Cardiofacial Syndrome Research Articles

The surgical treatment of velopharyngeal insufficiency in patients with velo cardio facial syndrome

The surgical treatment of velopharyngeal insufficiency in patients with velo cardio facial syndrome

Cayler Cardio-Facial Syndrome: A Rare Case Report

Background: Cayler cardio-facial syndrome is a rare syndrome characterised by asymmetric crying facies with congenital heart defects. Syndrome may be associated with other dysmorphic features and systemic anomalies. Case Report: We report the clinical observation of a 04 years old boy presenting with Cayler cardio-facial syndrome.

Aggressive posterior retinopathy of prematurity in baby showing features of cardiofacial syndrome overlapping with pearl syndrome

We report the case of a preterm infant referred to us for retinopathy of prematurity (ROP) screening at postmenstrual age of 35 weeks who presented with right-sided congenital lower motor neuron type facial nerve palsy, lagophthalmos, normal anterior segment findings, and aggressive posterior ROP on the fundus examination in both eyes. Right-sided microtia, normal left ear, and asymmetric crying facies were noted. The baby received intravitreal bevacizumab 0.625 mg in both eyes after systemic workup which revealed a ventricular septal defect with patent ductus arteriosus and normal brain magnetic resonance imaging. At 2 months postinjection, the plus disease decreased significantly with vessels developing up to zone 3 with no ROP in both the eyes.

СЛУЧАЙ ВРОЖДЁННОЙ АТРЕЗИИ ХОАН У РЕБЁНКА С ПЕРВИЧНЫМ ИММУНОДЕФИЦИТОМ (СИНДРОМ ДИ ДЖОРДЖИ)

Congenital atresia of the choanas (CVC) is a violation of the patency of the nasal cavity associated with its complete or partial infection of the connective, cartilage or bone tissue. CVC is a consequence of the preservation of the nasal palatine membrane, which occurs between the 6th and 12th weeks of gestation, due to the approach and successive fusion of the posterior edge of the opener with the posterior ends of the nasal concha. According to domestic and foreign literature, for 5000-7000 newborns there is 1 observation of CVC, the population frequency of congenital malformations in individual countries ranges from 2.7 to 16.3%. The deletion syndrome of the 22nd chromosome, described as Dee Georgi syndrome or cyclic cardiofacial syndrome, is a combination of morphological, immunological and neurological changes that are the result of a deletion of the long arm of 1 copy of the 22nd chromosome - del 22q11.2. In the classical concept, this syndrome is a triad consisting of congenital heart disease, thymus hypoplasia (aplasia) and hypocalcemia, as a result of parathyroid hypoplasia. Dee Georgi - syndrome (SDD) or the case of the 22nd chromosome is the most common problem among other mutations in the human genome, it is second only to Down syndrome, trisomy on the 21st chromosome. The frequency of occurrence varies from 1: 4000 to 1: 6000 newborns. This review seeks to assess the factors that influence the outcome of transnasal endoscopic restoration of the congenital atresia of the choan. The article presents a method for eliminating congenital atresia of the choan in a child with Dee Georges syndrome with transeptal access.

Rare Association of Congenital Facial Palsy, Bilateral Microtia and Congenital Heart Disease

We report a case of a two day old female child with congenital facial palsy, bilateral microtia, congenital heart disease, renal ectopia and unilateral hypoplasia of depressor anguli oris muscle. These constellation of symptoms have not been found together in any case before. This unknown syndrome could be considered to be in a gray zone between Caylers Cardiofacial syndrome and Pearls syndrome.

Rare Association of Bilateral Anotia with Congenital Facial Palsy

Anotia is a birth defect and is associated with facial palsy and congenital heart defect as various presentation of cardiofacial syndrome. Herein we report a case of bilateral anotia and unilateral congenital facial palsy without congenital heart disease. It may occur due to single gene abnormality, teratogenic effect of maternal ingestion of thalidomide, retinoic acid, misoprostol or maternal diabetes, dietary lack of carbohydrates and folate.J Nepal Paediatr Soc 2015;35(2):195-197

Colonic Adenocarcinoma in a Patient with Velo Cardio Facial Syndrome (VCFS) and 22q11.2 Microdeletion

Colonic Adenocarcinoma in a Patient with Velo Cardio Facial Syndrome (VCFS) and 22q11.2 Microdeletion Colorectal cancer (CRC) is one of the most common cancers and second most common cause of cancer related mortality. Chromosomal instability and microsatellite instability have long been considered as major factors in the etiology of colon cancer. Chromosome 22q losses have been reported both in primary and metastatic CRC. Chromosome 22q11.2 microdeletion syndrome is an umbrella term that encompasses various phenotypes, and is the most common microdeletion syndrome in humans. We report an uncommon association of colon cancer in a patient with VCFS and 22q11.2 microdeletion. While this finding may be coincidental, it is important to further evaluate patients with CRC and 22q11.2 microdeletion to assess if this association is more frequent than has been reported.

Cayler cardiofacial syndrome with situs inversus totalis

Cayler cardiofacial syndrome is characterised by congenital unilateral hypoplasia of the depressor anguli oris muscle (DAOM) in association with congenital cardiac defects. Hypoplasia of this muscle causes inability to move one corner of the mouth downward and outward while crying or grimacing, giving rise to an 'asymmetric crying face' appearance. A variety of congenital cardiac defects have been described. Occasionally, other organ system anomalies may be additionally present. We present an instance of right-sided hypoplasia of the DAOM in a male newborn, which additionally had dextrocardia as a component of situs inversus totalis. To our knowledge, situs inversus totalis has not been previously documented as a part of this syndrome. Additionally, we reiterate that paediatricians need to be aware that this minor facial anomaly may be associated with severe internal organ system anomalies, with cardiac being most common.

Congenital Pharyngo-oto-cutaneous Fistula<subtitle>Surgical Management of an Unusual Anomaly of the First Branchial Apparatus</subtitle>

First branchial anomalies embody a small subset of congenital malformations of the head and neck. Classically, they are duplication abnormalities of the external auditory canal (EAC) and can involve the middle ear and parotid gland. Herein, we describe a 5-yearold girl with unilateral microtia, autism, and Cayler cardiofacial syndrome (asymmetric crying facies and congenital heart disease). She also had a congenital pharyngo-oto-cutaneous fistula resulting in high-volume otorrhea of saliva and formula. We present our experience with surgical correction of this unique condition. To our knowledge, this is the first reported case of a congenital pharyngo-oto-cutaneous fistula involving a derangement of all 3 germ layers of the first branchial apparatus.

Intellectual abilities in a large sample of children with Velo–Cardio–Facial Syndrome: an update

Learning disabilities are one of the most consistently reported features in Velo-Cardio-Facial Syndrome (VCFS). Earlier reports on IQ in children with VCFS were, however, limited by small sample sizes and ascertainment biases. The aim of the present study was therefore to replicate these earlier findings and to investigate intellectual abilities in a large sample of children with VCFS. In addition, we aimed to identify factors that may contribute to within-syndrome variability in cognitive performance, such as the mode of inheritance of the deletion, sex, the presence of a heart defect and psychiatric morbidity. IQ data of 103 children with VCFS (56 males, 47 females) were collected. Psychiatric diagnosis was additionally recorded. Children with VCFS had a mean full-scale IQ (FSIQ) of 73.48 (range: 50-109). There were no effects of sex, presence of a heart defect and psychiatric condition on intellectual profile. Inheritance of the deletion affected cognitive performance in VCFS, with children with familial deletions having significant lower FSIQ than children with a de novo deletion. Learning disabilities are very common in children with VCFS, although marked within syndrome variability is noted. One factor contributing to this variability seems to be the mode of inheritance of the deletion.

Velo–Cardio–Facial Syndrome: A Model for Understanding Microdeletion Disorders

Velo–Cardio–Facial Syndrome: A Model for Understanding Microdeletion Disorders

22q11 microdeletion studies in the heart tissue of an abortus involving a familial form of congenital heart disease

Microdeletion of chromosome 22 is responsible for DiGeorge syndrome, Velo Cardio Facial syndrome, and conotruncal defects. Here, we report on a case of microdeletion 22q11.2 in the heart tissue of a miscarried fetus in a family whose two children had died due to complex congenital heart disease. Fluorescence in situ hybridization (FISH) analysis in the couple revealed that the mother was mosaic for microdeletion of chromosome 22q11.2 in 10% of her peripheral lymphocytes. Prenatal diagnosis was offered to her in her third pregnancy. On routine ultrasonography at 10 weeks, the overall view of the heart was normal. However, before any further tests could be performed, she miscarried at 16 weeks. FISH studies on the heart tissue of the abortus revealed 22q11.2 microdeletion with two different cell lines. This suggests the importance of performing FISH studies when there is a history of congenital heart disease, even though ultrasonography shows a normal view of the heart.

Anotia and facial palsy: unusual features of cardiofacial syndrome

Anotia and facial palsy: unusual features of cardiofacial syndrome

The behavioural phenotype in velo-cardio-facial syndrome.

Velo—cardio—facial syndrome (VCFS), the most frequent known interstitial deletion found in humans, occurs with an incidence of approx 1/4000 live births (1). VCFS is associated with chromosomal microdeletions in the ql l band of chromosome 22 in over 90% of those with the disorder (2). The VCFS phenotype is complex, with multiple congenital abnormalities affecting a wide range of tissues and organs, often occurring in different combinations and with widely differing severity. Although in excess of 100 phenotypic features have been described, the most common include characteristic dysmorphology, congenital heart disease, cleft palate, borderline learning disability, and psychiatric disorder (Fig. 1). Variability in phenotypic expression has resulted in the same deletion being linked to several syndromes including DiGeorge syndrome, conotruncal anomaly face syndrome, Cayler syndrome, and Opitz GBBB syndrome, and the term “22q11 deletion syndrome” has been proposed as a replacement term for these other designators.

EYA1 Mutation in a Newborn Female Presenting with Cardiofacial Syndrome

The combination of an asymmetric crying face and heart defect has been termed cardiofacial syndrome. This "syndrome" is etiologically heterogeneous and a subset of patients have 22q111.2 deletions. We present a female with Cayler's cardiofacial syndrome phenotype who had a frameshift mutation of the EYA1 gene. We conclude that EYA1 mutation represents a previously undescribed cause of cardiofacial syndrome.

Three New Patients With Congenital Unilateral Facial Nerve Palsy due to Chromosome 22q11 Deletion

We report three unrelated patients with congenital facial nerve palsy and chromosome 22q11 deletion, a condition hitherto poorly recognized. In the first case, facial palsy was associated with aortic coarctation, ductus arteriosus, and ostium secundum atrial septal defect. In the second case, facial palsy was associated with ostium secundum atrial septal defect, obstruction of the ureteropelvic junction, double ureteropelvic-calicial system, and distal metaphyseal widening of the forearm and leg bones. In both cases, facial palsy was the presenting feature. In the third case, an ostium secundum atrial septal defect was also present, but involvement of cranial nerves III, VI, and VIII, in addition to hypoplastic structures of cerebellar and cerebral peduncles, were the predominant features. There were no inherited deletions within chromosome band 22q11 and the de novo deletions detected in each case belonged to the paternally derived chromosome 22. Association of facial nerve palsy and congenital heart disease versus cardiofacial syndrome are different only on clinical grounds, so both conditions can be genetically identical and form part of the spectrum of defects associated with chromosome 22q11 deletions. We recommend investigation for chromosome 22q11 deletions in patients with complete nerve facial palsy.

Polymorphism in SNAP29 gene promoter region associated with schizophrenia

Linkage studies indicate that chromosome 22q contains a locus, or loci, for schizophrenia (SZ) and bipolar disorder (BPD). Furthermore, the congenital disorder velo cardio facial syndrome (VCFS), which is usually caused by a 22q11 microdeletion, is associated with an increased prevalence of psychiatric disease, including SZ and BPD. One plausible candidate gene that maps to 22q11, in a region deleted in the most common form of VCFS, is SNAP29, a member of the SNAP-25 family of SNARE proteins. To search for possible functional mutations in SNAP29 that could be analyzed as candidates for 22q11-linked psychiatric problems, exons, intron-exon junctions and the promoter region were screened. No coding variants were found, although a silent mutation at codon 6 and three single nucleotide polymorphisms (SNPs) were identified in the 5' untranslated and promoter regions. One SNP, an A-->G transition 923 [corrected] nucleotides upstream of the transcription start site, showed a moderately significant difference in the distribution of alleles and genotypes in patients with SZ compared with controls (allele frequency: chi(2) = 5.57, 1 df, P = 0.018; genotype: chi(2) = 9.49, 2 df, P = 0.009; odds ratio = 1.59, 95% Cl = 1.08--2.34). No significant difference was found in patients with BPD. Although the functional significance of this mutation is not known, the tetranucleotide core sequence of the ets and IK2 families of transcription factors is altered as a result of the SNP. These data suggest that a mutation in the SNAP29 gene promoter region, or a mutation in linkage disequilibrium with the promoter SNP, may be involved in the pathogenesis of chromosome 22-linked SZ.

Phenotype of the 22q11.2 deletion in individuals identified through an affected relative: Cast a wide FISHing net!

PurposeThe chromosome 22q11.2 deletion has been identified in the majority of patients with DiGeorge syndrome, velocardiofacial syndrome, and conotruncal anomaly face syndrome and in some patients with the autosomal dominant Opitz G/BBB syndrome and Cayler cardiofacial syndrome. In addition, 22q11.2 deletion studies are becoming part of a standardized diagnostic workup for some isolated defects such as conotruncal cardiac anomalies and velopharyngeal incompetence. However, there is little information available on the clinical findings of unselected patients. For example, those individuals identified during prenatal diagnosis, as part of a generalized screening protocol, or following the diagnosis in a relative. This information will be invaluable in defining the variability of the disorder and in observing long-term outcome in the absence of targeted remediations. This study allows one to examine the first unselected cohort of patients and serves to highlight the importance of deletion testing in parents of affected probands. MethodsThirty individuals with a 22q11.2 deletion were identified following the diagnosis in a relative. Nineteen were adults ascertained only following the diagnosis in their child, 10 were children identified following the diagnosis in their sibling, and one was a child diagnosed prenatally following the diagnosis in her parent. ResultsSixty percent of patients had no visceral anomalies. In fact, only 6 of the 19 adults (32%) and 6 of the 11 children (55%) had major findings which would have brought them to medical attention. Deletion sizing demonstrated the same large 3–4MB deletion in most families despite wide inter and intrafamilial variability and there was no difference in clinical findings based on the parent of origin. Thus, no genotype-phenotype correlations could be made. ConclusionWe report the first unselected cohort of patients with the 22q11.2 deletion identified through an affected relative. Analysis of this series of 30 patients, many with very mild manifestations of the deletion, allows one to examine the outcome in individuals who lacked specific remediations for this disorder. It emphasizes the importance of broadening the index of suspicion in order to provide appropriate recurrence risk counseling, cognitive remediation, and medical management. Further, it underscores the lack of familial concordance and the current lack of genotype-phenotype correlations in this disorder, and it raises the possibility that the deletion is more common than previously reported.

Deletion of 150 kb in the minimal DiGeorge/velocardiofacial syndrome critical region in mouse.

Deletions or rearrangements of human chromosome 22q11 lead to a variety of related clinical syndromes such as DiGeorge syndrome (DGS) and velo--cardiofacial syndrome (VCFS). In addition, patients with 22q11 deletions have an increased incidence of schizophrenia and several studies have mapped susceptibility loci for schizophrenia to this region. Human molecular genetic studies have so far failed to identify the crucial genes or disruption mechanisms that result in these disorders. We have used gene targeting in the mouse to delete a defined region within the conserved DGS critical region (DGCR) on mouse chromosome 16 to prospectively investigate the role of the mouse DGCR in 22q11 syndromes. The deletion spans a conserved portion ( approximately 150 kb) of the proximal region of the DGCR, containing at least seven genes ( Znf74l, Idd, Tsk1, Tsk2, Es2, Gscl and Ctp ). Mice heterozygous for this deletion display no findings of DGS/VCFS in either inbred or mixed backgrounds. However, heterozygous mice display an increase in prepulse inhibition of the startle response, a manifestation of sensorimotor gating that is reduced in humans with schizophrenia. Homozygous deleted mice die soon after implantation, demonstrating that the deleted region contains genes essential for early post-implantation embryonic development. These results suggest that heterozygous deletion of this portion of the DGCR is sufficient for sensorimotor gating abnormalities, but not sufficient to produce the common features of DGS/VCFS in the mouse.

UFD1L and CDC45L: a role in DiGeorge syndrome and related phenotypes?

Molecular genetics is contributing to the understanding of normal and abnormal cardiovascular development and morphogenesis. Deletions of chromosome 22q11.2 have been associated with distinct phenotypes that result from a failure to form derivatives of third and fourth branchial arches, including DiGeorge syndrome (DGS) and velo–cardio–facial syndrome (VCFS). The biochemical mechanisms underlying these phenotypes remain undetermined. A recent study provides new insight into the mechanism by which gene deletions produce the DGS and VCFS phenotypes.