scholarly journals Prenatal Sonographic Features of CHARGE Syndrome

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 415
Author(s):  
Kuntharee Traisrisilp ◽  
Wisit Chankhunaphas ◽  
Rekwan Sittiwangkul ◽  
Chureerat Phokaew ◽  
Vorasuk Shotelersuk ◽  
...  
Keyword(s):  
De Novo ◽  
Heart Defects ◽  
Molecular Genetic ◽  
Choanal Atresia ◽  
Charge Syndrome ◽  
Acoustic Stimulation ◽  
Genetic Mutation ◽  
Suspected Case ◽  
Autosomal Dominant Disorder ◽  
Canal Stenosis

CHARGE syndrome is a rare autosomal dominant disorder, associated with coloboma (C), heart defects (H), choanal atresia (A), retardation of growth and/or central nervous system (R), genitourinary anomalies (G) and ear abnormalities (E). Prenatal diagnosis of the syndrome is very rare but may be suspected when a combination of such abnormalities is identified. We describe a prenatally suspected case of CHARGE syndrome due to unique findings of cardiac defects (DORV) in combination with minor clues, including a structurally malformed ear with persistent non-response to an acoustic stimulation (which has never been prenatally described elsewhere), renal malrotation and growth restriction. Postnatal diagnosis was made based on confirmation of the prenatal findings and additional specific findings of bilateral coloboma, choanal atresia and ear canal stenosis. Finally, molecular genetic testing by whole exome sequencing of the neonate and her parents revealed a novel de novo heterozygous frameshift c.3506_3509dup variant in the CHD7 gene, confirming the clinical diagnosis of CHARGE syndrome. In conclusion, we describe unique prenatal features of CHARGE syndrome. Educationally, this is one of the rare examples of CHARGE syndrome, comprising all of the six specific anomalies as originally described; it is also supported by the identification of a specific genetic mutation. The identified genetic variant has never been previously reported, thereby expanding the mutational spectrum of CHD7. Finally, this case can inspire prenatal sonographers to increase awareness of subtle or minor abnormalities as genetic sonomarkers.

Charge Syndrome

2018 ◽  
Author(s):  
Pilar Mercado ◽  
Jamey E. Eklund ◽  
Jennifer L. Anderson
Keyword(s):  
Cranial Nerve ◽  
De Novo ◽  
Heart Defects ◽  
Choanal Atresia ◽  
Semicircular Canals ◽  
Charge Syndrome ◽  
Chromosome 8 ◽  
De Novo Mutation ◽  
Diagnostic Features ◽  
Equal Distribution

The major diagnostic features of CHARGE syndrome include coloboma of the eyes, choanal atresia or stenosis, distinctive external ears, cranial nerve abnormalities, and absent or small semicircular canals. The mnemonic refers to coloboma of the eye, heart defects, atresia of choanae, retardation of growth and development, cenitalia hypoplasia, and ear abnormalities and deafness. There is no defined etiology, though a de novo mutation on the CHD 7 gene located on Chromosome 8 is responsible for more than 50% of CHARGE cases. The incidence of CHARGE is about 1:10,000 live births with an equal distribution between males and females. The anesthetic implications of this syndrome are many and vary with the patient’s phenotype. A potential difficult airway, congenital heart defects, choanal atresia, and cranial nerve abnormalities present the most significant issues for the anesthesiologist. A multidisciplinary team must be established early to properly care for these complex patients.

scholarly journals De Novo Duplication in the CHD7 Gene Associated With Severe CHARGE Syndrome

2019 ◽  
Vol 12 ◽  
pp. 117863101983901 ◽  
Author(s):  
Laura Pranckėnienė ◽  
Eglė Preikšaitienė ◽  
Lucie Gueneau ◽  
Alexandre Reymond ◽  
Vaidutis Kučinskas
Keyword(s):  
Umbilical Hernia ◽  
Developmental Disorder ◽  
Autosomal Dominant ◽  
De Novo ◽  
Choanal Atresia ◽  
Sensory System ◽  
Charge Syndrome ◽  
Linea Alba ◽  
Congenital Hernia ◽  
Chd7 Gene

CHARGE syndrome is an autosomal dominant developmental disorder associated with a constellation of traits involving almost every organ and sensory system, in particular congenital anomalies, including choanal atresia and malformations of the heart, inner ear, and retina. Variants in CHD7 have been shown to cause CHARGE syndrome. Here, we report the identification of a novel de novo p.Asp2119_Pro2120ins6 duplication variant in a conserved region of CHD7 in a severely affected boy presenting with 3 and 5 of the CHARGE cardinal major and minor signs, respectively, combined with congenital umbilical hernia, congenital hernia at the linea alba, mildly hypoplastic inferior vermis, slight dilatation of the lateral ventricles, prominent metopic ridge, and hypoglycemic episodes.

scholarly journals A Rare Case of Vascular Ring and Coarctation of the Aorta in Association with CHARGE Syndrome

2017 ◽  
Vol 44 (2) ◽  
pp. 138-140
Author(s):  
Jonathan B. Wagner ◽  
Joshua Q. Knowlton ◽  
Peter Pastuszko ◽  
Sanket S. Shah
Keyword(s):  
Aortic Arch ◽  
Rare Case ◽  
Heart Defects ◽  
Genetic Disorder ◽  
Vascular Ring ◽  
Choanal Atresia ◽  
Coarctation Of The Aorta ◽  
Charge Syndrome ◽  
Rare Type ◽  
Aortic Arch Anomaly

A male neonate presented with CHARGE syndrome, a multiorgan genetic disorder involving the Coloboma of the eyes, congenital Heart defects, nasal choanal Atresia, growth and development Retardation, Genitourinary disorders, and Ear anomalies and deafness. Moreover, he had a rare case of vascular ring—consisting of a right aortic arch with retroesophageal brachiocephalic artery—combined with coarctation of the mid-aortic arch. He underwent both vascular ring and aortic arch repair at our institution. To our knowledge, this is the 4th documented case of this exceedingly rare type of aortic arch anomaly combined with aortic arch obstruction. Moreover, it is the first confirmed case of these combined disorders occurring in CHARGE syndrome. This report describes a truly rare case and reveals the limitations of echocardiography in detecting complex aortic arch anomalies while illustrating the benefits of advanced imaging prior to surgical intervention.

scholarly journals Prenatal Sonographic and Molecular Genetic Diagnosis of Popliteal Pterygium Syndrome

Diagnostics ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1819
Author(s):  
Kuntharee Traisrisilp ◽  
Suchaya Luewan ◽  
Sirinart Sirilert ◽  
Phudit Jatavan ◽  
Theera Tongsong
Keyword(s):  
Cleft Lip ◽  
De Novo ◽  
Molecular Genetic ◽  
Genetic Diagnosis ◽  
Ambiguous Genitalia ◽  
Knee Extension ◽  
Lower Limbs ◽  
Autosomal Dominant Disorder ◽  
Popliteal Pterygium Syndrome ◽  
Popliteal Pterygium

Popliteal pterygium syndrome (PPS) is an extremely rare autosomal dominant disorder, characterized by the cleft palate with or without cleft lip, limbs abnormalities with highly characteristic features of popliteal webbing, syndactyly, and genital abnormalities and nail anomalies. Prenatal diagnosis of PPS has been extremely rare. We describe a unique case of fetal PPS at 20 weeks of gestation. The diagnosis of PPS was based on the ultrasound findings of bilateral popliteal webbings, extending from posterior aspects of the upper thighs through the lower legs, resulting in restriction in knee extension, bilateral equinovarus feet with syndactyly, ambiguous genitalia and the grooved lip. Anatomical structures were otherwise normal. Trio whole-exome sequencing revealed a de novo heterozygous IRF6 gene mutation in the fetus, confirming the diagnosis with PPS. In conclusion, popliteal webbing or combination of facial cleft or cleft variants and bilateral abnormal postures of the lower limbs is suggestive of PPS and genetic diagnosis should be warranted.

scholarly journals A Japanese Patient with Genitopatellar Syndrome Transiently Presenting with Cardiac Intramural Cavity during the Neonatal Period

2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Kiichi Takahashi ◽  
Hiroyuki Adachi ◽  
Manatomo Toyono ◽  
Masato Ito ◽  
Akie Kato ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
De Novo ◽  
Heart Defects ◽  
Ductus Arteriosus ◽  
Renal Cysts ◽  
Ventricular Septal Defects ◽  
Autosomal Dominant Disorder ◽  
Septal Defects ◽  
Pathogenic Variants

Genitopatellar syndrome (GPS) is a rare autosomal dominant disorder caused by de novo pathogenic variants in the KAT6B gene. It is characterized by genital abnormalities, patellar hypoplasia/agenesis, flexion contractures of the hips and knees, corpus callosum agenesis with microcephaly, and hydronephrosis and/or multiple renal cysts. More than half of patients with GPS have congenital heart defects, mostly atrial and/or ventricular septal defects, patent foramen ovale, and patent ductus arteriosus. We report a case of a Japanese neonate with a de novo heterozygous c.3769_3772delTCTA pathogenic variant in the KAT6B gene who presented with a cardiac intramural cavity of the ventricular septum at birth. The cavity unexpectedly disappeared at 1 month of age, but trabecular septal thinning and flash remained. The features of the cavity were not consistent with those of congenital ventricular diverticulum or aneurysm, and its identity and prognosis are still unclear. Because patients with GPS may exhibit various forms of cardiac malformation, careful cardiac examination and follow-up are required from birth in cases of suspected GPS.

Novel TSC1 mutation associated with variable phenotypes in tuberous sclerosis

2013 ◽  
Vol 154 (23) ◽  
pp. 914-918 ◽  
Author(s):  
Erzsébet Kövesdi ◽  
Kinga Hadzsiev ◽  
Katalin Komlósi ◽  
Mária Kassay ◽  
Péter Barsi ◽  
...  
Keyword(s):  
Tuberous Sclerosis ◽  
De Novo ◽  
Phenotypic Variability ◽  
Molecular Genetic ◽  
Clinical Signs ◽  
Renal Cysts ◽  
Molecular Genetic Analysis ◽  
Autosomal Dominant Disorder ◽  
Modifying Factors ◽  
Tsc1 Gene

Tuberous sclerosis is an autosomal dominant disorder, caused by mutations of the TSC1 or TSC2 genes resulting in tumor predisposition. Clinical signs include non-malignant brain tumors, skin, eye, heart and kidney abnormalities. The authors report a Hungarian family with broad phenotypic variability. First, the 5-year-old boy, showing the most symptoms was examined, whose first seizure occurred at 15 months and a cranial magnetic resonance imaging revealed numerous intracerebral calcareous foci. Except of hypopigmented skin spots, no other abnormality was found on physical examination. The mother was completely asymptomatic. Epilepsy of the maternal uncle started at the age of 3 years, of his sister at the age of 17 years and of the maternal grandmother at the age of 39 years. At the age of 52 years the grandmother developed renal cysts. Molecular genetic analysis of the family confirmed a de novo heterozygous point mutation (c.2523 C\>T) in exon 20 of the TSC1 gene. The mutation was detected in all examined family members. Despite increasing data on the pathomechanism of tuberous sclerosis, there is still little known about the genetic modifying factors influencing the broad intra- and interfamilial phenotypic variability. Orv. Hetil., 2013, 154, 914–918.

scholarly journals Three Novel Mutations of CHD7 Gene in Two Turkish Patients with Charge Syndrome; A Double Point Mutation and an Insertion

2015 ◽  
Vol 18 (1) ◽  
pp. 65-70
Author(s):  
Ozlem Giray Bozkaya ◽  
E. Ataman ◽  
C. Randa ◽  
D. Onur Cura ◽  
S. Gürsoy ◽  
...  
Keyword(s):  
Genetic Disease ◽  
Double Point ◽  
Heart Defects ◽  
Choanal Atresia ◽  
Charge Syndrome ◽  
Dna Binding Protein ◽  
The Other ◽  
Novel Mutations ◽  
Chd7 Gene ◽  
Turkish Patients

Abstract The CHARGE (coloboma, heart defects, atresia, retardation, genital, ear) syndrome is a genetic disease characterized by ocular coloboma, choanal atresia or stenosis and semicircular canal abnormalities. Most of the patients clinically diagnosed with CHARGE syndrome have mutations in chromodomain helicase DNA-binding protein 7 (CHD7) gene. The CHD7 gene is located on chromosome 8q12.1, and up to now, there are more than 500 pathogenic mutations identified in the literature. We report two patients diagnosed with CHARGE syndrome with two novel mutations in the CHD7 gene: the first patient has double consecutive novel mutations in three adjacent codons, and the other has a novel insertion.

scholarly journals Two cases of deletion 2q37 associated with segregation of an unbalanced translocation 2;21: choanal atresia leading to misdiagnosis of CHARGE syndrome

2009 ◽  
Vol 160 (4) ◽  
pp. 711-717 ◽  
Author(s):  
Eduardo Fernández-Rebollo ◽  
Olga Pérez ◽  
Cristina Martinez-Bouzas ◽  
Maria Carmen Cotarelo-Pérez ◽  
Intza Garin ◽  
...  
Keyword(s):  
Phenotypic Variability ◽  
Molecular Genetic ◽  
Choanal Atresia ◽  
Underlying Mechanism ◽  
Charge Syndrome ◽  
Genetic Studies ◽  
The Family ◽  
Proper Diagnosis ◽  
Dependent Probe

ContextThe phenotypic variability of patients with syndromes presenting with dysmorphism makes clinical diagnosis difficult, leading to an exhaustive genetic study to determine the underlying mechanism so that a proper diagnosis could be established.ObjectiveTo genetically characterize siblings, the older sister diagnosed with Albright hereditary osteodystrophy and the younger one with CHARGE syndrome.DesignClinical case report.MethodsClinical, biochemical, and radiological studies were performed on the family. In addition, molecular genetic studies including sequencing of GNAS, typing of microsatellites on 2q and 21q, and multiplex ligation-dependent probe amplification of subtelomeric regions were performed, as well as confirmatory fluorescent in situ hybridization analysis.ResultsThe genetic analysis revealed that both sisters presented a 2q37 deletion due to the maternal unbalanced segregation of a 2;21 translocation.ConclusionsThis is the first report of a 2q37 deletion where differential diagnosis of CHARGE syndrome is needed due to the appearance of choanal atresia.

Skull Base Anatomy in Patients with Bilateral Choanal Atresia: A Radiographic Study

2021 ◽  
Author(s):  
Christopher Pool ◽  
Einat Slonimsky ◽  
Roshan Nayak ◽  
Lisa Engle ◽  
Junjia Zhu ◽  
...  
Keyword(s):  
Congenital Anomaly ◽  
Skull Base ◽  
Congenital Anomalies ◽  
Heart Defects ◽  
Choanal Atresia ◽  
Retrospective Chart Review ◽  
Charge Syndrome ◽  
The Face ◽  
Skull Base Anatomy ◽  
Skull Base Defects

Abstract Background The risk of skull base injury during choanal atresia repair can be mitigated via thorough understanding of skull base anatomy. There is a paucity of data describing differences in skull base anatomy between patients with coloboma, heart defects, atresia choanae, growth retardation, genital abnormalities, and ear abnormalities (CHARGE) syndrome and those without. Objectives The aim of this study was to measure nasal and skull base anatomy in patients with isolated bilateral choanal atresia (BCA), CHARGE syndrome, and other syndromic congenital anomalies. Methods Retrospective chart review of patients with bilateral choanal atresia and computed tomography of the face between 2001 and 2019 were evaluated. Choanal width, height, mid-nasal height, and skull base slope were measured radiographically. Differences in anatomy between healthy patients, those with CHARGE syndrome, and those with other congenital anomalies were compared. Results Twenty-one patients with BCA and relevant imaging were identified: 7 with isolated BCA, 6 with CHARGE syndrome, and 8 with other congenital anomalies. A t-test indicated insignificant difference in skull base slope, choanal height, choanal width, or mid-nasal skull base height between isolate BCA cases and patients with any congenital anomaly. When comparing CHARGE to isolated BCA cases, mid-nasal height was shorter in CHARGE patients (p = 0.03). There were no differences in measurements between patients with congenital anomalies excluding CHARGE (p > 0.05). Two patients in the congenital anomaly group were found to have bony skull base defects preoperatively. Conclusion This study represents the largest description of skull base and nasal anatomy in patients with CHARGE syndrome and BCA. Surgeons should be aware of the lower skull base in CHARGE patients to avoid inadvertent skull base injury.

scholarly journals De novo SCN1A géndeletio terápiarezisztens Dravet-szindrómában

2015 ◽  
Vol 156 (49) ◽  
pp. 2009-2012 ◽  
Author(s):  
Judit Bene ◽  
Kinga Hadzsiev ◽  
Katalin Komlósi ◽  
Erzsébet Kövesdi ◽  
Petra Mátyás ◽  
...  
Keyword(s):  
Copy Number ◽  
De Novo ◽  
Genetic Test ◽  
Molecular Genetic ◽  
Copy Number Variations ◽  
Sequencing Analysis ◽  
Loss Of Function ◽  
Autosomal Dominant Disorder ◽  
Molecular Genetic Test ◽  
Scn1a Gene

Severe myoclonic epilepsy in infancy (Dravet’s syndrome) is a very rare form of epilepsy. Mutations of SCN1A gene encoding voltage-gated sodium channel alpha-1 subunit are major causes of the autosomal dominant disorder. Most cases are associated with a de novo point mutation, but some patients have copy number variations. The protein encoded by the SCN1A gene plays a role in the generation and propagation of action potentials. Loss of function caused by the majority of gene mutations leads to hyperexcitability of the neuronal network that finally results in the formation of the epileptic seizures. Molecular genetic test for copy number variations of SCN1A gene is available in the department of the authors since 2013 besides sequencing analysis of the whole gene. This article presents the case of a 7-year-old patient with two years of recorded patient history outside of the author’s department. Molecular genetic test, which detected a de novo SCN1A gene deletion in heterozygous form, revealed SCN1A gene associated monogenic epileptic syndrome being in the genetic background of therapy-resistant seizures. Orv. Hetil., 2015, 156(49), 2009–2012.

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