Increased prevalence of unprovoked seizures in patients with a 22q11.2 deletion.

Many neurologic abnormalities have been identified in patients with a deletion of chromosome region 22q11.2, including recurrent, apparently unprovoked seizures. We reviewed the database of patients with a 22q11.

Autosomal dominant inheritance of infantile myofibromatosis.

We present three families with infantile myofibromatosis (IM; OMIM no. 228550) inherited in an autosomal dominant (AD) manner. These three pedigrees prompted re-assessment of pedigrees available within the genetic, oncologic, surgical, and pathologic literature, which suggest autosomal recessive (AR) inheritance.

Long-term follow-up of three individuals with Kabuki syndrome.

Long-term follow-up of three individuals with Kabuki syndrome indicates their phenotype becomes less striking as adults. It is characterized by short stature, obesity, and relatively large head. Long palpebral fissures persist, as does mild to moderate mental retardation.

Independent de novo 22q11.2 deletions in first cousins with DiGeorge/velocardiofacial syndrome.

Deletions of chromosome 22q11.2 are found in the vast majority of patients with DiGeorge/velocardiofacial syndrome (DGS/VCFS). This most frequent microdeletion syndrome is estimated to occur in 1 in 4,000 live births.

Apolipoprotein E genotype and neurodevelopmental sequelae of infant cardiac surgery.

Background: There has been increasing recognition of adverse neurodevelopmental sequelae in some children after repair of congenital heart defects. Even among children with the same cardiac defect, significant interindividual variation exists in developmental outcome. Polymorphisms of apolipoprotein E have been identified as a risk factor for worse neurologic recovery after central nervous system injury.

Aberrant interchromosomal exchanges are the predominant cause of the 22q11.2 deletion.

Chromosome 22q11.2 deletions are found in almost 90% of patients with DiGeorge/velocardiofacial syndrome (DGS/VCFS). Large, chromosome-specific low copy repeats (LCRs), flanking and within the deletion interval, are presumed to lead to misalignment and aberrant recombination in meiosis resulting in this frequent microdeletion syndrome.

Coloboma and other ophthalmologic anomalies in Kabuki syndrome: distinction from charge association.

Kabuki (Niikawa-Kuroki) syndrome is associated with growth retardation, developmental delay, congenital heart disease, cleft palate, and characteristic facial features. Although the external appearance of the eyes has been well-described, the type and frequency of structural and functional eye anomalies has not been emphasized. We report three children with Kabuki syndrome who also had a retinal coloboma.

Craniosynostosis with tracheal sleeve: a patient with Pfeiffer syndrome, tracheal sleeve and additional malformations in whom an FGFR2 mutation was found.

We discuss a patient with Pfeiffer syndrome who had a tracheal sleeve and an FGFR2 mutation. In the light of our findings, and previous reports of patients with craniosynostosis that also reported similar mutations, we suggest that genomic screening for FGFR2 may be useful in cases with negative FGFR2 mutation testing.

Toriello-Carey syndrome: delineation and review.

Toriello and Carey [1988: Am J Med Genet 31:17-23] first described a syndrome with component manifestations of corpus callosum agenesis, unusual facial appearance, Robin sequence, and other anomalies. This was termed the Toriello-Carey syndrome by Lacombe et al. [1992: Am J Med Genet 42:374-376].

T-cell homeostasis in humans with thymic hypoplasia due to chromosome 22q11.2 deletion syndrome.

Patients with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome) typically exhibit thymic hypoplasia, conotruncal cardiac defects, and hypoparathyroidism. The immunodeficiency that results from the thymic hypoplasia has been extensively described and consists primarily of T-cell lymphopenia.

Safety of live viral vaccines in patients with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome).

The package inserts of live viral vaccines include immunodeficiency as a contraindication. Nevertheless, patients with mild forms of immunodeficiency may benefit from vaccination. No published guidelines exist for the administration of these vaccines specifically to patients with chromosome 22q11.

Thrombocytopenia in patients with chromosome 22q11.2 deletion syndrome.

Thrombocytopenia is a common finding in patients with chromosome 22q11.2 deletion syndrome. Patients with chromosome 22q11.

Surgical airway management in Pierre Robin sequence: is there a role for tongue-lip adhesion?

Objective: The purpose of this study was to examine the efficacy of tongue-lip adhesion (TLA) in the management of clinically significant airway obstruction associated with Pierre Robin sequence.

Design: The records of all children admitted to The Children's Hospital of Philadelphia with a diagnosis of Pierre Robin sequence were reviewed. Charts were reviewed for birth data, diagnosis, preoperative airway management methods, and surgical intervention.

Otolaryngologic manifestations of the 22q11.2 deletion syndrome.

Background: The 22q11.2 chromosome deletion syndrome occurs at a frequency of 1 in 4000 live births. Fluorescent in situ hybridization is a reliable means of testing for this genetic abnormality.

Genitourinary malformations in chromosome 22q11.2 deletion.

Purpose: We reviewed our experience with genitourinary malformations associated with chromosome 22q11.2 deletion.

Materials And Methods: We retrospectively reviewed patient intake charts at the 22q clinic at our institution.

Chromosomal and cardiovascular anomalies associated with congenital laryngeal web.

Objective: The purpose of this study was to estimate the frequency of chromosomal and cardiovascular anomalies associated with a congenital laryngeal web.

Methods: We reviewed our experience with 25 patients who underwent intervention for a symptomatic congenital laryngeal web between 1988 and 2000, in order to investigate the frequency of associated chromosomal and cardiovascular anomalies. Twelve patients underwent cytogenetic evaluation, including seven that were tested for a chromosome 22q11 deletion by fluorescence in situ hybridization.

Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes.

Interferon regulatory factor 6 (IRF6) belongs to a family of nine transcription factors that share a highly conserved helix-turn-helix DNA-binding domain and a less conserved protein-binding domain. Most IRFs regulate the expression of interferon-alpha and -beta after viral infection, but the function of IRF6 is unknown. The gene encoding IRF6 is located in the critical region for the Van der Woude syndrome (VWS; OMIM 119300) locus at chromosome 1q32-q41 (refs 2,3).

CD4(+) CD25(+) T-cell production in healthy humans and in patients with thymic hypoplasia.

Regulatory T cells are found primarily in the CD4(+) CD25(+) fraction of T cells and play an important role in the prevention of autoimmunity. We examined CD4(+) CD25(+) T cells in 33 healthy children and adults and compared them to a population with an inherited form of thymic hypoplasia and a predisposition to autoimmune disease. Absolute numbers of CD4(+) CD25(+) T cells were markedly higher in healthy infants than in infants with chromosome 22q11.

Five additional Costello syndrome patients with rhabdomyosarcoma: proposal for a tumor screening protocol.

We report five new cases of rhabdomyosarcoma (RMS) in Costello syndrome. These cases, combined with those previously reported, increase the number of solid tumors to 17 (10 RMSs, 3 neuroblastomas, 2 bladder carcinomas, 1 vestibular schwannoma, 1 epithelioma), in at least 100 known Costello syndrome patients. Despite possible ascertainment bias, and the incomplete identification of all Costello syndrome patients, the tumor frequency could be as high as 17%.

Genomic screening of fibroblast growth-factor receptor 2 reveals a wide spectrum of mutations in patients with syndromic craniosynostosis.

It has been known for several years that heterozygous mutations of three members of the fibroblast growth-factor-receptor family of signal-transduction molecules-namely, FGFR1, FGFR2, and FGFR3-contribute significantly to disorders of bone patterning and growth. FGFR3 mutations, which predominantly cause short-limbed bone dysplasia, occur in all three major regions (i.e.