High cognitive functioning and behavioral phenotype in Pallister-Killian syndrome.

Pallister-Killian syndrome (PKS) is a rare syndrome of multiple congenital anomalies attributable to the presence of a mosaic supernumerary isochromosome 12p. The syndrome presents with a recognizable pattern of findings including: pigmentary skin changes, characteristic facial features (sparse anterior scalp hair, flattened midface, macrostomia, and coarsening of the facial features), and developmental delay. The developmental phenotype of PKS is quite variable, but most are considered to fall into the profound range of developmental retardation. We report on an individual with classical features of PKS with development significantly better than that reported in the literature. Developmental and behavioral testing in this individual alters the range of developmental expectation in PKS, and highlights the need for consideration of chromosomal analysis in individuals with normal or near-normal intelligence if other physical phenotypic features of PKS are present.

A non-sex chromosome marker in a patient with an atypical Ullrich-Turner phenotype and mosaicism of 46,X,mar/46,XX.

The absence of a sex chromosome in conjunction with the presence of a marker chromosome generally implicates a sex chromosome origin for such marker chromosomes. These types of findings are frequently associated with Ullrich-Turner syndrome. We report a patient that presented with an atypical Ullrich-Turner phenotype and a cytogenetic mosaicism of 46,X,mar/46,XX. The marker chromosome was derived from chromosome 20, not from the X or Y chromosome. The patient's clinical features are described and discussed relative to the cytogenetic findings. This case further demonstrates the necessity of marker chromosome identification for accurate phenotype-karyotype correlation.

Prevalence of 22q11 region deletions in patients with velopharyngeal insufficiency.

Velo-cardio-facial syndrome, DiGeorge syndrome, conotruncal anomaly face syndrome, tetralogy of Fallot, and pulmonary atresia with ventricular septal defect are all associated with hemizygosity of 22q11. While the prevalence of the deletions in these phenotypes has been studied, the frequency of deletions in patients presenting with velopharyngeal insufficiency (VPI) is unknown. We performed fluorescence in situ hybridization for locus D22S75 within the 22q11 region on 23 patients with VPI (age range 5-42 years) followed in the Craniofacial Clinic at the University of Florida. The VPI occurred either as a condition of unknown cause (n=16) or as a condition remaining following primary cleft palate surgery (n=7). Six of sixteen patients with VPI of unknown cause and one of seven with VPI following surgery had a deletion in the region. This study documents a high frequency of 22q11 deletions in those presenting with VPI unrelated to overt cleft palate surgery and suggests that deletion testing should be considered in patients with VPI.

Fluorescence in situ hybridization assessment of the telomeric regions of jumping translocations in a case of aggressive B-cell non-Hodgkin lymphoma.

We report a jumping translocation involving a donor chromosome 1 long arm in a case of aggressive B-cell non-Hodgkin lymphoma (NHL). Conventional cytogenetic banding studies demonstrated a breakpoint distal to the heterochromatic region of the donor 1q chromosome. Characterization by fluorescence in situ hybridization (FISH) of the jumping translocation demonstrated an apparent telomeric sequence loss of the recipient chromosomes. Additional cytogenetic aberrations, including the t(18;22) translocation associated with non-Hodgkin lymphoma, were also observed in this case. Cytogenetically similar cases of jumping translocations reported in the literature have implicated a preferential involvement of the donor chromosomes' heterochromatic regions and the telomeric regions of the recipient chromosomes. Jumping translocations are still considered rare and their appearance is associated with a poor prognosis. The presence of these specific findings for this case are discussed and compared with those previously reported in other hematologic disorders.

Juvenile rheumatoid arthritis in velo-cardio-facial syndrome: coincidence or unusual complication?

We report on two patients with velo-cardio-facial syndrome (VCFS) and juvenile rheumatoid arthritis (JRA). The first, a 9-year-old girl, presented with microcephaly, characteristic face, congenital heart disease, and velopharyngeal insufficiency. Fluorescence in situ hybridization (FISH) study showed deletion of D22S75 (N25), confirming the diagnosis of VCFS. At age 7, she developed joint pain, and polyarticular JRA was diagnosed. Awareness of this case led to the subsequent diagnosis of VCFS (also confirmed by FISH) in another, unrelated 12-year-old girl with characteristic face, hypernasal speech, and obesity. JRA was first diagnosed in this case at age 5 years, and she subsequently developed severe polyarticular disease. Neither patient had clinical or laboratory evidence of immunodeficiency. This observation represents the first report of the association of JRA with VCFS and raises the question of whether this is a coincidental association or a rare complication of this condition.

Preaxial acrofacial dysostosis (Nager syndrome) associated with an inherited and apparently balanced X;9 translocation: prenatal and postnatal late replication studies.

We report on an infant with preaxial acrofacial dysostosis (Nager syndrome) who was diagnosed prenatally as having an apparently balanced X/autosome translocation [46,X,t(X;9)(p22.1;q32)mat] inherited from a previously diagnosed mosaic translocation carrier mother [46,XX/46,X,t(X;9)(p22.1;q32)]. Replication studies on amniocytes showed the normal X chromosome to be late replicating while the same studies repeated on the infant's lymphocytes showed the translocated X chromosome to be late replicating in most cells. Late replication studies of the mother's lymphocytes demonstrated that the normal X chromosome was late replicating in most cells. The presence of Nager syndrome in this infant may be the result of critical breakpoints and/or position effects on chromosome 9, inducing expression of a gene responsible for the syndrome.

Cytogenetic and molecular analysis in Angelman syndrome.

We report on cytogenetic and molecular analyses of 29 Angelman syndrome (AS) individuals ascertained in 1990 through the first National Angelman Syndrome Conference. High resolution GTG- and GBG-banded chromosomes were studied. Standard molecular analysis with six 15q11q13 DNA sequences was used to analyze copy number and parental origin of 15q11q13. Concordance between molecular and cytogenetic data was excellent. The combined data showed that 23 of the 27 probands (85%) on whom we had definitive results have deletions of the chromosome 15q11q13 region. Two classes of deletion were detected molecularly: most patients were deleted for the 5 more proximal probes, but in 2 cases the deletion extended distally to include in sixth probe. In the 13 cases where the parental origin of the deleted chromosome 15 could be established, it was maternal. There were no cases of uniparental disomy. Cytological observations of the relative sizes of the heterochromatic regions of the short arm of chromosome 15 suggested that chromosomes with large heterochromatic blocks may be more prone to de novo deletion.