Dysmorphic features: common syndromes and sequences

This issue of eMedRef provides information to clinicians on the pathophysiology, diagnosis, and therapeutics of common syndromes and sequences fund with dysmorphic features

Andersen-Tawil Syndrome

Andersen-Tawil syndrome (ATS) is a rare condition consisting of ventricular arrhythmias, periodic paralysis, and dysmorphic features. In 2001, mutations in KCNJ2, which encodes the α subunit of the potassium channel Kir2.1, were identified in patients with ATS. To date, KCNJ2 is the only gene implicated in ATS, accounting for approximately 60% of cases. ATS is a unique channelopathy, and represents the first link between cardiac and skeletal muscle excitability. The arrhythmias observed in ATS are distinctive; patients may be asymptomatic, or minimally symptomatic despite a high arrhythmia burden with frequent ventricular ectopy and bidirectional ventricular tachycardia. However, patients remain at risk for life-threatening arrhythmias, including torsades de pointes and ventricular fibrillation, albeit less commonly than observed in other genetic arrhythmia syndromes. The characteristic heterogeneity at both the genotypic and phenotypic levels contribute to the continued difficulties with appropriate diagnosis, risk stratification, and effective therapy. The initial recognition of a syndromic association of clinically diverse symptoms, and the subsequent identification of the underlying molecular genetic basis of ATS has enhanced both clinical care, and our understanding of the critical function of Kir2.1 on skeletal muscle excitability and cardiac action potentia

Cognitive behavioral therapy for body image and self-care (CBT-BISC) in sexual minority men living with HIV: a randomized controlled trial

OBJECTIVE: Body image disturbance is a distressing and interfering problem among many sexual minority men living with HIV, and is associated with elevated depressive symptoms and poor HIV self-care (e.g., antiretroviral therapy [ART] nonadherence). The current study tested the preliminary efficacy of a newly created intervention: cognitive–behavioral therapy for body image and self-care (CBT-BISC) for this population. METHOD: The current study entailed a 2-arm randomized controlled trial (N = 44) comparing CBT-BISC to an enhanced treatment as usual (ETAU) condition. Analyses were conducted at 3 and 6 months after baseline. The primary outcome was body image disturbance (BDD-YBOCS), and secondary outcomes were ART adherence (electronically monitored via Wisepill), depressive symptoms (MADRS), and global functioning (GAF). RESULTS: At 3 months, the CBT-BISC condition showed substantial improvement in BDD-YBOCS (b = −13.6, SE = 2.7, 95% CI [−19.0, −8.3], p < .001; dppc2 = 2.39); MADRS (b = −4.9, SE = 2.8, 95% CI [−10.6, .70], p = .086; dppc2 = .87); ART adherence (b = 8.8, SE = 3.3, 95% CI [2.0, 15.6], p = .01; dppc2 = .94); and GAF (b = 12.3, SE = 3.2, 95% CI [6.1, 18.6], p < .001; dppc2 = 2.91) compared with the ETAU condition. Results were generally maintained, or improved, at 6 months; although, adherence findings were mixed depending on the calculation method. CONCLUSIONS: CBT-BISC shows preliminary efficacy in the integrated treatment of body image disturbance and HIV self-care behaviors among sexual minority men living with HIV. (APA PsycInfo Database Record (c) 2019 APA, all rights reserved)Funding from this project came from K23MH096647. Author time for Steven A. Safren was supported by K24DA040489 (formally K24MH094214). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health or the National Institutes of Health. (K23MH096647; K24DA040489; K24MH094214)Accepted manuscrip

Classical cornelia de lange syndrome

These two case reports illustrate the importance of doing a thorough dysmorphology examination for all so called “Multiple congenital anomalies” children and attempting to fit them into a recognizedsyndrome. Well over 2000 dysmorphic syndromes are now recognized and diagnosis of these children can be extremely difficult

Human Inborn Errors of Immunity: 2019 Update of the IUIS Phenotypical Classification.

Since 2013, the International Union of Immunological Societies (IUIS) expert committee (EC) on Inborn Errors of Immunity (IEI) has published an updated phenotypic classification of IEI, which accompanies and complements their genotypic classification into ten tables. This phenotypic classification is user-friendly and serves as a resource for clinicians at the bedside. There are now 430 single-gene IEI underlying phenotypes as diverse as infection, malignancy, allergy, autoimmunity, and autoinflammation. We herein report the 2019 phenotypic classification, including the 65 new conditions. The diagnostic algorithms are based on clinical and laboratory phenotypes for each of the ten broad categories of IEI

Role of fetal MRI in the evaluation of isolated and non-isolated corpus callosum dysgenesis: results of a cross-sectional study

PURPOSE: The aims of this study were to characterize isolated and non-isolated forms of corpus callosum dysgenesis (CCD) at fetal magnetic resonance imaging (MRI) and to identify early predictors of associated anomalies. METHODS: We retrospectively analyzed 104 fetuses with CCD undergoing MRI between 2006 and 2016. Corpus callosum, cavum septi pellucidi, biometry, presence of ventriculomegaly, gyration anomalies, cranio-encephalic abnormalities and body malformations were evaluated. Results of genetic tests were also recorded. RESULTS: At MRI, isolated CCD was 26.9%, the rest being associated to other abnormalities. In the isolated group, median gestational age at MRI was lower in complete agenesis than in hypoplasia (22 vs 28 weeks). In the group with additional findings, cortical dysplasia was the most frequently associated feature (P = 0.008), with a more frequent occurrence in complete agenesis (70%) versus other forms; mesial frontal lobes were more often involved than other cortical regions (P = 0.006), with polymicrogyria as the most frequent cortical malformation (40%). Multivariate analysis confirmed the association between complete agenesis and cortical dysplasia (odds ratio = 7.29, 95% confidence interval 1.51-35.21). CONCLUSIONS: CCD is often complicated by other intra-cranial and extra-cranial findings (cortical dysplasias as the most prevalent) that significantly affect the postnatal prognosis. The present study showed CCD with associated anomalies as more frequent than isolated (73.1%). In isolated forms, severe ventriculomegaly was a reliable herald of future appearance of associated features

Predictors of Comorbid Eating Disorders and Association with Other Obsessive-Compulsive Spectrum Disorders in Trichotillomania

Trichotillomania (TTM) and eating disorders (ED) share many phenomenological similarities, including ritualized compulsive behaviors. Given this, and that comorbid EDs may represent additional functional burden to hair pullers, we sought to identify factors that predict diagnosis of an ED in a TTM population. Subjects included 555 adult females (age range 18–65) with DSM-IV-TR TTM or chronic hair pullers recruited from multiple sites. 7.2% (N = 40) of our TTM subjects met criteria for an ED in their lifetime. In univariable regression analysis, obsessive-compulsive disorder (OCD), Yale-Brown Obsessive Compulsive Scale (Y-BOCS) worst-ever compulsion and total scores, certain obsessive-compulsive spectrum disorders, anxiety disorder, attention-deficit/hyperactivity disorder (ADHD), and substance disorder all met the pre-specified criteria for inclusion in the multivariable analysis. In the final multivariable model, diagnosis of OCD (OR: 5.68, 95% CI: 2.2–15.0) and diagnosis of an additional body-focused repetitive behavior disorder (BFRB) (OR: 2.69, 95% CI: 1.1–6.8) were both associated with increased risk of ED in TTM. Overall, our results provide further support of the relatedness between ED and TTM. This finding highlights the importance of assessing for comorbid OCD and additional BFRBs in those with TTM. Future research is needed to identify additional predictors of comorbid disorders and to better understand the complex relationships between BFRBs, OCD and EDs

Cytogenetic diagnosis of Roberts SC phocomelia syndrome: First report from Kashmir

There are several syndromes in which specific mitotic chromosomal abnormalities can be seen, like premature centromere separation, premature (sister) chromatid separation, and somatic aneuploidies. Identifications of such specific cytogenetic findings can be the key factor that leads towards the diagnosis of syndromes like Roberts SC phocomelia. The case presented here as Roberts SC phocomelia syndrome was identified as a child with multiple congenital anomalies and dysmorphic features. Conventional cytogenetic analysis of the case revealed premature sister chromatid separation. The premature centromeric separation was also confirmed by C banding analysis of the child. It is the first and the only case of Roberts SC phocomelia diagnosed from this part of the world. The present case report emphasizes the importance of conventional cytogenetics in the diagnosis of such syndromes

CNV and nervous system diseases - what's new?

Several new genomic disorders caused by copy number variation (CNV) of genes whose dosage is critical for the physiological function of the nervous system have been recently identified. Dup(7)(q11.23) patients carry duplications of the genomic region deleted in Williams-Beuren syndrome, they are characterized by prominent speech delay. The phenotypes of Potocki-Lupski syndrome and MECP2 duplication syndrome were neuropsychologically examined in detail, which revealed autism as an endophenotype and a prominent behavioral feature of these disorders. Tandem duplication of LMNB1 was reported to cause adult-onset autosomal dominant leukodystrophy. PAFAH1B1/LIS1 and YWHAE, which were deleted in isolated lissencephaly (PAFAH1B1/LIS1 alone) and Miller-Dieker syndrome (both genes), were found to be duplicated in patients with developmental delay. Finally, two novel microdeletion syndromes affecting 17q21.31 and 15q13.3, as well as their reciprocal duplications, were also identified. In this review, we provide an overview of the phenotypic manifestation of these syndromes and the rearrangements causing them. Copyright (C) 2009 S. Karger AG, Base