Nasal polyposis in pediatric patients with Cornelia de Lange syndrome: endoscopic diagnosis, treatment and follow up in two case reports.

BACKGROUND: Cornelia de Lange syndrome is a rare genetic disease with otolaryngological involvement. The classic phenotype is characterized by distinctive facial features, intellectual disability, growth delay, hirsutism, and upper-limb reduction. Nasal polyposis was previously reported in association with chronic rhinosinusitis, however data about prevalence, diagnosis, treatment and prognosis are lacking for this cohort of patients, affected by rare disease. CASE PRESENTATION: We describe the whole diagnostic and therapeutic workflow of nasal polyps in two pediatric patients with Cornelia de Lange, successfully diagnosed and treated by nasal endoscopy. CONCLUSION: Our report confirm that nasal endoscopy is a safe and useful tool in the diagnosis, treatment and follow-up of nasal polyps, even in Cornelia de Lange syndrome pediatric patients. We want to increase the alert for the detection of nasal polyps in patients with Cornelia de Lange syndrome since pediatric age. We recommend endoscopy in all patients with Cornelia de Lange syndrome and symptoms of chronic nasal obstruction and/or OSAS. Multidisciplinary team and sedation service could be useful in the management of Cornelia de Lange syndrome patients with airway obstruction symptoms and sleep disturbance when severe intellectual disability, autism or psychiatric findings are present.

Coats' Disease in a Patient With Cornelia de Lange Syndrome: Management With Laser and Bevacizumab.

Cornelia de Lange syndrome is a congenital disorder with multisystem abnormalities including multiple ocular findings. The authors report a case of Coats' disease in a patient with Cornelia de Lange syndrome who was successfully treated with laser and intravitreal bevacizumab. This case demonstrates the importance of fluorescein angiography in making the diagnosis and directing treatment and the efficacy of combined laser with intravitreal anti-vascular endothelial growth factor therapy for persistent vascular leakage associated with Coats' disease in Cornelia de Lange syndrome. [J Pediatr Ophthalmol Strabismus. 2023;60(4):e45-e48.].

Divergent presentation of anxiety in high-risk groups within the intellectual disability population.

BACKGROUND: Anxiety symptomatology is common in individuals with intellectual disability (ID). Symptomatology includes both traditional Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) anxiety disorders and autism spectrum disorder (ASD)-related anxiety traits. Some genetic disorders such as Cornelia de Lange (CdLS) and fragile X syndromes (FXS) are at very high risk of anxiety and afford the opportunity to examine prevalence, profiles and associated person characteristics. However, prevalence and associated characteristics of anxiety in these high-risk groups remain poorly described and understood. The aim of the current study was to examine the prevalence and profile of DSM-5 and ASD-related anxiety symptomatology in individuals with CdLS and FXS and associated behavioural and cognitive characteristics. METHODS: Questionnaires and interviews assessing DSM-5 and ASD-related anxiety were conducted with caregivers of individuals with CdLS (n = 49) and FXS (n = 36). RESULTS: DSM-5 anxiety symptomatology was present in both groups with high co-morbidity across anxiety diagnoses. ASD-related anxiety was also prevalent with specific difficulties related to intolerance of uncertainty identified in both groups. Symptomatology was persistent over the lifespan for both groups. Anxiety type was partially associated with repetitive behaviour but not measures of overall ASD phenomenology in CdLS. CONCLUSIONS: DSM-5 and ASD-related anxiety are common in these high-risk syndromes associated with ID. Prospective syndrome specific presentations and associations, which may implicate specific underlying mechanisms, are discussed. Clinicians should be aware of the risk and difficulties involved in assessment of anxiety in individuals with ID, including atypical types, to ensure these individuals do not "miss" diagnoses and support in general clinical practice.

Congenital vaginal obstruction in a female with Cornelia de Lange syndrome: A case report.

Cornelia de Lange syndrome (CdLS) is a rare genetic disease involving multiorgan systems that varies in clinical manifestations. Female genital abnormalities in patients with CdLS are rarely reported, and current guidelines for CdLS contain little information related to female genital abnormalities. We report a case of classic CdLS with an NIPBL gene pathogenic variant in a 4.5-year-old girl who experienced recurrent urinary tract infections (UTIs) with vesical tenesmus. Urogenital physical and imaging examinations revealed external vaginal orifice obstruction and bilateral vesicoureteral reflux (VUR). Vaginal diaphragm-like tissue resection and vaginal orifice plasty were performed on this patient. The symptoms of urination disorders and recurrent UTIs, as well as VUR grading, improved after relieving the vaginal obstruction during the operation. For female CdLS patients, especially those with VUR, it is necessary to check for genital abnormalities and perform timely treatment, which is of great significance in improving urination disorder symptoms, reducing resistance during voiding, decreasing the occurrence of secondary VUR, and controlling recurrent UTIs.

Case Report: Endogenous Candida Endophthalmitis in Cornelia de Lange Syndrome: Atypical Stellate Neuroretinitis.

SIGNIFICANCE: This study aimed to highlight the association of stellate neuroretinitis occurring secondary to endogenous candidemia. PURPOSE: We report an unusual presentation of endogenous Candida endophthalmitis as a stellate neuroretinitis in the setting of Cornelia de Lange syndrome. CASE REPORT: A 34-month-old girl with severe Cornelia de Lange syndrome and a history of parenteral nutrition dependence requiring a chronic central venous catheter presented with bilateral endophthalmitis secondary to candidemia. In one eye, the endophthalmitis had the atypical presentation as a stellate neuroretinitis. CONCLUSIONS: This case represents a unique association of stellate neuroretinitis secondary to Candida infection in a patient with Cornelia de Lange syndrome.

Cornelia de Lange syndrome and congenital diaphragmatic hernia.

PURPOSE: There is a known association between Cornelia de Lange syndrome (CdLS) and congenital diaphragmatic hernia (CDH), with CDH being the cause of death in 5%-20% of CdLS cases. We aimed to identify and describe patients with CDLS and CDH. We hypothesized that CdLS would be associated with high-risk CDH and poor outcomes. METHODS: CDH Study Group patients from 1995 to 2019 were included. Those with CdLS were reviewed retrospectively. Rates of repair and outcomes were compared between patients with and without CdLS. RESULTS: We identified 9,251 CDH patients. Of those, 21 had confirmed CdLS. CdLS patients had a lower birth weight (2.2±0.57 kg) than non-CdLS patients (2.9±0.64 kg) (p<0.001). 5-min Apgar scores were lower in CdLS patients (6, 4-7) than non-CdLS patients (7, 5-8) (p=0.014). Only 33% of CdLS patients underwent diaphragmatic repair compared to 84.2% of non-CdLS patients (p<0.001). Mortality was 76% for CdLS patients compared with 29% for non-CdLS patients (p<0.001). Of the 7 CdLS patients who underwent repair, 5 survived to hospital discharge. CONCLUSIONS: Infants with CdLS and CDH have a poor prognosis. However, CdLS patients who undergo repair can survive to discharge; therefore, the concomitant diagnosis of CdLS and CDH is not necessarily a contraindication to repair. Early recognition of these anomalies can assist with counseling and prognostication. TYPE OF STUDY: Retrospective comparative study LEVEL OF EVIDENCE: III.

Behaviour across the lifespan in Cornelia de Lange syndrome.

PURPOSE OF REVIEW: While previous reviews have extended descriptions of the behavioural phenotype of Cornelia de Lange syndrome (CdLS) significantly, potential changes with age across the lifespan have been neglected. Age-related difference in the behavioural phenotype constitutes preliminary evidence of change with age. Documenting and understanding the developmental trajectories of behaviours is informative as it enables identification of risk periods for behavioural challenges and compromised mental health. RECENT FINDINGS: Recent cross sectional, longitudinal and mixed design studies report differing presentations of the behavioural phenotype across the lifespan. Of particular interest are autistic characteristics and behaviours consistent with compromised mental health, particularly anxiety and negative affect, which are reported to be more common and severe in older individuals. Preliminary evidence for identified causal pathways with consideration of biological, cognitive and environmental factors are discussed. SUMMARY: Older individuals with CdLS appear to be at greater risk of poorer psychological wellbeing than younger peers with significant implications for risk informed preventive and early interventions. Further work is required to document the behavioural phenotype across the lifespan with consideration of multiple factors that may influence the trajectory and extent of negative outcomes.

Severe cortical damage associated with COVID-19 case report.

Symptoms of COVID-19, as reported during the SARS-CoV-2 pandemic in 2019-2020, are primarily respiratory and gastrointestinal, with sparse reports on neurological manifestations. We describe the case of a 17-year old female with Cornelia de Lange syndrome and well controlled epilepsy, who sustained significant cortical injury during a COVID-19 associated multi-inflammatory syndrome.

Repetitive and Self-injurious Behaviors in Children with Cornelia de Lange Syndrome.

Cornelia de Lange syndrome (CdLS) is associated with repetitive and self-injurious behaviors (RBs, SIB). Evaluating children with CdLS, this study: (1) characterizes the spectrum of RBs; (2) characterizes the impact and severity of RBs including SIB; (3) describes how age and adaptive functioning relate to RBs including SIB. Fifty children (5-17 years) with CdLS were assessed with Children's Yale-Brown Obsessive Compulsive Scale Modified for PDD; Aberrant Behavior Checklist (ABC); Vineland Adaptive Behaviors Scales (VABS). All children had ≥ 1 type of RB; 44% had some form of SIB. 64% spent > 1 h/day displaying RBs. Lower VABS adaptive functioning was associated with higher stereotypy and SIB scores (ABC). In children with CdLS, RBs including SIB are common, impactful, and associated with lower adaptive functioning.

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.

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.

Associated syndromes in patients with Pierre Robin Sequence.

OBJECTIVES: Classically, Pierre Robin Sequence (PRS) is a triad of micrognathia, glossoptosis, and airway obstruction, although frequently associated with cleft palate. Current literature reports that Stickler syndrome is the most common syndrome associated with PRS, and 22q11 deletion syndrome (22q11 DS) as the second most common. This study identifies associations between PRS and genetic syndromes. METHODS: A retrospective chart review was performed to identify patients diagnosed with PRS over a 10-year period from 4/1/2007 to 4/1/2017 at a tertiary children's hospital. RESULTS: 4,052 consecutive charts were reviewed and 234 patients had a diagnosis of PRS confirmed with the triad of micrognathia, glossoptosis, and airway obstruction. Of note, all of these patients had cleft palate. Of the 234 patients with PRS, 65 patients had syndromic diagnoses (28%). One patient had 22q11 DS (0.43%), and 31 patients had Stickler syndrome (13.2%). Additionally, 3 patients had central hypoventilation syndrome, 3 patients had Duane syndrome, 2 patients had Cornelia de Lange syndrome, 2 patients had Emanuel syndrome, 2 patients had Gordon syndrome, 2 patients had Mobius syndrome, 2 patients had Nager syndrome. Multiple other syndromes were identified, but occurred in isolated cases. CONCLUSION: This study supports literature that PRS is most commonly associated with Stickler Syndrome but rarely associated with 22q11 DS given that only 1 patient had both PRS and 22q11 DS.

Cornelia de lange manifestations in otolaryngology: A systematic review and meta-analysis.

OBJECTIVES: Cornelia de Lange syndrome (CdLS) is a rare genetic disorder. Our goal was to systematically review the literature regarding otolaryngology manifestations of CdLS. METHODS: We systematically reviewed the PubMed, Embase, CINAHL, Scopus, and Google Scholar databases for original articles of otolaryngology manifestations for patients with CdLS. These articles were analyzed, and pooled prevalence was calculated. RESULTS: We analyzed 1,310 patients included in 35 case series and 34 case reports. Hearing loss was present for many patients (27 studies), with sensorineural hearing loss affecting 40.3% (95% confidence interval [CI]: 17.3-63.4) and conductive affecting 22.7% (95% CI: 5.7-39.7). Recurrent acute otitis media was the most frequent infectious manifestation, with 56.5% (95% CI: 34.1-78.4) in seven studies, followed by recurrent airway infections with 44.1% (95% CI: 11.0-87.1) in five studies. Forty-nine (49.7%) percent of patients (95% CI: 25.9-73.6) in nine studies had dysphagia, and 76.6% (95% CI: 59.8-93.3) in four studies had some degree of dysphonia. Craniofacial anomalies were reported in 30 studies, with micrognathia (53.1%; 95% CI: 34.1-72.1) and high arched palate (70.6%; 95% CI: 56.5-84.8) commonly reported. Additional physical exam abnormalities reported included those involving: lips (76.8%; 95% CI: 65.3-88.4), dentition (65.1%; 95% CI: 27.2-100), mouth (85.5%; 95% CI: 76.2-93.8), and eyelashes (87.1%; 95% CI: 77.2-96.9). Sleep-disordered breathing or obstructive sleep apnea affected 25.8% (95% CI: 11.4-40.2) of patients (7 studies). Airway anomalies were reported in 11 case reports. CONCLUSION: This is the first comprehensive evaluation of otolaryngologic manifestations in the CdLS literature. Most reported hearing loss and craniofacial anomalies. Sleep disorders occurred in a minority of patients, whereas airway disorders were primarily reported in case reports. These conditions should be further examined given their potential life-threatening implications. LEVEL OF EVIDENCE: 3a Laryngoscope, 130:E122-E133, 2020.

Profiles of atypical sensory processing in Angelman, Cornelia de Lange and Fragile X syndromes.

BACKGROUND: There is growing evidence to suggest that children with neurodevelopmental disorders may evidence differences in their sensory processing. The aim of this study was to compare sensory processing patterns in three genetic syndromes associated with sensory difference. METHODS: Sensory processing in Angelman syndrome (n = 91), Cornelia de Lange syndrome (n = 28) and Fragile X syndrome (n = 40) was examined using the informant report measure the Sensory Experiences Questionnaire (SEQ). RESULTS: All three groups were associated with a heightened prevalence of unusual sensory processing in comparison with normative data, evidenced in over 80% of all participants. Cross-syndrome comparisons highlighted syndrome-specific sensory processing profiles, with heightened hypo responsivity in Cornelia de Lange syndrome and sensory seeking in Angelman syndrome. CONCLUSIONS: The results have important implications for the understanding of sensory processing in genetic syndromes and the development of tailored behavioural interventions.

Behavioural and psychological characteristics in Pitt-Hopkins syndrome: a comparison with Angelman and Cornelia de Lange syndromes.

BACKGROUND: Pitt-Hopkins syndrome (PTHS) is a genetic neurodevelopmental disorder associated with intellectual disability. Although the genetic mechanisms underlying the disorder have been identified, description of its behavioural phenotype is in its infancy. In this study, reported behavioural and psychological characteristics of individuals with PTHS were investigated in comparison with the reported behaviour of age-matched individuals with Angelman syndrome (AS) and Cornelia de Lange syndrome (CdLS). METHODS: Questionnaire data were collected from parents/caregivers of individuals with PTHS (n = 24), assessing behaviours associated with autism spectrum disorder (ASD), sociability, mood, repetitive behaviour, sensory processing, challenging behaviours and overactivity and impulsivity. For most measures, data were compared to data for people with AS (n = 24) and CdLS (n = 24) individually matched by adaptive ability, age and sex. RESULTS: Individuals with PTHS evidenced significantly higher levels of difficulties with social communication and reciprocal social interaction than individuals with AS, with 21 of 22 participants with PTHS meeting criteria indicative of ASD on a screening instrument. Individuals with PTHS were reported to be less sociable with familiar and unfamiliar people than individuals with AS, but more sociable with unfamiliar people than individuals with CdLS. Data also suggested areas of atypicality in sensory experiences. Challenging behaviours were reported frequently in PTHS, with self-injury (70.8%) occurring at significantly higher rates than in AS (41.7%) and aggression (54.2%) occurring at significantly higher rates than in CdLS (25%). Individuals with PTHS also evidenced lower reported mood than individuals with AS. CONCLUSIONS: Behaviours which may be characteristic of PTHS include those associated with ASD, including deficits in social communication and reciprocal social interaction. High rates of aggression and self-injurious behaviour compared to other genetic syndrome groups are of potential clinical significance and warrant further investigation. An atypical sensory profile may also be evident in PTHS. The specific aetiology of and relationships between different behavioural and psychological atypicalities in PTHS, and effective clinical management of these, present potential topics for future research.

Perioperative Management of a Patient With Cornelia de Lange Syndrome and Tetralogy of Fallot.

This is a case report of a 21-year-old male patient with Cornelia de Lange syndrome (CdL) and unrepaired tetralogy of Fallot scheduled for dental treatment under general anesthesia. Anticipated dental care consisted of restorative treatment and extractions. Surgical correction of the patient's congenital cardiac abnormalities had not occurred by the time of dental treatment. As such, the developed anesthetic plan included the following goals: prevention of any anoxic episodes or spell and preparation for difficult airway management due to micrognathia secondary to CdL. To help ensure adequacy of oxygenation during induction, the normal anesthetic face mask was specially modified with a hole to permit use of the fiberoptic scope during induction and intubation. With preoperative consultation involving a cardiologist as well as the use of the modified mask, general anesthesia was safely administered without any complications.

Lifespan trajectory of affect in Cornelia de Lange syndrome: towards a neurobiological hypothesis.

BACKGROUND: Depressive symptomology and low affect are comparatively common in individuals with genetic disorders such as Cornelia de Lange syndrome. However, lifespan trajectories and associated person characteristics have not been examined. In this study, the trajectories for affect and associated behavioural characteristics were investigated in individuals with Cornelia de Lange syndrome with individuals with fragile X syndrome (FXS) comparable for chronological age and total number of behavioural indicators of ASD included for the purpose of contrast. METHODS: A 7-year longitudinal study of affect (mood, interest and pleasure) was conducted in individuals with CdLS (n = 44) and FXS (n = 95). The trajectories of low affect were explored, as well as associations between Time 1 behavioural characteristics and affect at Time 1 and Time 3 (7 years later). RESULTS: The CdLS group were lower in mood than the FXS group overall (p < .001). Interest and pleasure scores showed a significant decline over the lifespan for individuals with CdLS (p < .001) but not the FXS group. Lower level of ability at Time 1 was associated with lower mood at Time 1 and Time 3 in the FXS group only. Higher levels of ASD symptomology at Time 1 were associated with low mood and interest and pleasure in both syndrome groups at Time 1 and Time 3. Greater insistence on sameness at Time 1 was associated with lower mood at Time 1 in the FXS group and lower interest and pleasure at Time 1 and Time 3 in the CdLS group. CONCLUSIONS: Low affect in specific genetic syndromes may be associated with differing lifespan trajectories and behavioural profiles. Specifically, individuals with CdLS appear at risk for experiencing declines in levels of interest and pleasure whereas individuals with FXS show no significant change in the level of affect with age.

Congenital Chylothorax in a Neonate with Cornelia de Lange Syndrome: A Rare Complication Managed with a Novel Indigenously Prepared Milk Formulation.

Congenital chylothorax is a relatively uncommon condition seen in newborn period. Treatment comprises of adequate pleural fluid drainage, octreotide infusion, total parenteral nutrition followed by medium chain triglyceride (MCT) based low fat milk preparations. The authors present a case of Cornelia de Lange syndrome with a rare presentation of antenatally diagnosed chlyothorax presenting at birth with respiratory distress. The baby was managed with skimmed milk formulation fortified with coconut oil providing low fat and high proteins.

Development, behaviour and autism in individuals with SMC1A variants.

INTRODUCTION: Development and behaviour in Cornelia de Lange Syndrome (CdLS), including autism characteristics, have been described infrequently stratified to genetic cause and only a few studies have considered behavioural characteristics in relation to developmental level. Here, we describe the behavioural phenotype in individuals with CdLS with SMC1A variants. METHODS: We performed an international, interdisciplinary study on 51 individuals with SMC1A variants. Results of questionnaire studies are compared to those in individuals with Down Syndrome and with Autism Spectrum Disorder. Results on cognition and self-injurious behaviour (SIB) are compared to those in individuals with CdLS caused by NIPBL variants. For Dutch participants with SMC1A variants we performed direct in-person assessments of cognition, autism, and added an interview and questionnaire on adaptive behaviour and sensory processing. RESULTS: Individuals with SMC1A variants show a higher cognitive level and less SIB than individuals with NIPBL variants. Individuals with SMC1A variants without classic CdLS phenotype but with a Rett-like phenotype show more severe intellectual disability and more SIB compared to those with a CdLS phenotype. Autism is less present if outcomes in direct in-person assessments are evaluated taking developmental level into account compared to results based on a questionnaire. CONCLUSIONS: Behaviour in individuals with CdLS should be evaluated taking genetic cause into account. Detailed interdisciplinary approaches are of clinical importance to inform tailored care and may eventually improve quality of life of patients and families.