfunction, hirsutism, cardiac and gastroesophageal abnomalies. Long eyelashes, arched eyebrows with synophrys, long philtrum with thin upperlip. Depressed nasal bridge with anteverted nares also frequently occur. Dental problems are common and include: high palate, micrognathia, delayed eruption, dental erosion, gingival and periodontal disease. Based on these observations, the present study aims to describe the labial frenectomy in a patient with Cornelia de Lange syndrome, 19 years old, male gender, as well as recommendations for the clinical management and control of dental biofilm

Síndrome Cornelia de Lange: reporte de un caso / Cornelia de Lange syndrome: a case report

INTRODUCCIÓN: El Síndrome Cornelia de Lange (SCdL), es un trastorno congénito del desarrollo, se presenta en descendencia de padres consanguíneos. Prevalencia de 0,2 a 1 por 10.000 nacidos vivos. Existe evidencia de cromosomopatías 3q25-29 y 5p13-14. Presenta un fenotipo facial característico con microcefalia, sinofridia, pestañas largas, labios en V-invertida, además de hipertricosis, oligodactilia, retraso del desarrollo psicomotor, y cardiopatías. El objetivo es establecer los antecedentes médicos relevantes para diagnosticar de forma precoz la enfermedad. CASO CLÍNICO: Niña de 16 meses de edad, padres consanguíneos, nacida prematura de 36 semanas, se le diagnostica un SCdL grave, además tiene cardiopatía congénita, riñones poliquísticos, hipoacusia severa, reflujo gastroesofágico complicándose con neumonía por aspiración. DISCUSIÓN: El diagnóstico se realiza con examen físico y cariograma. Considerar el Síndrome Alcohólico Fetal como diagnóstico diferencial. Para el tratamiento, es fundamental seguir las pautas del 2007 para el manejo de individuos con SCdL, así prevenir complicaciones respiratorias.

INTRODUCTION: Cornelia de Lange Syndrome (CdLS), is a congenital developmental disorder, occurs in offspring of consanguineous parents. The prevalence is 0.2 to 1 per 10,000 live births. There are evidence of chromosomopathies 3q25-29 and5p13-14. The affected have a characteristic facial phenotype with microcephaly, synophrys, long eyelashes, V-shaped invertedlips, hypertrichosis, oligodactyly, psychomotor retardation, and heart disease. The aim is to establish the relevant medical background for early diagnosis of the disease. CASE REPORT: Girl, 16 months old, consanguineous parents, born 36 weeks premature, diagnosed with a severe CdLS, congenital heart disease, polycystic kidneys, severe bilateral hearing loss, gastroesophageal reflux complicated by aspiration pneumonia. DISCUSSION: The diagnosis of CdLS is made by physical exam and karyotype. Fetal Alcohol Syndrome is the differential diagnosis. For treatment, it is essential to follow the 2007's guidelines for the management of individuals with CdLS and prevent respiratory complications.