scholarly journals Pitt-Hopkins Syndrome: A Review of Current Literature, Clinical Approach, and 23-Patient Case Series

2018 ◽  
Vol 33 (3) ◽  
pp. 233-244 ◽  
Author(s):  
Kimberly Goodspeed ◽  
Cassandra Newsom ◽  
Mary Ann Morris ◽  
Craig Powell ◽  
Patricia Evans ◽  
...  
Keyword(s):  
Genetic Disorder ◽  
Somatic Mosaicism ◽  
Case Series ◽  
Autism Spectrum ◽  
Facial Features ◽  
Clinical Approach ◽  
Psychomotor Delay ◽  
Verbal Skills ◽  
Molecular Variant ◽  
Chromosomal Duplication

Pitt-Hopkins syndrome (PTHS) is a rare, genetic disorder caused by a molecular variant of TCF4 which is involved in embryologic neuronal differentiation. PTHS is characterized by syndromic facies, psychomotor delay, and intellectual disability. Other associated features include early-onset myopia, seizures, constipation, and hyperventilation-apneic spells. Many also meet criteria for autism spectrum disorder. Here the authors present a series of 23 PTHS patients with molecularly confirmed TCF4 variants and describe 3 unique individuals. The first carries a small deletion but does not exhibit the typical facial features nor the typical pattern of developmental delay. The second exhibits typical facial features, but has attained more advanced motor and verbal skills than other reported cases to date. The third displays typical features of PTHS, however inherited a large chromosomal duplication involving TCF4 from his unaffected father with somatic mosaicism. To the authors’ knowledge, this is the first chromosomal duplication case reported to date.

scholarly journals Is Visual Pedagogy Effective in Improving Cooperation towards Oral Hygiene and Dental Care in Children with Autism Spectrum Disorder? A Systematic Review and Meta-Analysis

2021 ◽  
Vol 18 (2) ◽  
pp. 789
Author(s):  
Araxi Balian ◽  
Silvia Cirio ◽  
Claudia Salerno ◽  
Thomas Gerhard Wolf ◽  
Guglielmo Campus ◽  
...  
Keyword(s):  
Dental Care ◽  
Oral Hygiene ◽  
Meta Analysis ◽  
Scientific Evidence ◽  
Case Series ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Conclusive Evidence ◽  
Cross Sectional ◽  
Visual Pedagogy

Visual pedagogy has emerged as a new approach in improving dental care in children with autism spectrum disorders (ASDs). This paper aimed to evaluate and assess the scientific evidence on the use of visual pedagogy in improving oral hygiene skills and cooperation during dental care in children with ASDs. The review protocol was registered on the PROSPERO Register (CRD42020183030). Prospective clinical studies, randomized trials, interruptive case series, before and after comparison studies, and cross-sectional studies following the PRISMA guideline were searched in PubMed, Embase, Scopus, and Google Scholar using ad hoc prepared search strings. The search identified 379 papers, of which 342 were excluded after title and abstract evaluation, and 37 full-text papers were analyzed. An additional four papers were added after consulting reference lists. Eighteen papers were disregarded; 23 were finally included, and their potential bias was assessed using ROB-2 and ROBINS-I tools. The wide heterogenicity of the studies included does not allow for conclusive evidence on the effectiveness of visual pedagogy in oral hygiene skills and dental care. Nevertheless, a significant and unilateral tendency of the overall outcomes was found, suggesting that visual pedagogy supports ASD children in improving both oral hygiene skills and cooperation during dental care.

scholarly journals Cerebrospinal fluid liquid biopsy for detecting somatic mosaicism in brain

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Zimeng Ye ◽  
Zac Chatterton ◽  
Jahnvi Pflueger ◽  
John A Damiano ◽  
Lara McQuillan ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Liquid Biopsy ◽  
Somatic Mutations ◽  
Somatic Mosaicism ◽  
Autism Spectrum ◽  
Brain Diseases ◽  
Cell Free Dna ◽  
Free Dna ◽  
Subcortical Band Heterotopia ◽  
Fluid Cell

Abstract Brain somatic mutations are an increasingly recognized cause of epilepsy, brain malformations and autism spectrum disorders and may be a hidden cause of other neurodevelopmental and neurodegenerative disorders. At present, brain mosaicism can be detected only in the rare situations of autopsy or brain biopsy. Liquid biopsy using cell-free DNA derived from cerebrospinal fluid has detected somatic mutations in malignant brain tumours. Here, we asked if cerebrospinal fluid liquid biopsy can be used to detect somatic mosaicism in non-malignant brain diseases. First, we reliably quantified cerebrospinal fluid cell-free DNA in 28 patients with focal epilepsy and 28 controls using droplet digital PCR. Then, in three patients we identified somatic mutations in cerebrospinal fluid: in one patient with subcortical band heterotopia the LIS1 p. Lys64* variant at 9.4% frequency; in a second patient with focal cortical dysplasia the TSC1 p. Phe581His*6 variant at 7.8% frequency; and in a third patient with ganglioglioma the BRAF p. Val600Glu variant at 3.2% frequency. To determine if cerebrospinal fluid cell-free DNA was brain-derived, whole-genome bisulphite sequencing was performed and brain-specific DNA methylation patterns were found to be significantly enriched (P = 0.03). Our proof of principle study shows that cerebrospinal fluid liquid biopsy is valuable in investigating mosaic neurological disorders where brain tissue is unavailable.

scholarly journals 0897 Sleep Disordered Breathing In Pediatric Patients With Turner Syndrome

SLEEP ◽  
2020 ◽  
Vol 43 (Supplement_1) ◽  
pp. A341-A342
Author(s):  
Y A Yu ◽  
B V Vaughn
Keyword(s):  
Sleep Apnea ◽  
Turner Syndrome ◽  
Sleep Disordered Breathing ◽  
Pediatric Patients ◽  
Genetic Disorder ◽  
Case Series ◽  
Growth Failure ◽  
Retrospective Chart Review ◽  
Upper Airway Resistance Syndrome ◽  
Disordered Breathing

Abstract Introduction Turner syndrome (TS) is a common genetic disorder that affects phenotypic females with partial or complete absence of one X chromosome. It typically presents with characteristic facial appearance, neck webbing, lymphedema, linear growth failure, and ovarian insufficiency. TS is also associated with other disorders, though sleep related disorders are not commonly reported. We present a case series of pediatric patients diagnosed with TS and assess their risk for sleep disordered breathing. Methods This study utilized retrospective chart review of the electronic medical record at the University of North Carolina at Chapel Hill from April 2014 to January 2019. Only pediatric patients under the age of 18 years who had previously undergone polysomnography and carrying the diagnosis of Turner syndrome were included in this study. Polysomnography results were reviewed. Results Retrospective chart analysis yielded ten (10) patients who qualified for inclusion. The mean age was 8.3 years (age range 1-15 years). Nine (9) patients were found to have sleep disordered breathing ranging from upper airway resistance syndrome to moderate sleep apnea (AHI range 1.2 to 6.2). Six (6) patients were found to have elevated periodic limb movement indices (PLM index range 5.1 to 30). Parasomnias and hypoventilation were not seen. Conclusion Our case series illustrates that sleep disordered breathing may be more common in TS than previously realized. Eklund et al. found that females with TS had more retrognathic mandibles and maxillas, shorter mandibles, and larger cranial base angles. These findings may indicate elevated risk of sleep apnea. Further studies are needed to define the overall risk of sleep disordered breathing in TS. Support None.

scholarly journals Association of psychiatric comorbidities with the risk of transport accidents in ADHD and MPH

2021 ◽  
Vol 30 ◽  
Author(s):  
Yi-Chun Liu ◽  
Vincent Chin-Hung Chen ◽  
Yao-Hsu Yang ◽  
Yi-Lung Chen ◽  
Michael Gossop
Keyword(s):  
Dose Response ◽  
Case Series ◽  
Autism Spectrum ◽  
Research Database ◽  
Accident Risk ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Series Analysis ◽  
The Relationship ◽  
Transport Accidents

Abstract Aims Although the relationship between attention-deficit/hyperactivity disorder (ADHD) and transport accidents has been shown, there is limited information on the relationship between medication and dose–response effects and transport accident risk. This study aims to determine whether young people with ADHD, including adolescents, are more prone to transport accidents than those without, and the extent to which methylphenidate (MPH) prescription in these patients reduces the risk. Methods We identified 114 486 patients diagnosed with ADHD from Taiwan's National Health Insurance Research Database from 1997 to 2013. Using a Cox regression model, we compared the risk of transport accidents between ADHD and non-ADHD groups and estimated the effect of MPH on accidents. Furthermore, we applied a self-control case-series analysis to compare the risk of accidents during the medication periods with the same patients' non-medication periods. Results Male ADHD patients had a higher risk of transport accidents than non-ADHD individuals (adjusted hazard ratio [aHR] = 1.24, [95% confidence interval (CI) 1.10–1.39]), especially for those comorbid with epilepsy, oppositional defiant disorder/conduct disorder (ODD/CD), and intellectual disabilities (ID). Female ADHD patients showed no relationship, except for comorbid with autism spectrum disorder (ASD) or ID. We found a reduced risk of transport accidents in patients with ADHD with MPH medication than those without MPH, with a plausible dose–response relationship (aHR of 0.23 to 0.07). A similar pattern was found in self-controlled case-series analysis. Conclusions Male patients with ADHD, especially those comorbid with epilepsy, ODD/CD, or ID, were at high risk of transport accidents. Female patients, when comorbid with ASD or ID, also exhibited a higher risk of accidents. MPH treatment lowered the accident risk with a dose–response relationship.

scholarly journals Pitt–Hopkins syndrome with electrical stat us epileptic us in slo w-wave sleep: a case report

2019 ◽  
Vol 14 (2) ◽  
pp. 42-48
Author(s):  
N. G. Lyukshina
Keyword(s):  
Case Report ◽  
Intellectual Disability ◽  
Status Epilepticus ◽  
Neuronal Differentiation ◽  
Clinical Case ◽  
Genetic Disorder ◽  
Facial Dysmorphism ◽  
Autistic Behavior ◽  
Rare Genetic Disorder ◽  
Molecular Variant

Pitt–Hoppkins syndrome is rare genetic disorder caused by a molecular variant of TCF4 which is involved in embryologic neuronal differentiation. The syndrome is characterized by specific facial dysmorphism, phychomotor delay, autistic behavior and intellectual disability. Other associated features include ealy-onset myopia, seizures, constipation and hyperventilation-apneic spells. We introduced a clinical case of the patient with molecularly confirmed TCF4 variant and previously undescribed combination with syndrome of the electrical status epilepticus during sleep.

scholarly journals Case Report: Recurrent Variant c.298 TA in CCN6 Gene Found in Progressive Pseudorheumatoid Dysplasia Patients From Patni Community of Gujarat: A Report of Three Cases

2021 ◽  
Vol 12 ◽  
Author(s):  
Harsh Sheth ◽  
Jhanvi Shah ◽  
Aadhira Nair ◽  
Premal Naik ◽  
Jayesh Sheth
Keyword(s):  
Genetic Disorder ◽  
Case Series ◽  
Missense Variant ◽  
Community Analysis ◽  
Gait Disturbance ◽  
Mutant Genotype ◽  
Progressive Pseudorheumatoid Dysplasia ◽  
First Case ◽  
Abnormal Posture ◽  
Biallelic Mutations

Biallelic mutations in the CCN6 gene are known to cause a rare genetic disorder—progressive pseudorheumatoid dysplasia (PPD). PPD is characterized by distinct joint deformities of interphalangeal joints, stiffness, gait disturbance, abnormal posture, and absence of inflammation, resulting in significant morbidity. The largest case series of PPD from India suggests c.233G>A and c.1010G>A to be the most common mutations in the CCN6 gene, although the distribution of these variants among endogamous communities in India has not been carried out. We here report three cases of PPD from three independent families belonging to the Patni community of Gujarat, a community known to practice endogamy. All three cases had short stature, gait disturbance, scoliosis, and interphalangeal joint deformities. Analysis by whole-exome sequencing in the first case showed the presence of a previously known, homozygous, missense variant c.298T>A (p.Cys100Ser) in exon 3 of the CCN6 gene in all cases. Due to all three families belonging to the same community, analysis by Sanger sequencing in the remaining two cases for the variant mentioned earlier showed both cases to be of homozygous mutant genotype. Unaffected family members, i.e., parents and siblings, were either heterozygous carriers or wildtype for the said variant. The present case series is the first report of a recurrent variant occurring across multiple PPD-affected individuals from unrelated families belonging to the same community from India.

scholarly journals Cantu syndrome and hypopituitarism: implications for endocrine monitoring

2019 ◽  
Vol 2019 ◽  
Author(s):  
Nicholas J Theis ◽  
Toby Calvert ◽  
Peter McIntyre ◽  
Stephen P Robertson ◽  
Benjamin J Wheeler
Keyword(s):  
Anterior Pituitary ◽  
Autosomal Dominant ◽  
Genetic Disorder ◽  
Facial Features ◽  
Pituitary Hormone ◽  
List Type ◽  
Pituitary Dysfunction ◽  
Pathogenic Variants ◽  
Clinical Surveillance ◽  
Learning Points

Summary Cantu syndrome, or hypertrichotic osteochondrodysplasia, is a rare, autosomal dominant genetically heterogeneous disorder. It is characterized by hypertrichosis, cardiac and skeletal anomalies and distinctive coarse facial features. We report a case where slowed growth velocity at 13 years led to identification of multiple pituitary hormone deficiencies. This adds to other reports of pituitary abnormalities in this condition and supports inclusion of endocrine monitoring in the clinical surveillance of patients with Cantu syndrome. Learning points: Cantu syndrome is a rare genetic disorder caused by pathogenic variants in the ABCC9 and KCNJ8 genes, which result in gain of function of the SUR2 or Kir6.1 subunits of widely expressed KATP channels. The main manifestations of the syndrome are varied, but most commonly include hypertrichosis, macrosomia, macrocephaly, coarse ‘acromegaloid’ facies, and a range of cardiac defects. Anterior pituitary dysfunction may be implicated in this disorder, and we propose that routine screening should be included in the clinical and biochemical surveillance of patients with Cantu syndrome.

scholarly journals Hyperferritinemia in patients with nonalcoholic fatty liver disease

2017 ◽  
Vol 63 (3) ◽  
pp. 284-289 ◽  
Author(s):  
Raffaelle K Barros ◽  
Helma Pinchemel Cotrim ◽  
Carla H Daltro ◽  
Yanaihara A Oliveira
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Liver Diseases ◽  
Elevated Serum ◽  
Case Series ◽  
Clinical Approach ◽  
Retrospective Case ◽  
Nonalcoholic Fatty Liver

Summary Objective: In liver diseases, hyperferritinemia (HYF) is related to injured cells in acquired and genetic conditions with or without iron overload. It is frequent in patients with nonalcoholic fatty liver disease (NAFLD), in which it is necessary to define the mean of HYF to establish the better approach for them. The present study evaluated the significance of elevated ferritin in patients with NAFLD and steatohepatitis (NASH). Method: The review was performed using search instruments of indexed scientific material, including MEDLINE (by PubMed), Web of Science, IBECS and LILACS, to identify articles published in Portuguese, English and Spanish, from 2005 to May, 2016. Studies eligible included place and year of publication, diagnose criteria to NAFLD, specifications of serum ferritin measurements and/or liver histopathologic study. Exclusion criteria included studies with patients with alcohol consumption ≥ 20 g/day and other liver diseases. Results: A total of 11 from 30 articles were selected. It included 3,564 patients and they were cross-sectional, retrospective, case series and case-control. The result's analyses showed in 10 of these studies a relationship between ferritin elevated serum levels and NAFLD/NASH with and without fibrosis and insulin resistance. Conclusion: Hyperferritinemia in patients with NAFLD/NASH is associated more frequently with hepatocellular injury than hemochromatosis. These data suggest the relevance to evaluate carefully HYF in patients with NAFLD/NASH to establish appropriate clinical approach.

Three Patients with CPT1A Deficiency: Literature Review and Case Series

2020 ◽  
Author(s):  
Naser Ali Mirhosseini ◽  
Mahdieh Saatchi ◽  
Sana Taghiyar
Keyword(s):  
Genetic Disorder ◽  
Case Series ◽  
Autosomal Recessive Inheritance ◽  
Abnormal Liver Function Test ◽  
Medical Procedures ◽  
Main Method ◽  
Appropriate Treatment ◽  
Liver And Kidney ◽  
Renal Tubular

Background: Carnitine palmitoyltransferase 1A deficiency is a rare genetic disorder with autosomal recessive inheritance pattern of fatty acid metabolism secondary to CPT1A mutation. Several dozen infants and children have been described with a deficiency of the liver and kidney CPT1 isoenzyme (CPT1-A). Clinical manifestation includes fasting-induced hypoketotic hypoglycemia, occasionally with extremely abnormal liver function test (LFT) and rarely with renal tubular acidosis. Acyl carnitine analysis has been the main method for the diagnosis of CPT1A deficiency.  Prompt treatment of hypoglycemia includes intravenous fluid containing 10% dextrose. To prevent hypoglycemia, infants should eat frequently during the day and have cornstarch continuously at night. Fasting should not last more than 12 hours during illness, surgery, or medical procedures. Case Presentation: We reported three patients with CPT1A deficiency presented with hypoglycemia and Reye like syndrome in early childhood that with early diagnosis and treatment they are well in follow-up. Conclusion: Prognosis of this genetic disorder will be good with appropriate treatment.

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