Background: Autism spectrum disorders (ASD) and intellectual disabilities (ID) are heterogeneous and complex developmental diseases with significant genetic backgrounds and overlaps of genetic susceptibility loci. Copy number variants (CNVs) are known to be frequent causes of these impairments. However, the clinical heterogeneity of both disorders causes the diagnostic efficacy of CNV analysis to be modest. This could be resolved by stratifying patients according to their clinical features. Aim: First, we sought to assess the significance of particular clinical features for the detection of pathogenic CNVs in separate groups of ID and ASD patients and determine whether and how these groups differ from each other in the significance of these variables. Second, we aimed to create a statistical model showing how particular clinical features affect the probability of pathogenic CNV findings. Method: We tested a cohort of 204 patients with ID (N = 90) and ASD (N = 114) for the presence of pathogenic CNVs. We stratified both groups according to their clinical features. Fisher's exact test was used to determine the significance of these variables for pathogenic CNV findings. Logistic regression was used to create a statistical model of pathogenic CNV findings. Results: The frequency of pathogenic CNV was significantly higher in the ID group than in the ASD group: 18 (19.78%) versus 8 (7%) (p < 0.004). Microcephaly showed a significant association with pathogenic findings in ID patients (p < 0.01) according to Fisher's exact test, whereas epilepsy showed a significant association with pathogenic findings in ASD patients (p < 0.01). The probability of pathogenic CNV findings when epilepsy occurred in ASD patients was more than two times higher than if epilepsy co-occurred with ID (29.6%/14.0%). Facial dysmorphism was a significant variable for detecting pathogenic CNVs in both groups (ID p = 0.05, ASD p = 0.01). However, dysmorphism increased the probability of pathogenic CNV detection in the ID group nearly twofold compared to the ASD group (44.4%/23.7%). The presence of macrocephaly in the ASD group showed a 25% probability of pathogenic CNV findings by logistic regression, but this was insignificant according to Fisher's exact test. The probability of detecting pathogenic CNVs decreases up to 1% in the absence of dysmorphism, macrocephaly, and epilepsy in the ASD group. Conclusion: Dysmorphism, microcephaly, and epilepsy increase the probability of pathogenic CNV findings in ID and ASD patients. The significance of each feature as a predictor for pathogenic CNV detection differs depending on whether the patient has only ASD or ID. The probability of pathogenic CNV findings without dysmorphism, macrocephaly, or epilepsy in ASD patients is low. Therefore the efficacy of CNV analysis is limited in these patients.
- Publication type
- Journal Article MeSH
BACKGROUND: Congenital cataract, facial dysmorphism, and neuropathy (CCFDN) syndrome is an extremely rare multiorgan disorder. Characteristics include congenital cataracts, facial deformation, extremity deformities, and demyelinating neuropathy. CCFDN syndrome is associated with increased risk during anesthesia including rhabdomyolysis or epileptic seizures. There is a lack of published information about difficult airways in these patients. Difficult airways during intubation represent one of the most dreaded anesthesia complications: A "can not intubate, can not oxygenate" scenario. Presented herein is the first described successful endotracheal intubation of a CCFDN syndrome patient. CASE SUMMARY: We report the anesthetic management of a 13-year-old girl with CCFDN syndrome scheduled for posterior neuromuscular scoliosis correction surgery. The patient suffered from extensive progressive neuromuscular scoliosis with a Cobb angle of 83°. Her limitations included neuropathy and a scoliotic curve. This condition negatively impacted her quality of life. This case reflects the potential anesthetic complications for posterior scoliosis correction and CCFDN syndrome. The challenge for our anesthetic team was the limited amount of data about anesthetic management of this condition. In total, one case report without any data about endotracheal intubation of patients with this condition was available. Endotracheal intubation in our case was uncomplicated. Another focus of our case was the prevention of possible complications associated with this syndrome, including rhabdomyolysis and seizures. Rhabdomyolysis can be triggered by some types of anesthetic agents like suxamethonium or volatile anesthetics, especially in patients with certain types of myopathies. CONCLUSION: Adequate understanding of the anesthetic management of CCFDN syndrome can reduce perioperative complications and improve patient outcome after surgery.
- Publication type
- Case Reports MeSH
BACKGROUND: Congenital Cataract Facial Dysmorphism and demyelinating Neuropathy (CCFDN, OMIM 604468) is an autosomal recessive multi-system disorder which was first described in Bulgarian Gypsies in 1999. It is caused by the homozygous founder mutation c.863 + 389C > T in the CTDP1 gene. The syndrome has been described exclusively in patients of Gypsy ancestry. The prevalence of this disorder in the Gypsy population in the Czech Republic and Central Europe is not known and is probably underestimated and under-diagnosed. METHODS: We clinically diagnosed and assessed 10 CCFDN children living in the Czech Republic. All patients are children of different ages, all of Gypsy origin born in the Czech Republic. Molecular genetic testing for the founder CTDP1 gene mutation was performed. RESULTS: All patients are homozygous for the c.863 + 389C > T mutation in the CTDP1 gene. All patients presented a bilateral congenital cataract and microphthalmos and had early cataract surgery. Correct diagnosis was not made until the age of two. All patients had variably delayed motor milestones. Gait is characteristically paleocerebellar in all the patients. Mental retardation was variable and usually mild. CONCLUSIONS: Clinical diagnosis of CCFDN should be easy for an informed pediatrician or neurologist by the obligate signalling trias of congenital bilateral cataract, developmental delay and later demyelinating neuropathy. Our data indicate a probably high prevalence of CCFDN in the Czech Gypsy ethnic subpopulation.
- MeSH
- Child MeSH
- Cataract congenital diagnosis etiology MeSH
- Infant MeSH
- Craniofacial Abnormalities diagnosis etiology MeSH
- Humans MeSH
- Adolescent MeSH
- Nervous System Diseases diagnosis etiology MeSH
- Child, Preschool MeSH
- Roma MeSH
- Check Tag
- Child MeSH
- Infant MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Czech Republic MeSH
Genetické zmeny spôsobujú predispozíciu k zvýšenému riziku vzniku nádoru v súvislosti s konštitučnými mutáciami v génoch pre reguláciu rastu alebo opravu DNA. Niektoré detské malignity sú spojené s dysmorfiou vyskytujúcou sa na rôznych častiach tela. Fyzikálnym vyšetrením je možné rozpoznať charakteristické znaky genetických dysmorfických ochorení. Medzi ne patrí: nadmerný či nízky vzrast, makrocefália, mikrocefália a dysmorfické zmeny na tvári, očiach, ústach a perách, srdci, v gastrointestinálnom trakte, na obličkách, genitáliách a skelete. Rozpoznanie dysmorfického syndrómu s malignitou iniciuje pátranie po malignite a genetické poradenstvo pre dieťa a jeho rodinu. Preto sa u každého dieťaťa s malignitou odporúča zvážiť možnosť genetického vyšetrenia. Molekulárna diagnostika zárodočných mutácií môže veľmi účinne odhaliť rodiny s vysokým rizikom malignity a poskytnúť pomoc pri primárnej prevencii. Predložená prehľadová práca predstavuje 18 genetických dysmorfických syndrómov s rizikom malignity, popisuje ich klinické znaky, genetický podklad a odporúčania pre sledovanie pacientov s cieľom skorého zachytenia malignít.
Genetic alterations cause predisposition to malignancy by increased cancer risk related to constitutional mutations in growth-regulating or DNA repair genes. Some pediatric malignancies are associated with dysmorphic features in several body areas. Through physical examination, we recognise characteristic signs of genetic dysmorphic disorders, such as somatic overgrowth, undergrowth, macrocephaly, microcephaly and dysmorphic changes of the face, eyes, mouth and lips, heart, gastrointestinal tract, urinary tract, genitalia and skeleton. Recognition of a cancer-associated dysmorphic syndrome allows intensive cancer screening and genetic counseling. Therefore, it is recommended that every child with cancer should be examined by a clinical geneticist. Molecular diagnostics of germinal mutations may very effectively detect families at high risk of malignancy and help provide primary prevention. This work presents clinical syndromes with genetic backround and cancer screening recommendations for 18 syndromes with increased cancer risk.
- MeSH
- Beckwith-Wiedemann Syndrome diagnosis etiology genetics MeSH
- Bloom Syndrome diagnosis etiology genetics MeSH
- Costello Syndrome diagnosis etiology genetics MeSH
- Child MeSH
- Fanconi Anemia diagnosis etiology genetics MeSH
- Financing, Organized MeSH
- Genetic Diseases, Inborn diagnosis genetics MeSH
- Humans MeSH
- MAP Kinase Signaling System genetics MeSH
- Cell Transformation, Neoplastic genetics MeSH
- Noonan Syndrome diagnosis etiology genetics MeSH
- Proteus Syndrome diagnosis etiology genetics MeSH
- Sotos Syndrome diagnosis etiology genetics MeSH
- Basal Cell Nevus Syndrome diagnosis etiology genetics MeSH
- Hamartoma Syndrome, Multiple diagnosis etiology genetics MeSH
- Nijmegen Breakage Syndrome diagnosis etiology genetics MeSH
- LEOPARD Syndrome diagnosis etiology genetics MeSH
- Ataxia Telangiectasia diagnosis etiology genetics MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Publication type
- Review MeSH
Aesthetic surgery of the female genitalia is on the rise. Many procedures are performed. Body dysmorphic disorder (BDD) is a psychiatric disorder and often goes unrecognized in plastic surgery. This review examines actual knowledge of plastic surgery in gynecology, knowledge of motivational factors of women, and BDD. We carried out a systematic electronic search. We used a combination of relevant keywords to construct the search strategy. Included studies were systematic reviews or primary studies published 1990-2017 and containing information about BDD. Reviewers independently assessed study eligibility, extracted data, and assessed quality, undertaking narrative synthesis. The research revealed a variety of plastic procedures available and why women consider undergoing labia reduction surgery.
- MeSH
- Humans MeSH
- Body Image psychology MeSH
- Decision Making * MeSH
- Patient Satisfaction MeSH
- Body Dysmorphic Disorders psychology surgery MeSH
- Vulva surgery MeSH
- Plastic Surgery Procedures psychology MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
We report two unrelated patients with overlapping chromosome 2q13 deletions (patient 1 in chr2:111415137-113194067 bp and patient 2 in chr2:110980342-113007823 bp, hg 19). Patient 1 presents with developmental delay, microcephaly and mild dysmorphic facial features, and patient 2 with autism spectrum disorder, borderline cognitive abilities, deficits in attention and executive functions and mild dysmorphic facial features. The mother and maternal grandmother of patient 1 were healthy carriers of the deletion. Previously, 2q13 deletions were reported in 27 patients, and the interpretation of its clinical significance varied. Our findings support that the 2q13 deletion is associated with a developmental delay syndrome manifesting with variable expressivity and reduced penetrance which poses a challenge for genetic counselling as well as the clinical recognition of 2q13 deletion patients.
- Publication type
- Journal Article MeSH
- MeSH
- Spectroscopy, Near-Infrared MeSH
- Cholesterol biosynthesis metabolism MeSH
- Diagnosis, Differential MeSH
- Child MeSH
- Adrenal Hyperplasia, Congenital MeSH
- Humans MeSH
- Infant, Newborn, Diseases MeSH
- Infant, Newborn MeSH
- Smith-Lemli-Opitz Syndrome diagnosis etiology MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Infant, Newborn MeSH
- Publication type
- Case Reports MeSH
- Review MeSH
Pediatric obstructive sleep apnea (POSA) is a complex disease with multifactorial etiopathogenesis. The presence of craniofacial dysmorphisms influencing the patency of the upper airway is considered a risk factor for POSA development. The craniofacial features associated with sleep-related breathing disorders (SRBD) - craniosynostosis, retrognathia and micrognathia, midface and maxillary hypoplasia - have high heritability and, in a less severe form, could be also found in non-syndromic children suffering from POSA. As genetic factors play a role in both POSA and craniofacial dysmorphisms, we hypothesize that some genes associated with specific craniofacial features that are involved in the development of the orofacial area may be also considered candidate genes for POSA. The genetic background of POSA in children is less explored than in adults; so far, only one genome-wide association study for POSA has been conducted; however, children with craniofacial disorders were excluded from that study. In this narrative review, we discuss syndromes that are commonly associated with severe craniofacial dysmorphisms and a high prevalence of sleep-related breathing disorders (SRBD), including POSA. We also summarized information about their genetic background and based on this, proposed 30 candidate genes for POSA affecting craniofacial development that may play a role in children with syndromes, and identified seven of these genes that were previously associated with craniofacial features risky for POSA development in non-syndromic children. The evidence-based approach supports the proposition that variants of these candidate genes could lead to POSA phenotype even in these children, and, thus, should be considered in future research in the general pediatric population.
- Publication type
- Journal Article MeSH
- Review MeSH
428 s. : il.
