Cornelia de Lange syndrome (CdLS) is a congenital multisystemic genetic disorder. The expected lifespan of children with this disorder has been prolonged in parallel with the advances in medicine in recent years. However, they still more frequently undergo cardiac surgery. There are some challenges for clinicians when faced with CdLS patients. We present the perioperative management of a child with CdLS undergoing open-heart surgery.

Severe pulmonic and subpulmonic valvular stenosis, enlargement of the right side of the heart, mild tricuspid regurgitation, atrial septal defect, and patent ductus arteriosus were diagnosed in a 14-month-old boy with manifested cyanosis, developmental delay, and malnutrition. Attempted balloon valvuloplasty was unsuccessful due to a severe stenotic pulmonary valve, therefore it was decided to perform an open surgical repair. Following a successful and uncomplicated intraoperative course, the patient was extubated on postoperative day 5, and adrenalin and dopamine infusions were gradually decreased and stopped on postoperative days 6 and 10, respectively. Moderate laryngomalacia and suboptimal vocal cord movements were diagnosed, and tracheotomy and percutaneous endoscopic gastrostomy were performed under general anesthesia in the same session at postoperative day 32. The patient was discharged on postoperative day 85 after a challenging postoperative period with additional airway and nutritional problems.

This is the first report of the perioperative anesthetic and clinical management of a CdLS patient undergoing open-heart surgery.

Cornelia de Lange syndrome Spectrum (CdLSp) is characterized by intellectual disability, facial dysmorphisms, and growth impairment. Although eating difficulties are a well-known feature of the disease, there is no data regarding the nutritional deficiencies of these patients. The food intake was tracked using a dietary transcription provided by the family/caregivers, biochemical nutritional parameters were measured with laboratory tests and through an accurate clinical evaluation of the incidence of qualitative and quantitative imbalances in a cohort of 73 patients with CdLSp ware determined. Of these 73, 62 (85%) subjects provided a complete and detailed dietary transcription. In the studied population, a quantitative caloric imbalance in 47/62 (76%) subjects was observed. The caloric intake was low in 27/62 (43%) subjects whereas excessive in 20/62 (33%). Only 15/62 (24%) had an optimum caloric intake. Regarding micronutrients, a calcium intake deficiency in 32% of the patients (20/62) was observed. Blood tests revealed a low iron level in 22/73 (30%) of the patients and 25(OH)D deficiency in 49/73 (67%). Serum hypocalcemia was not evidenced. Qualitative and quantitative imbalances resulted in more frequent than expected in CdLSp patients. A qualitative imbalance was more prevalent in younger patients while in older patients prevailed mainly a quantitative disproportion. We found no statistically meaningful correlation between dietary imbalances, genetic, or clinical parameters. Our findings highlight the need for further studies to evaluate the basal metabolic rate of CdLSp patients and find a correlation with their growth impairment.

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning.

Cornelia de Lange syndrome is a dominantly inherited, genetically heterogeneous and clinically variable syndrome with multiple congenital anomalies and developmental delay. Gastrointestinal anomalies are common and an important cause of morbidity and mortality. We report on a newborn with a molecularly confirmed Cornelia de Lange syndrome who had an imperforate anus. This is the third report of Cornelia de Lange syndrome and imperforate anus.

Cornelia de Lange syndrome is a syndrome of multiple congenital anomalies. The genetic and molecular bases of these lesions are not clear. It is divided into three types based on the severity of the anomaly. Dental findings revealed contracted maxilla, malaligned teeth, multiple impacted and missing teeth. This article describes the successful management of upper central incisor with lateral opening in the apical third on the mesial surface of the root along with aesthetic and functional rehabilitation.

The aim of this study was to describe the experience of 452 children and adults with a severe developmental disability who presented to a multidisciplinary clinic with swallowing, nutritional, and gastrointestinal problems. Data were obtained by chart review. Two hundred and ninety-four children (age range 7 mo-19 y, 173 males, 121 females) and 158 adults (age range 18-53 y; 90 males, 68 females) were assessed over 5 years. One hundred and eighty-two children and 86 adults had cerebral palsy. Approximately 90% were wheelchair dependent and totally dependent on caregivers for feeding; 60% had epilepsy. Pulmonary aspiration was identified by oesophageal videofluoroscopy in 41% of 174 children and 47% of 34 adults. Chronic oesophagitis and Helicobacter pylori were found in 57% of 182 children and 76% of 66 adults undergoing endoscopy. Chronic suppurative lung disease was identified by computerized axial tomography in 94% of 62 children and all six adults studied. Most patients improved with simple interventions. However, gastrostomy was recommended in 140 children and performed in 91, and in 10 adults but performed in seven, whereas fundoplication was recommended in 111 children and performed in 74, and in six adults but performed in two. In conclusion, chronic oesophagitis, pulmonary aspiration, and chronic lung disease were identified in many patients with a severe developmental disability.

Cornelia de Lange syndrome is a rare congenital disorder. Symptoms include a characteristic facial structure, pre- and post-natal growth deficiency, hypertrichosis, and visceral and cardiovascular anomalies. Behavioural problems and moderate to severe mental retardation are also present. In this paper, we report a mild case of Cornelia de Lange syndrome. The neuropsychological rehabilitation of this patient is also described. It was structured on the patient's specific areas of strength and weakness in order to facilitate the development of adaptive cognitive abilities. To maximise the learning potential of these children, we recommend specific interventions with a multidimensional neuropsychological approach, which considers developmental abilities and disabilities as related to the global reality of the child.

There has been limited empirical research into the environmental causes of self-injury in Cornelia de Lange syndrome. The present study examined the variability of self-injurious behaviour in Cornelia de Lange syndrome across environmental setting events. Additionally, the association between setting events and more specific environmental events was examined.

A descriptive analysis of observational data on eight children with Cornelia de Lange syndrome aged between 4 and 14 years was carried out. The association between self-injurious behaviour and four environmental setting events and between specific environmental events and setting events was examined using established statistical methods for observational data.

Seven out of eight of the participants showed at least one form of self-injurious behaviour that was associated with a particular setting event. The study also demonstrated that the relationship between setting events and environmental events is extremely variable across individuals.

Self-injurious behaviour in some individuals with Cornelia de Lange syndrome is associated with environmental events although the precise nature of the association warrants clarification. Using broad setting events as a methodological tool in isolation provides some insight into the role of specific environmental factors in maintaining self-injurious behaviour but the integrity of setting events must be established.

As previously reported, gastroesophageal reflux (GER) is a frequent and severe medical complication of Cornelia de Lange syndrome (CDLS). The incidence of GER and the correlation between its presence and degree, and the clinical phenotype of CDLS (mild/classical according to Van Allen classification) were evaluated in a series of 43 patients. The pattern of presenting symptoms and their clinical evolution after medical or surgical treatment were also studied. A pathological GER was evident in 28/43 (65%) CDLS patients. The incidence of the complication was not significantly different in patients with classical (93.3%) vs. mild phenotype (82.3%), whereas a strong correlation was present between the degree of the esophageal damage and the clinical phenotype. A behavioral symptom (hyperactivity) was the most frequent sign associated with the condition (85%). Our data confirm the high occurrence of GER in CDLS patients, independently from the CDLS clinical phenotype. Regarding the severity of the esophageal lesions, a significant difference between the two clinical CDLS phenotypes was found. The evaluation of the presenting symptoms and of their evolution during the treatment emphasizes the importance of behavioral symptoms as major signs of esophageal damage in CDLS.

The developing fetal upper aerodigestive system provides the structural support for respiratory and ingestive functions necessary to sustain life at birth. This study investigated prenatal development of upper aerodigestive anatomy and the association of emerging functions as predictors of postnatal feeding skills. Biometric measures of oral, lingual, pharyngeal and laryngeal structures were obtained in fetuses 15-38 weeks gestational age using a four-plane sonographic technique. Accompanying ingestive behaviors were tallied across development. The data from 62 healthy controls were compared to seven cases at risk for postnatal feeding and swallowing dysfunction (Type II Arnold Chiari Malformation, trisomy 18, polyhydramnios, intrauterine growth restriction, Brachmann-de Lange Syndrome). Significant (p<0.001) linear regressions occurred in pharyngeal and lingual growth across gestation while ingestive behavior such as suckling emerged in a sequence of basic to complex movement patterns. Jaw and lip movements progressed from simple mouth opening to repetitive open-close movements important for postnatal suckling. Lingual movements increased in complexity from simple forward thrusting and cupping to anterior-posterior motions necessary for successful suckling at term. Laryngeal movements varied from shallow flutter-like movements along the lumen to more complex and complete adduction-abduction patterns. Fetal swallowing primarily occurred in the presence of concomitant oral-facial stimulatory activity. Significant variations (p<0.01) in the form and function of the ingestive system occurred in comparisons of gestational age-matched controls to at-risk cases. We postulate that prenatal developmental indices of emerging aerodigestive skills may guide postnatal decisions for feeding readiness and, ultimately, advance the care of the premature, medically fragile neonate.

Our investigation of fetal swallowing has identified potential limitations in the use of color Doppler imaging for detection of amniotic fluid flow and discrimination of respiratory from ingestive activity. The objective of this study was to evaluate an alternative imaging modality, power Doppler sonography, as a technique to enhance detection of amniotic fluid flow in the upper aerodigestive tract.

We applied a standardized 4-axis sonographic examination of upper aerodigestive structures and used power Doppler imaging to document amniotic fluid flow. Normal aerodigestive activities from 62 healthy control subjects were compared with 4 abnormal cases.

Our longitudinal experience with 66 subjects showed that a directed evaluation of the fetal upper aerodigestive tract with power Doppler imaging provided a systematic approach for studying the physiologic development of this region in both healthy and at-risk fetuses.

A standardized 4-axis examination with power Doppler imaging is a useful adjunct in addressing ingestive and respiratory functions in the developing fetus.

Cornelia-de-Lange syndrome is a dysmorphogenic disorder characterized by multiple congenital abnormalities, and in most cases, severe cognitive limitations. Parents of 27 children with Cornelia-de-Lange syndrome completed psychological questionnaires concerning communicative and social-emotional behaviours, and reported on their parenting stress. Only four children were able to use speech, but most of the older children expressed needs through non-verbal means. Feeding problems, over-activity, irritability and stereotyped behaviours were characteristic for the majority of the group. Self-injurious behaviours occur in more than 40%. Parenting stress is very high, especially in parents of older children.

Seven patients, including two sibs, with the Brachmann-de Lange syndrome (BDLS) are presented as representative of the different types of BDLS in a proposed classification system. Type I ("classic") patients have the characteristic facial and skeletal changes of BDLS using the criteria in the diagnostic index of Preus and Rex. Type I is distinguished from the other subtypes by prenatal growth deficiency (< 2.5 S.D. below mean for gestation) becoming more severe postnatally (< 3.5 S.D. below the mean), moderate to profound psychomotor retardation, and major malformations which result in severe disability or death. Type II ("mild") BDLS patients have similar facial and minor skeletal abnormalities to those seen in type I; however, these changes may develop with time or may be partially expressed. Patients with type II BDLS are distinguished from those with other types by mild to borderline psychomotor retardation, less severe pre- and postnatal growth deficiency, and the absence of (or loss severe) major malformations. Behavioral problems can be a significant clinical problem in type II BDLS. Type III ("phenocopies") BDLS includes patients who have phenotypic manifestations of BDLS which are causally related to chromosomal aneuploidies or teratogenic exposures.