Nissen fundoplication in Cornelia de Lange syndrome spectrum: Who are the potential candidates?

Cornelia de Lange spectrum (CdLSp) is a rare genetic condition characterized by intellectual disability, facial dysmorphisms, major malformations, growth impairment, and development delay. Approximately 80% of CdLSp patients have gastroesophageal reflux disease (GERD) with a varied clinical presentation. The aim of this study is to define potential clinical/genetic risk factors based on the clinical phenotype description of CdLSp patients with severe GERD who underwent surgical treatment. We retrospectively collected data from 23 CdLSp patients, 13 females and 10 males. Mean age of the patients undergoing surgical treatment was of 4 years. 21/23 (91%) had a molecular characterization, of which 21/21 (100%) had a NIPBL gene mutation, while 2/23 (9%) did not have a genetical characterization, only a clinical diagnosis. Most of our patients presented a moderate-severe severity score (21/23, 91%) with limb malformations evidenced in 10/23 (44%) of our patients and a moderate-severe intellectual disability in 20/23 (87%). Therefore, CdLSp patients harboring NIPBL variants, upper limb malformations and severe psychomotor delay are more likely to suffer from severe GERD, not responsive to proton pump inhibitors treatment. These features should be considered as clinical markers for potentially severe GERD that might require surgical treatment.

Endometrial Carcinoma With an Unusual Morphology in a Patient With Cornelia de Lange Syndrome: A Case Study.

Cornelia de Lange syndrome (CdLS) is a cohesinopathy, which is characterized by multiple structural anomalies as well as mental and growth retardation. A 36-yr-old nulliparous woman with oligomenorrhea was referred to us due to a mass in the uterine corpus. She had been clinically diagnosed with CdLS during infancy based on her specific facial features as well as growth and intellectual retardation. Imaging examinations and an endometrial biopsy revealed endometrial endometrioid carcinoma and polycystic ovary syndrome (PCOS). She underwent a hysterectomy and bilateral salpingo-oophorectomy. The tumor was mainly located at the uterine isthmus and exhibited diffuse exophytic growth. Microscopically, the grade 1 endometrioid carcinoma consisted of extremely well-differentiated glands and showed myometrial invasion. Both swollen ovaries had a thick fibrous cortex and multiple follicles. To the best of our knowledge, this is the first case report of a gynecologic malignancy in an adult patient with CdLS. Several gene mutations have been reported to be causative of CdLS; however, a potential role of these mutations in the pathogenesis of PCOS and subsequent endometrial cancer remains controversial. In this case, PCOS seemed to underlie the endometrial carcinogenesis and then concurrent loss of PTEN and PAX2 expression, confirmed by immunohistochemistry, can facilitate tumor progression. Our case suggests that adult female patients with CdLS can have PCOS and subsequent endometrial carcinoma. As patients with CdLS often have difficulties recognizing and/or reporting menstrual disorder, their care providers should pay particular attention to menstrual cycle irregularities due to the risk of endometrial cancer.

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(AU)

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 Rolandos theory to this Nursery care process allowed the patients 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(AU)

Ventilation tube insertion is not effective to the treatment of hearing impairment in pediatric patients with Cornelia de Lange syndrome.

OBJECTIVE: Cornelia de Lange syndrome (CdLS) is a multiple developmental disorder including hearing loss. The hearing impairment in CdLS patients is not only sensorineural but also conductive hearing loss (CHL). The aim of this study was to elucidate hearing loss causes in CdLS patients and evaluate the effect of ventilation tube (v-tube) insertion in the cases of CHL. METHODS: Thirty-two patients clinically diagnosed with CdLS were enrolled and analyzed with retrospective case review. Audiologic evaluations and imaging studies such as a temporal bone computed tomogram or brain magnetic resonance imaging (MRI) were performed for all patients. Hearing rehabilitation such as ventilation tube insertion, hearing aid fitting, or cochlear implantation was chosen depending on the audiological condition. RESULTS: Among 32 CdLS patients who underwent auditory brainstem response test, 81.2% presented hearing loss. Imaging studies showed that only middle ear lesions without inner ear anomalies were identified in 56.3%. Notably, the soft tissue lesion in middle ear was identified even in the neonatal MRI. When 7 patients were thought to have CHL due to otitis media with effusion, v-tube insertion was applied first. However, v-tube insertion rarely improved CHL postoperatively. Moreover, middle ear lesion was not fluid effusion but soft tissue lesion according to the intraoperative finding. These lesions were not eradicated even after revision surgery of v-tube insertion. CONCLUSION: V-tube insertion is not effective to improve hearing or eradicate otitis media with effusion in CdLS patients.

Brachmann-Cornelia de Lange syndrome with a papilloma of the choroid plexus: analyses of molecular genetic characteristics of the patient and the tumor. A single-case study.

PURPOSE: A 10-month-old girl with a Brachmann-Cornelia de Lange syndrome and a choroid plexus papilloma of the brain was studied at the Hospital Infantil de México Federico Gómez (HIMFG) in Mexico City. METHODS AND RESULTS: Presumptive papilloma of the third ventricle was evidenced on CT and MR images and removed. Pathological analysis confirmed its origin. A posterior radiosurgery was required due to a tumor relapse. Karyotypes (GTG bands) of the patient and her parents undertaken at HIMFG were normal. Array comparative genomic hybridization (array CGH) analyses of blood DNA of the patient and her parents carried out at BlueGnome's Laboratory in Cambridge, UK, set in evidence amplification of genes SPNS2, GGT6, SMTNL2, PELP1, MYBBP1A, and ALOX15 in chromosome 17p of the patient. Since MYBBP1A is a proto-oncogene and ALOX15 participates in the development of cancer and metastases of tumors, further fluorescent in situ hybridization (FISH) analyses of these two genes were implemented at HIMFG. Amplification of the two genes was found in the tumor of the case under study but not in an unrelated papilloma of the choroid plexus. DISCUSSION: Further analyses of the association of choroid plexus papillomas with disorders of psycho-neural development and its relationship to molecular genetic modifications at chromosome 17p are now under way at HIMFG.

Unpredictable drug reaction in a child with Cornelia de Lange syndrome.

CASE DESCRIPTION: Preoperative use of midazolam sedation is mandatory during induction of anesthesia in noncooperative and hyperactive children to prevent possible obstacles. Unusual drug reactions rarely occur in patients undergoing anesthesia or in intensive care unit. This report describes an unpredictable drug reaction after a routine midazolam premedication in a patient with no history of allergy. There has been no literature data yet to show that midazolam can provoke respiratory problems in patients with Cornelia de Lange Syndrome. CONCLUSION: In our opinion midazolam should be avoided in patients with Cornelia de Lange Syndrome, which we enforced after first unpredictable reaction.

Otolaryngological presentations of Cornelia de Lange syndrome.

AIM: Children with Cornelia de Lange syndrome frequently present to otolaryngology services with hearing problems. Airway problems have not previously been reported. We wish to describe our experience of the overall management in a series of children with Cornelia de Lange syndrome. METHODS: Retrospective case note review of children diagnosed with Cornelia de Lange syndrome presenting to our department between 2005 and 2014. RESULTS: Six patients were seen. Airway problems consisted of laryngeal overspill with severe gastroesophageal dysmotility and reflux despite structurally normal airway (1 case), laryngomalacia requiring supraglottoplasty (2 cases), reflux laryngitis with secondary laryngomalacia and coincidental tracheal diverticulum (1 case) choanal atresia requiring stents (1 case) and obstructive sleep apnoea (1 case). Supraglottoplasty produced a dramatic improvement in feeding and breathing in both children who underwent the procedure. Two children had palatal anomalies and one underwent cochlear implantation for a profound sensorineural hearing loss. CONCLUSION: Children with Cornelia de Lange syndrome have multifaceted ENT problems. Airway pathology has not previously been described in Cornelia de Lange syndrome but has been common in our experience. We wish to highlight that laryngomalacia in Cornelia de Lange syndrome responds well to supraglottoplasty.

Anestesia general combinada con analgesia epidural para ureteroneocistostomía en un paciente con síndrome de Cornelia de Lange / General anaesthesia combined with epidural analgesia for ureteroneocystostomy in a patient with Cornelia de Lange syndrome

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Post-operative respiratory complications after palatoplasty in a 19-month-old female with Cornelia de Lange syndrome--a case report.

Cornelia De Lange syndrome is a rare genetically heterogeneous and sporadic syndrome, with an estimated prevalence of 1 in 10,000 to 30,000. The disorder may present many complications during anesthesia due to cardiac, gastrointestinal and airway anomalies. We report a case of an ex premature toddler presenting for repair of a cleft palate. Postoperatively she had respiratory distress, successfully treated by the anesthetic care team Causes for the complication are discussed.

Spinal anesthesia in a child with Brachmann-de Lange (Cornelia de Lange) syndrome.

Providing anesthesia to patients with Brachmann-de Lange syndrome (BdLS) may be challenging, mainly because of intubation difficulty, gastroesophageal reflux disease, and aspiration complications. The use of spinal anesthesia (SA) in this population has not been reported. We report the uneventful administration of awake SA to a 7-month-old girl with BdLS who was scheduled for rectal biopsy. The current literature is reviewed to discuss the indications for SA in those patients.

Anesthetic management of an adult patient with Cornelia de Lange Syndrome.

Cornelia de Lange Syndrome is a well-known congenital disease characterized by multiple malformations that make anesthetic management a challenge. Since few individuals survive the earliest stage of life, papers describing the details of anesthetic management are mainly reported in the pediatric population. These individuals who move into adulthood develop physical changes that should be taken into consideration. This article reports the case of a 34-year-old patient undergoing an orthopedic procedure. The operation was performed under general anesthesia because the patient showed severe scoliosis and joint contractures, so extraordinary difficulty in neuroaxial and peripheral techniques was expected. The aggressive behavior of the patient impeded the proper assessment of a preoperative airway. Fiber optic intubation was performed under slight sedation after three unsuccessful attempts. Dental crowding, prominent upper central incisors that were more pronounced than in most children, a short and stiff neck, and poor patient cooperation due to mental retardation and occasional autistic behavior made airway management difficult. This case should alert anesthesiologists to the greater difficulties of managing patients with Cornelia de Lange Syndrome when they become adults.

Embolia gaseosa durante cirugía laparoscópica en lactante con síndrome de Cornelia de Lange / Air embolism during laparoscopic surgery in an infant girl with Cornelia de Lange syndrome

El síndrome de Cornelia de Lange es un cuadro polimalfomativopoco frecuente, con características fenotípicasparticulares (alteraciones craneofaciales comomicrocefalia o hipertricosis con sinofridia; alteracionescutáneas como hirsutismo; anomalías de las extremidades),asociado en un alto porcentaje a retraso mental yotro tipo de anomalías (digestivas, cardiacas, endocrinas).Presentamos el caso de una paciente de 2 meses deedad en la que se realizó por vía laparoscópica, una plastiaantirreflujo, cierre de defecto diafragmático y gastrostomía.Como antecedentes a destacar neumoníasaspirativas de repetición e hipertensión arterial. Duranteel inicio de la intervención quirúrgica, hubo dos episodiosde desaturación brusca, hipotensión y bradicardia,con diagnóstico probable de embolia aérea, que seresolvieron aplicando tratamiento específico. El manejoanestésico en estos pacientes para cirugía laparoscópicaes realmente complejo, por lo que hay que conocer demanera profunda la patología y complicaciones que puedansurgir(AU)

Cornelia de Lange syndrome involves multiplemalformations with particular phenotypic features(craniofacial abnormalities such as microcephaly orhypertrichosis with synophrys; cutaneous abnormalitiessuch as hirsutism, and limb anomalies) and it isassociated with a high percentage of mental retardationand complications such as digestive tract abnormalities,cardiac defects, and endocrine disorders. We report thecase of a 2-month-old infant girl who underwent alaparoscopic antireflux procedure, with closure of adiaphragmatic hernia and a gastric stoma. The medicalhistory included repeated episodes of aspirationpneumonia and hypertension. Early in the procedure, 2episodes of sudden desaturation, hypotension, andbradycardia with a probable diagnosis of air embolism.The complications resolved with specific treatment.Anesthetic management for laparoscopic surgery in thesepatients is truly complex and must be informed by athorough understanding of the disease and complicationsthat may develop(AU)

[Anesthetic management in a patient with Cornelia de Lange syndrome].

An eight-year-old boy with Cornelia de Lange syndrome underwent left inguinal hernioplasty and orchiopexy under general anesthesia. The patient with Cornelia de Lange syndrome had severe primordial growth failure with muscle-skeletal system such as cleft palate, micrognathia, and micromelia of the extremities and mental retardation as well as characteristic faces such as deep supercilia, etc. We suspected difficulty of endotracheal intubation due to this syndrome. Anesthesia was induced with intravenous injection of atropine 0.1 mg and ketamine 10 mg followed by inhalation of nitrous oxide 3 l x min(-1), oxygen 3 l x min(-1), and sevoflurane 5% without any muscle relaxant. Although his neck and temporomandibular joint were stiff, his trachea was intubated orally without difficulty with a 4.5 mm ID tracheal tube using a Macintosh laryngoscope. Anesthesia was maintained uneventfully by bolus intravenous injection of ketamine 5 mg and inhalation of oxygen and sevoflurane 2-3% with mechanical ventilation. The anesthetic management in a patient with Cornelia de Lange syndrome should be carried out with careful preoperative evaluation of physical status, and especially the difficult endotracheal intubation should be kept in mind. Induction of general anesthesia with injection of ketamine followed by inhalation of sevoflurane without muscle relaxant is a safe method in Cornelia de Lange syndrome.

[General anesthesia for a patient with Cornelia de Lange syndrome].

Cornelia de Lange syndrome involves anomalies in cardio-vascular and musculo-skeletal systems, and mental retardation. In addition, a patient with this syndrome shows a peculiar look. A 22-year-old woman with Cornelia de Lange syndrome underwent general anesthesia twice. She has a small mouth, thin lips, a short neck, short limbs, and stiffness of the neck and some joints associated with slight mental retardation. She was scheduled for arthroscopy and then for rotational acetabular osteotomy and valgus osteotomy. The maximum distance between the upper and lower incisors was 34 mm, when she opened her mouth. Anesthesia was induced with sevoflurane increased slowly to 7.0% in oxygen 6 l.min-1 in both procedures. After the administration of 4% lidocaine 3.5 ml into the pharynx, orotracheal intubation was attempted, but was not successful. Then blind naso-tracheal intubation was performed successfully under spontaneous respiration under sevoflurane-oxygen inhalation. The induction of anesthesia with sevoflurane under spontaneous respiration was useful for blind naso-tracheal intubation in a case with difficult intubation such as in Cornelia de Lange syndrome.