1/26. child with velocardiofacial syndrome and del (4)(q34.2): another critical region associated with a velocardiofacial syndrome-like phenotype.We report on a child with congenital heart disease (atrial septal defect, ventricular septal defect, pulmonic stenosis), submucosal cleft palate, hypernasal speech, learning difficulties, and right fifth finger anomaly manifestations, consistent with velocardiofacial syndrome (VCFS); however, cytogenetic analysis demonstrated a small terminal deletion of the segment 4q34.2 to 4qter. Fluorescent in situ hybridization did not identify a deletion of the critical region associated with VCFS. In previously reported 4q deletions with a breakpoint distal to 4q34.2, no cardiac defects or cleft of palate were reported. Our patient has a deletion of 4q34.2 to 4qter and has palate and cardiac involvement and minor learning difficulties, which implies that genes involved in heart and palate development lie distal to 4q34.2, and that the critical region for more severe mental retardation on 4q may reside proximal to 4q34.2. These results suggest that a distal 4q deletion can lead to a phenotype similar to VCFS and emphasizes the importance of searching for other karyotype abnormalities when a VCFS-like phenotype is present and a 22q deletion is not identified.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
2/26. Patient with a 22q11.2 deletion with no overlap of the minimal digeorge syndrome critical region (MDGCR).The apparent lack of genotype/phenotype correlation in patients with the DiGeorge anomaly and velocardiofacial syndrome (DGA/VCFS; the "22q11 deletion syndrome") indicates a complex genetic condition. Most cases, whatever the phenotype, have a 1.5-3 Mb chromosomal deletion that includes the minimal DiGeorge critical region (MDGCR). Another potential critical region on 22q11 has been suggested based on two patients with distal deletions outside the MDGCR. We report on a patient with a VCFS phenotype who has a deletion, mapped by short tandem repeat polymorphic loci and fluorescence in situ hybridization analysis, distal to and not overlapping the MDGCR. This patient is deleted for several genes, including the T-box 1 gene (TBX1; a transcription regulator expressed early in embryogenesis) and catechol-O-methyltransferase (COMT; involved in neurotransmitter metabolism). We discuss the role these two genes may play in the clinical phenotype of the patient.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
3/26. Novel assay for Roberts syndrome assigns variable phenotypes to one complementation group.Roberts syndrome (RS) is a rare autosomal recessive disorder characterized by heterogeneous clinical features, the most notable being tetraphocomelia, cleft lip, and cleft palate. cells derived from most RS patients exhibit abnormal cytogenetic and cellular phenotypes that include the premature separation of para- and pericentromeric heterochromatin visible on C-banded metaphase chromosomes, a phenomenon referred to as heterochromatic splaying. Previously, it was shown that these abnormal phenotypes can be complemented following somatic cell hybridization between RS cells and control cells. In the current study, a permanent cell line was established from a new RS patient with a more severe phenotype than represented by previously established cells in culture. With a newly developed assay designed to facilitate rapid evaluation of in vitro complementation, we assigned this new patient to the same genetic complementation group defined by other, less severely affected patients. The results demonstrate that a single complementation group defines RS patients with heterochromatic splaying regardless of clinical severity.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
4/26. 4p- syndrome and 9p tetrasomy mosaicism with cleft lip and palate.Chromosome 4p- syndrome is a multiple malformation syndrome associated with partial deletion of the short arm of chromosome 4 (4p-). It is characterized by dysmorphic features and retarded development. cleft lip and/or palate are the major clinical manifestations. Cases of tetrasomy 9p are extremely rare; the principal clinical manifestations of this condition are characteristic craniofacial abnormalities, generalized hypotonia and severe mental retardation. We present the first case of a female infant with 4p deletion and tetrasomy 9p mosaicism, exhibiting a left-sided cleft lip, alveolus and soft palate. karyotype analysis of lymphocytes cultured from the patient revealed that she was mosaic: 86% of the cells were 46, XX, add (4) (p15.32) and 14% were 47, XX, add (4) (p15.32), idic (9)(q12). The G-banding pattern appeared consistent with either translocation or partial proximal deletion of 4p. In order to make a definitive cytogenetic diagnosis of isodicentric chromosome 9, fluorescence in situ hybridization (FISH) was applied. At 8 months, when the patient weighed 4.3 kg, her cleft lip was repaired. Before and after surgery there were no seizures, and the postoperative course was uneventful.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
5/26. Misclassification risk of patients with bilateral cleft lip and palate and manifestations of median facial dysplasia: A new variant of del(22q11.2) syndrome?The generic term median facial dysplasia (MFD) describes a subgroup of patients with cleft lip and palate exhibiting characteristic craniofacial defects: (1) short prolabium, (2) absence of frenulum labii, (3) hypoplasia of premaxilla, (4) absent upper central and lateral incisors of the cleft side, and (5) deficient septal cartilage and nasal spine. Gross brain malformations are usually absent in MFD. The same craniofacial malformations are also described in patients with holoprosencephaly sequence (HPE-S). We report on two male patients with bilateral cleft lip and palate showing the facial findings of MFD or HPE-S. Additional congenital malformations were anal atresia in one patient and severe cardiac defect in the other. In both, HPE was excluded by brain imaging, although uncommon brain anomalies were detected consisting of multiple white-matter lesions in the one patient and unusual enlargement and tortuosity of intracerebral blood vessels in both patients. In addition to facial anomalies, the patients also had psychiatric problems typically seen in velo-cardio-facial syndrome (VCFS). fluorescence in situ hybridization (FISH) analysis confirmed a 22q11.2 microdeletion in both.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
6/26. cleft palate in a patient with Williams' syndrome.cleft lip or palate has not been reported in the medical literature as a part of Williams' syndrome. We present a patient who had cleft palate among other congenital manifestations. This patient's immediate postnatal period clinically seemed to have a Pierre Robin sequence. With the development of the craniofacial complex, microgenia and micrognathia with glossoptosis gradually became apparent. On further assessment, the patient showed other clinical findings that suggested a syndromic association. This required a complete evaluation to discard other conditions that present with low psychomotor development and distinctive facies, such as Kabuki syndrome or fetal alcohol syndrome. The diagnosis for Williams' syndrome was established based on the clinical features and supported by the fluorescent in situ hybridization test. Williams' syndrome has been described as a rare, congenital disorder characterized by physical and developmental problems. Common features include characteristic "elfin-like" facies, supravalvular aortic stenosis, hypercalcemia, low birth weight, slow weight gain, feeding problems, impulsive and outgoing personality, limited spatial skills and motor control, and intellectual disability. Although individuals with Williams' syndrome may show competence in areas such as language, music, and interpersonal relations, their IQs are usually low and they are considered moderately to mildly retarded.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
7/26. Tissue-limited mosaicism in Pallister-Killian syndrome -- a case in point.We report a case of Pallister-Killian syndrome in a term female infant. Antenatal ultrasound showed left diaphragmatic hernia and polyhydramnios. She was ventilated from birth and the diaphragm defect repaired on day 5. She had dysmorphic features, including median cleft palate, patchy frontotemporal alopecia, hypopigmented skin whorls, and bilateral profound sensorineural hearing loss. Fetal and postnatal karyotypes of peripheral lymphocytes were both normal, 46, XX. Subsequently, a skin fibroblast culture showed mosaic tetrasomy of isochromosome 12p both on G-banding and fluorescence in situ hybridization, consistent with Pallister-Killian syndrome. This case illustrates the importance of using the appropriate sample type for karyotype analysis with implications for prenatal and postnatal diagnosis.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
8/26. Duplication of (2)(q11.1-q13.2) in a boy with mental retardation and cleft lip and palate: another clefting gene locus on proximal 2q?A 4-year-old boy with left cleft lip and cleft palate, multiple minor anomalies and developmental delay revealed an abnormal chromosome 2 with enlarged proximal long arm, de novo, in his karyotype. fluorescence in situ hybridization with a chromosome 2 library and band-specific YACs confined the duplicated segment to 2q11.1-q13.2 and indicated a direct tandem duplication due to unbalanced crossover between chromatids.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
9/26. Terminal tandem duplication of 16p: a case with "pure" partial trisomy (16)(pter-->p13).A new-born infant was found to have multiple congenital anomalies Including bilateral cleft of lip and palate, club-hands and feet, and heart defects. High resolution chromosome analysis showed a de novo tandem duplication of the terminal part of the short arm of chromosome 16, resulting in a dup(16)(pter-->p13). Fluorescent in situ hybridization with a chromosome 16-specific paint confirmed that the extra material belonged to chromosome 16.- - - - - - - - - - ranking = 1keywords = hybridization (Clic here for more details about this article) |
10/26. Velocardiofacial syndrome in an unexplained XX male.We report the unusual finding of velocardiofacial syndrome (VCF) in an unexplained 46,XX male. A microdeletion of 22q11.2 was confirmed by fluorescence in situ hybridization (FISH) analysis. Routine G-banded chromosome analysis revealed an XX sex chromosome constitution. FISH was performed using the SRY probe and failed to detect hybridization. The sex chromosome status of the patient was further investigated by PCR testing to screen for the presence of 24 distinct loci spanning the y chromosome. PCR screening failed to detect any apparent y chromosome material.- - - - - - - - - - ranking = 2keywords = hybridization (Clic here for more details about this article) |
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