Retinal dystrophy in two boys with Costello syndrome due to the HRAS p.Gly13Cys mutation
Features of Costello Syndrome, a systemic disorder caused by germline mutations in the proto‐oncogene HRAS from the RAS/MAPK pathway, include failure‐to‐thrive, short stature, coarse facial features, cardiac defects including hypertrophic cardiomyopathy, intellectual disability, and predisposition to neoplasia. Two unrelated boys with Costello syndrome and an HRAS mutation (p.Gly13Cys) are presented with their ophthalmologic findings. Both had early symptoms of nystagmus, photophobia, and vision abnormalities. Fundus examination findings of retinal dystrophy were present at age 3 years. Both boys have abnormal electr...
Source: American Journal of Medical Genetics Part A - March 24, 2017 Category: Genetics & Stem Cells Authors: Mary Ella Pierpont, Mary Richards, W. Keith Engel, Nancy J. Mendelsohn, C. Gail Summers Tags: CLINICAL REPORT Source Type: research
A novel patient with an attenuated Costello syndrome phenotype due to an HRAS mutation affecting codon 146 —Literature review and update
We report on a patient with de novo missense mutation causing an amino acid change at codon 146 of HRAS, c.436G > C:p.Ala146Pro, who presented with subtle dysmorphic features, failure to thrive, global developmental delay, and hypertrophic obstructive cardiomyopathy. Mutations affecting codon 146 are observed in <1% of patients with Costello syndrome. From literature search, there were only two other patients reported with mutations involving the same location. We summarized and updated their findings, and discussed evidence to show that these patients with less obvious signs of Costello syndrome may not necessar...
Source: American Journal of Medical Genetics Part A - March 22, 2017 Category: Genetics & Stem Cells Authors: Annie Ting Gee Chiu, Gordon Ka ‐Chun Leung, Yoyo Wing‐Yiu Chu, Karen W. Gripp, Brian Hon‐Yin Chung Tags: CLINICAL REPORT Source Type: research
Novel pathogenic variant in the HRAS gene with lethal outcome and a broad phenotypic spectrum among Polish patients with Costello syndrome
In this study, a molecular and clinical analysis was carried out in eight Polish patients with the Costello phenotype. A molecular test showed two known heterozygous mutations in the first coding exon of the gene in seven patients: p.G12S (n=4) and p.G12A (n=3), and a novel pathogenic variant p.G60V in one child with an unusually severe, lethal course of the syndrome. In addition, a fatal course of CS was present in one patient with the p.G12A mutation and in another with p.G12S, there was a co-occurrence of Turner syndrome because of the distal Xp deletion. A severe clinical manifestation with a lethal outcome in an indiv...
Source: Clinical Dysmorphology - March 6, 2017 Category: Genetics & Stem Cells Tags: Original Articles Source Type: research
Autism spectrum disorder and other neurobehavioural comorbidities in rare disorders of the Ras/MAPK pathway
AimTo investigate the cognitive and behavioural phenotype in rare disorders of the Ras/MAPK pathway, namely Noonan, cardiofaciocutaneous (CFC), and Costello syndromes, particularly prevalence of autism spectrum disorder (ASD) and attention‐deficit–hyperactivity disorder (ADHD).
MethodFifty children were recruited over 10 months through the regional genetics service and advertisements. A range of parent, child, and observational measures were administered including Autism Diagnostic Interview‐Revised and Autism Diagnostic Observation Scale.
ResultsUsing the Collaborative Programme for Excellence in Autism criteria, 12...
Source: Developmental Medicine and Child Neurology - February 4, 2017 Category: Child Development Authors: Shruti Garg, Ami Brooks, Amy Burns, Emma Burkitt ‐Wright, Bronwyn Kerr, Susan Huson, Richard Emsley, Jonathan Green Tags: Original Article Source Type: research
Noonan syndrome - a new survey.
Authors: Tafazoli A, Eshraghi P, Koleti ZK, Abbaszadegan M
Abstract
Noonan syndrome (NS) is an autosomal dominant disorder with vast heterogeneity in clinical and genetic features. Various symptoms have been reported for this abnormality such as short stature, unusual facial characteristics, congenital heart abnormalities, developmental complications, and an elevated tumor incidence rate. Noonan syndrome shares clinical features with other rare conditions, including LEOPARD syndrome, cardio-facio-cutaneous syndrome, Noonan-like syndrome with loose anagen hair, and Costello syndrome. Germline mutations in t...
Source: Archives of Medical Science - February 2, 2017 Category: Journals (General) Tags: Arch Med Sci Source Type: research
Prenatal genetic diagnosis of Costello Syndrome in a male fetus with recurrent HRAS mutation p.Gly12Ser
(Source: Prenatal Diagnosis)
Source: Prenatal Diagnosis - December 31, 2016 Category: Perinatology & Neonatology Authors: Jennifer Hague, Gerald Hackett, Carlo Acerini, Soo ‐Mi Park Tags: Research Letter Source Type: research
Palmoplantar Keratoderma in Costello Syndrome Responsive to Acitretin
We report a case of CS with severe PPK that improved dramatically with systemic administration of acitretin 0.3 mg/kg/day. (Source: Pediatric Dermatology)
Source: Pediatric Dermatology - October 31, 2016 Category: Dermatology Authors: Nareh V. Marukian, Jonathan L. Levinsohn, Brittany G. Craiglow, Leonard M. Milstone, Keith A. Choate Tags: Case Report Source Type: research
Before and after-Nutritional transformation of dysmorphism in a case of Costello syndrome.
We present a 7 months old child with severe failure to thrive whose "subtle" facial dysmorphism at the time eluded clinical recognition of the syndrome. It was only with optimization of his nutritional status that dysmorphic features became more apparent, which affirmed the molecular diagnosis of Costello syndrome from exome sequencing. The case illustrated how drastic failure to thrive can be in Costello syndrome, and how nutritional status can transform dysmorphic features in a child. It also highlights the importance of serial dysmorphic evaluation in difficult cases.
PMID: 27705751 [PubMed - as supplied by publ...
Source: European Journal of Medical Genetics - October 1, 2016 Category: Genetics & Stem Cells Authors: Chiu AT, Zhu L, Mok GT, Leung GK, Chow CB, Chung BH Tags: Eur J Med Genet Source Type: research
EP05.10: Doppler assessment of hypertrophic cardiomyopathy in a case of Costello syndrome
(Source: Ultrasound in Obstetrics and Gynecology)
Source: Ultrasound in Obstetrics and Gynecology - September 7, 2016 Category: Radiology Authors: Y. Kurihara, D. Tachibana, R. Uemura, N.W. Yokoi, R.K. Pooh, F. Kenji, Y. Kawauchi, S. Mika, T. Suzuki, Y. Murakami, M. Yaoita, Y. Aoki, M. Koyama Tags: Abstracts Source Type: research
Paternal uniparental disomy with segmental loss of heterozygosity of chromosome 11 are hallmark characteristics of syndromic and sporadic embryonal rhabdomyosarcoma
In this study, we are able to clearly demonstrate complete UPD11 in both syndromic and sporadic ERMS. © 2016 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - August 31, 2016 Category: Genetics & Stem Cells Authors: Katherine M. Robbins, Deborah L. Stabley, Jennifer Holbrook, Rebecca Sahraoui, Alexa Sadreameli, Katrina Conard, Laura Baker, Karen W. Gripp, Katia Sol ‐Church Tags: Original Article Source Type: research
Mid-Ventricular Obstructive Hypertrophic Cardiomyopathy Associated with an Apical Aneurysm in Costello Syndrome: A Case Report
In this report, we present a 28-yaers-old female patient with hypertrophic cardiomyopathy, clinically and genetically diagnosed with Costello syndrome. Echocardiography showed hypertrophic cardiomyopathy with mid-ventricular obstruction (Figure) and an apical aneurysm. (Source: Journal of Cardiac Failure)
Source: Journal of Cardiac Failure - August 24, 2016 Category: Cardiology Authors: Masahiro Uchimura, Takahiro Sakamoto, Shimpei Ito, Taiji Okada, Takeshi Ouchi, Nobuhide Watanabe, Akihiro Endo, Kazuaki Tanabe Source Type: research
Cardiac Manifestations and Associations with Gene Mutations in Patients Diagnosed with RASopathies
AbstractRASopathies are a group of syndromes caused by germline mutations of the RAS/MAPK pathway. They include Noonan syndrome, cardio-facio-cutaneous syndrome, Costello syndrome, and Noonan syndrome with multiple lentigines, which share many characteristic features including cardiac abnormalities. Here, we retrospectively reviewed the clinical manifestations and evaluated the genotype –phenotype associations with special focus on cardiac lesions of the patients with RASopathies. Cardiac symptoms were the most common initial presentation (27 %), except for admission to neonatal intensive care. Although there was a sign...
Source: Pediatric Cardiology - August 22, 2016 Category: Cardiology Source Type: research
The Splicing Efficiency of Activating HRAS Mutations Can Determine Costello Syndrome Phenotype and Frequency in Cancer
by Anne-Mette Hartung, Jeff Swensen, Inaki E. Uriz, Morten Lapin, Karen Kristjansdottir, Ulrika S. S. Petersen, Jeanne Mari V. Bang, Barbara Guerra, Henriette Skovgaard Andersen, Steven F. Dobrowolski, John C. Carey, Ping Yu, Cecily Vaughn, Amy Calhoun, Martin R. Larsen, Lars Dyrskjøt, David A. Stevenson, Brage S. Andresen
Costello syndrome (CS) may be caused by activating mutations in codon 12/13 of the HRAS proto-oncogene. HRAS p.Gly12Val mutations have the highest transforming activity, are very frequent in cancers, but very rare in CS, where they are reported to cause a severe, early lethal, phenotype. We identified ...
Source: PLoS Genetics - May 18, 2016 Category: Genetics & Stem Cells Authors: Anne-Mette Hartung Source Type: research
Objective studies of the face of Noonan, Cardio ‐facio‐cutaneous, and Costello syndromes: A comparison of three disorders of the Ras/MAPK signaling pathway
In this study, subjective observations, in the main, were validated by anthropometry with one exception. In individuals with Costello syndrome, mouth width was normal, thus the impression of wide mouth is likely due to full lips or the mouth being viewed in relation to a narrow lower face. When the three conditions were compared objectively, syndrome‐specific pattern profiles showed high concordance in early life. At older ages, Cardio‐facio‐cutaneous syndrome was distinguished by increased width of the mid/lower face, and reduced growth of maxillary and mandibular dimensions was noted in both Noonan and Costello syn...
Source: American Journal of Medical Genetics Part A - May 6, 2016 Category: Genetics & Stem Cells Authors: Judith E. Allanson Tags: Original Article Source Type: research
The Fourth International Symposium on Genetic Disorders of the Ras/MAPK pathway
This report summarizes the proceedings of the 4th International Symposium on Genetic Disorders of the Ras/MAPK pathway and highlights gaps in the field. © 2016 Wiley Periodicals, Inc. (Source: American Journal of Medical Genetics Part A)
Source: American Journal of Medical Genetics Part A - May 6, 2016 Category: Genetics & Stem Cells Authors: David A. Stevenson, Lisa Schill, Lisa Schoyer, Brage S. Andresen, Annette Bakker, Pinar Bayrak‐Toydemir, Emma Burkitt‐Wright, Kathryn Chatfield, Florent Elefteriou, Ype Elgersma, Michael J. Fisher, David Franz, Bruce D. Gelb, Anne Goriely, Karen W. Gr Tags: Conference Report Source Type: research
