The impact of concurrent X chromosome anomalies on diagnosis and bleeding phenotype in children with hemophilia: A single-institution case series.

Hemophilia is an inherited X-linked bleeding disorder characterized by deficiencies of factors VIII or IX. Concomitant X chromosome disorders can impact bleeding phenotype, complicating timely diagnosis and disease management. Herein, we describe three cases of female and male pediatric patients with hemophilia A or B diagnosed between 6 days and 4 years old in the setting of skewed X chromosome inactivation, Turner syndrome, or Klinefelter syndrome.

The emotional experience of mothers of children with haemophilia: maternal guilt, effective coping strategies and resilience within the haemophilia community.

Introduction: Mothers of children with haemophilia (CWH) experience guilt related to this genetic condition. Several factors contributing to maternal guilt have been identified, but the scope and extent of guilt have not previously been quantified.

Aim: This study provides insight into the experience of mothers of CWH and how they perceive and manage guilt.

Genome-Wide Association Study to Find Modifiers for Tetralogy of Fallot in the 22q11.2 Deletion Syndrome Identifies Variants in the Locus on 5q14.3.

Background: The 22q11.2 deletion syndrome (22q11.2DS; DiGeorge syndrome/velocardiofacial syndrome) occurs in 1 of 4000 live births, and 60% to 70% of affected individuals have congenital heart disease, ranging from mild to severe.

Examining the Overlap between Autism Spectrum Disorder and 22q11.2 Deletion Syndrome.

22q11.2 deletion syndrome (22q11.2DS) is a genomic disorder reported to associate with autism spectrum disorders (ASDs) in 15-50% of cases; however, others suggest that individuals with 22q11.

Rare copy number variants and congenital heart defects in the 22q11.2 deletion syndrome.

The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS; MIM #192430; 188400) is the most common microdeletion syndrome. The phenotypic presentation of 22q11DS is highly variable; approximately 60-75 % of 22q11DS patients have been reported to have a congenital heart defect (CHD), mostly of the conotruncal type, and/or aortic arch defect.

Compound heterozygous mutations in NEK8 in siblings with end-stage renal disease with hepatic and cardiac anomalies.

We studied two brothers who presented in the newborn period with cardiac, renal, and hepatic anomalies that were initially suggestive of ALGS, although no mutations in JAG1 or NOTCH2 were identified. Exome sequencing demonstrated compound heterozygous mutations in the NEK8 gene (Never in mitosis A-related Kinase 8), a ciliary kinase indispensable for cardiac and renal development based on murine studies. The mutations included a c.

Histone Modifier Genes Alter Conotruncal Heart Phenotypes in 22q11.2 Deletion Syndrome.

We performed whole exome sequence (WES) to identify genetic modifiers on 184 individuals with 22q11.2 deletion syndrome (22q11DS), of whom 89 case subjects had severe congenital heart disease (CHD) and 95 control subjects had normal hearts. Three genes including JMJD1C (jumonji domain containing 1C), RREB1 (Ras responsive element binding protein 1), and SEC24C (SEC24 family member C) had rare (MAF < 0.

Whole-Genome Sequencing and Integrative Genomic Analysis Approach on Two 22q11.2 Deletion Syndrome Family Trios for Genotype to Phenotype Correlations.

The 22q11.2 deletion syndrome (22q11DS) affects 1:4,000 live births and presents with highly variable phenotype expressivity. In this study, we developed an analytical approach utilizing whole-genome sequencing (WGS) and integrative analysis to discover genetic modifiers.

Copy-Number Variation of the Glucose Transporter Gene SLC2A3 and Congenital Heart Defects in the 22q11.2 Deletion Syndrome.

The 22q11.2 deletion syndrome (22q11DS; velocardiofacial/DiGeorge syndrome; VCFS/DGS) is the most common microdeletion syndrome and the phenotypic presentation is highly variable. Approximately 65% of individuals with 22q11DS have a congenital heart defect (CHD), mostly of the conotruncal type, and/or an aortic arch defect.

The effect of hypocalcemia in early childhood on autism-related social and communication skills in patients with 22q11 deletion syndrome.

22q11 deletion syndrome (22qDS), also known as DiGeorge syndrome, is a copy number variant disorder that has a diverse clinical presentation including hypocalcaemia, learning disabilities, and psychiatric disorders. Many patients with 22q11DS present with signs that overlap with autism spectrum disorder (ASD) yet the possible physiological mechanisms that link 22q11DS with ASD are unknown. We hypothesized that early childhood hypocalcemia influences the neurobehavioral phenotype of 22q11DS.

Severe aortopathy due to fibulin-4 deficiency: molecular insights, surgical strategy, and a review of the literature.

Unlabelled: Mutations in the EFEMP2 (alias FBLN4) gene, which encodes the extracellular matrix protein fibulin-4, lead to severe aortopathy with aneurysm formation and vascular tortuosity. The disease phenotype, termed autosomal recessive cutis laxa type 1B (ARCL 1B), is rare among heritable connective tissue diseases but becomes more likely when noting family consanguinity and loose, inelastic skin in the patient. Our patient presented with an intercurrent illness exacerbating upper airway obstruction due to compression from a large aortic aneurysm.

Association of IL-12p70 and IL-6:IL-10 ratio with autism-related behaviors in 22q11.2 deletion syndrome: a preliminary report.

22q11.2 deletion syndrome (22q11DS) is a genetic disorder that conveys a significant risk for the development of social behavior disorders, including autism and schizophrenia. Also known as DiGeorge syndrome, 22q11DS is the second most common genetic disorder and is characterized by an elevated risk for immune dysfunction, up to 77% of individuals have an identifiable immune deficiency.

Overt cleft palate phenotype and TBX1 genotype correlations in velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome patients.

Velo-cardio-facial syndrome/DiGeorge syndrome, also known as 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome, with an estimated incidence of 1/2,000-1/4,000 live births. Approximately 9-11% of patients with this disorder have an overt cleft palate (CP), but the genetic factors responsible for CP in the 22q11DS subset are unknown.

Chromosome 22q11.2 deletion syndrome in African-American patients: a diagnostic challenge.

Chromosome 22q11.2 deletion syndrome (22q11DS) is associated with numerous and variable clinical manifestations including conotruncal heart abnormalities, palatal anomalies, hypoparathyroidism, immune deficiency, and cognitive deficits. The clinical suspicion of this syndrome is often heightened by the presence of characteristic facial features.

Genotype and cardiovascular phenotype correlations with TBX1 in 1,022 velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome patients.

Haploinsufficiency of TBX1, encoding a T-box transcription factor, is largely responsible for the physical malformations in velo-cardio-facial /DiGeorge/22q11.2 deletion syndrome (22q11DS) patients. Cardiovascular malformations in these patients are highly variable, raising the question as to whether DNA variations in the TBX1 locus on the remaining allele of 22q11.

Observation and prediction of recurrent human translocations mediated by NAHR between nonhomologous chromosomes.

Four unrelated families with the same unbalanced translocation der(4)t(4;11)(p16.2;p15.4) were analyzed.

Do neonates with genetic abnormalities have an increased morbidity and mortality following cardiac surgery?

Introduction: Genetic abnormalities occur in approximately 20% of children with congenital heart disease. The purpose of this study was to evaluate the effect of genetic abnormalities on short-term outcomes following neonatal cardiac surgery.

Methods: Retrospective review of all neonates (n = 609) undergoing cardiac surgery from January 2003 to December 2006.

Preaxial hallucal polydactyly as a marker for diabetic embryopathy.

Background: Diabetes is the most common endocrinologic complication during pregnancy, and poor control can lead to a variety of congenital anomalies in the fetus. However, it is often difficult to differentiate between diabetes-related anomalies and an underlying genetic syndrome. In the 1990s it was proposed that preaxial hallucal polydactyly, particularly when proximally placed, was a distinguishing feature of diabetic embryopathy.

Sclerocornea associated with the chromosome 22q11.2 deletion syndrome.

Reported ocular findings in the 22q11.2 deletion syndrome (which encompasses the phenotypes of DiGeorge, velocardiofacial, and Takao (conotruncal-anomaly-face) syndromes) have included posterior embryotoxon (prominent, anteriorly displaced Schwalbe's line at the corneal limbus or edge), retinal vascular tortuosity, eyelid hooding, strabismus, and astigmatism. We present seven 22q11.

A review of neurocognitive and behavioral profiles associated with 22q11 deletion syndrome: implications for clinical evaluation and treatment.

22q11 deletion syndrome (22q11DS) is a chromosomal disorder that results in variable multisystem abnormalities, including conotruncal cardiac malformations, aplasia or hypoplasia of the thymus and/or parathyroid glands, immunodeficiency, dysmorphic facial features, and cleft palate and other nasopharyngeal and dental anomalies. Individuals with 22q11DS also exhibit cognitive and behavioral difficulties, including delayed motor and speech-language development, mental retardation, low academic achievement, impaired spatial reasoning, poor attentional and executive functioning, attention-deficit hyperactivity disorder, autism spectrum disorders, mood disorders, and/or schizophrenia spectrum disorders. Interventions should be designed based on the results of periodic developmental and neuropsychological assessments and psychiatric screening.

Rhabdomyomatous hamartomata of the pharyngeal region with bilateral microtia and aural atresia: a new association?

Background: Bilateral microtia with aural atresia is rare. Rhabdomyomatous hamartomata containing salivary tissue, situated bilaterally and symmetrically simulating the palatine (faucial) tonsils, has apparently not been reported. We present the combination of these findings in two unrelated patients.

Deletion of chromosome 22q11.2 and outcome in patients with pulmonary atresia and ventricular septal defect.

Background: The 22q11.2 deletion (del22q) is present in many patients with conotruncal abnormalities including pulmonary atresia with ventricular septal defect (PA/VSD). We sought to determine the impact of the del22q on outcome in subjects with PA/VSD.

A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population.

Objectives: Although several studies describe the 22q11.2 deletion, population-based data are scant. Such data are needed to evaluate properly the impact, distribution, and clinical presentation of the deletion in the population.