Partial trisomy 2p and partial monosomy 2q arising from a paternal intrachromosomal 2q-into-2p between-arm insertion and paracentric inversion: molecular cytogenetic characterization of a four-break rearrangement.

We report on a 26-month-old boy with an interstitial duplication of 2p22.3p22.2 and an interstitial deletion of 2q14.1q21.2. The abnormality was derived from his father having a balanced paracentric inversion and pericentric insertion. The deletion in the child was identified by cytogenetic analysis and characterized in more detail by molecular cytogenetics and array comparative genomic hybridization. The latter revealed a 20-Mb deletion in the long arm and a 5.6-Mb duplication in the short arm of chromosome 2. Fluorescence in situ hybridization in paternal chromosomes characterized an intrachromosomal insertion of 2q14.1q21.2 into 2p23; additionally a paracentric inversion of 2p13p23 was observed. The boy with the unbalanced karyotype suffered from severe psychomotor retardation, thrombophilia due to protein C deficiency, and hypertrophic cardiomyopathy and also had phenotypic abnormalities. Most of these features have previously been described in individuals with interstitial deletion of 2q14.1.

Tetrasomy 9p mosaicism associated with a normal phenotype in two cases.

Tetrasomy 9p is a rare chromosomal syndrome and about 30% of known cases exhibit mosaicism. Approximately 50 of the reported cases with tetrasomy 9p mosaicism show a characteristic facial appearance, growth failure, and developmental delay. However, 3 patients with mosaicism for isochromosome 9p and a normal phenotype have also been reported. We report 2 additional cases of clinically normal young females with tetrasomy 9p mosaicism, one of whom also exhibited X chromosome aneuploidy mosaicism leading to an overall of 6 different cell lines. STR analysis performed on this complex mosaic case indicated that the extra isochromosome was of maternal origin while the X chromosome aneuploidy was of paternal origin, indicating a postzygotic event.

Attention Deficit/Hyperactivity Disorder (ADHD) symptoms and cognitive skills of preschool children.

Attention deficit/hyperactivity disorder (ADHD) constitutes a neurobehavioral disorder which may potentially adversely affect children's wellbeing and academic achievement. The onset of symptoms is present prior to 12 years of age, and often the symptoms are evident in the preschool years. In fact, it has been suggested that screening for ADHD symptoms may be initiated as early as four years of age. Preschool children with ADHD have been shown to present with poor pre-academic skills and might be at increased risk for numerous school-related problems, including functional impairment during elementary school years and persistent poor academic performance thereafter. Although preschool years are characterized by rapid cognitive growth, preschoolers with ADHD may present with poorer cognitive and neuropsychological functioning. Due to the early onset of ADHD symptoms, exploring the cognitive correlates of this condition among preschool children is thought to be of notable importance. The aim of the present study was to evaluate any association between ADHD symptoms and cognitive skills among preschool children. A cross-sectional study was conducted among a nationwide random sample of 4,480 preschool children. ADHD symptoms were assessed though interviews with parents and teachers based on DSM-IV-TR criteria. Cognitive skills were assessed through a standardized school readiness test (A' TEST). Among participants, the occurrence of ADHD symptoms was 4.6% (boys/girls: 3.4/1). The presence of ADHD symptoms among children was inversely associated with non-verbal and verbal cognitive skills; specifically, with abstract thinking (aOR 1.97, 95% CI 1.30-3.00), language (2.36, 1.55-3.59), critical reasoning (2.58, 1.84-3.62), visual perception (2.42, 1.38- 4.24), and visual motor skills (2.61, 1.91-3.55). Children with ADHD symptoms were five times as likely to have compromised organizational skills (4.92, 3.04-7.97). Abstract thinking was the least affected domain particularly among boys, while organizational skills were the most affected domain in both sexes, and possibly more among girls. Concluding, the present study confirms that even during preschool years, children with ADHD symptoms are more likely to present with concomitant cognitive difficulties. Thus, screening for the presence of ADHD, as well as cognitive and affective screenings among preschool aged children may facilitate the early detection and determent of the development of cognitive difficulties, and subsequently the early intervention for fostering skills that are amenable to change, such as organizational skills and planning. As a result, the study findings reveal the necessity for the evaluation of pre-academic skills among preschool children with ADHD symptoms in order to mitigate unfavorable academic functioning.

A female with Coffin-Lowry syndrome and "cataplexy".

Coffin-Lowry syndrome (CLS) is an X-linked semidominant condition, caused by mutations in the gene encoding the ribosomal protein S6 kinase-2 (RSK-2), a growth factor regulating protein kinase, which is mapped to Xp 22.2. The syndrome is mainly seen in males. It is manifested by moderate to severe mental retardation and characteristic facial, hand and skeletal malformations. We present a female patient with fully manifested CLS, confirmed by molecular analysis, who experienced daily drop episodes, diagnosed as "cataplexy". The episodes were precipitated by emotional or auditory stimuli and were significantly reduced, by selective serotonine re-uptake inhibitors.

A patient with partial trisomy 21 and 7q deletion expresses mild Down syndrome phenotype.

BACKGROUND: Down syndrome (DS) is the most common aneuploidy in live-born individuals and it is well recognized with various phenotypic expressions. Although an extra chromosome 21 is the genetic cause for DS, specific phenotypic features may result from the duplication of smaller regions of the chromosome and more studies need to define genotypic and phenotypic correlations. CASE REPORT: We report on a 26 year old male with partial trisomy 21 presenting mild clinical symptoms relative to DS including borderline intellectual disability. In particular, the face and the presence of hypotonia and keratoconus were suggestive for the DS although the condition remained unnoticed until his adult age array comparative genomic hybridization (aCGH) revealed a 10.1 Mb duplication in 21q22.13q22.3 and a small deletion of 2.2 Mb on chromosomal band 7q36 arising from a paternal translocation t(7;21). The 21q duplication encompasses the gene DYRK1. CONCLUSION: Our data support the evidence of specific regions on distal 21q whose duplication results in phenotypes recalling the typical DS face. Although the duplication region contains DYRK1, which has previously been implicated in the causation of DS, our patient has a borderline IQ confirming that their duplication is not sufficient to cause the full DS phenotype.

De novo 15.5-Mb Interstitial Deletion in 5p in a Male Ascertained by Oligospermia.

We describe a case of a 34-year-old male presenting with oligospermia and an otherwise normal phenotype. Investigation with array-based comparative genomic hybridization (aCGH) revealed an interstitial deletion of about 15.5 Mb in chromosome 5p13.3p14.3. We compared the phenotype of our patient with recently reported patients studied by aCGH, who show an overlapping deletion. We also analyzed the gene content of the deleted region in order to propose a possible involvement of specific genes in the clinical phenotype.

Characterization of 23 small supernumerary marker chromosomes detected at pre-natal diagnosis: The value of fluorescence in situ hybridization.

Small supernumerary marker chromosomes (sSMCs) cannot be identified or characterized unambiguously by conventional cytogenetic banding techniques. Until recently, the large variety of marker chromosomes, as well as the limitations in their identification, have presented a diagnostic problem. In order to determine the origin of sSMCs, we used a variety of fluorescence in situ hybridization (FISH) methods, including centromere-specific multicolor FISH, acrocentric specific multicolor FISH, subcentromere-specific multicolor FISH and multicolor FISH with whole chromosome paint probes. Moreover, uniparental disomy testing was in all cases attempted. From a total of 28,000 pre-natal samples from four diagnostic genetics laboratories in Greece, 23 (0.082%) supernumerary marker chromosomes were detected. The mean maternal age was 36.2 years (range 27-43) and the mean gestational age at which amniocentesis was performed was 18.5 weeks (range 16-23). Eighteen markers were de novo and 5 markers were inherited. Molecular cytogenetic methods were applied to determine the chromosomal origin and composition of the sSMC. In total, 17 markers were derived from acrocentric chromosomes (14, 15, 21 and 22) and 6 markers were non-acrocentric, derived from chromosomes 9, 16, 18, 20 and Y. Uniparental disomy was not detected in any of the cases studied. With regard to pregnancy outcome, 13 pregnancies resulted in normal healthy neonates, while 10 pregnancies were terminated due to ultrasound abnormalities. A total of 23 marker chromosomes from 28,000 pre-natal samples (0.082%) were identified. Molecular cytogenetic techniques provided valuable information on the chromosomal origin and composition of all the sSMCs. Especially in cases with normal ultrasound, the FISH results rendered genetic counseling possible in a category of cases previously considered a diagnostic problem. Abnormal outcome was observed in 10 cases (43,5%), 7 of which showed abnormal ultrasound findings. New technologies, such as array-comparative genomic hybridization, should be used in future genotype-phenotype correlation studies, although the high mosaicism rate poses a problem.

Cohen syndrome: two new cases in siblings.

UNLABELLED: Cohen syndrome is a rare genetic disorder consisting of truncal obesity, hypotonia, mental retardation, characteristic facial appearance and ocular anomalies. Other diagnostic clinical features include narrow hands and feet, low growth parameters, neutropenia and chorioretinal dystrophy. We describe the similarities in the clinical and developmental profile of two siblings with Cohen syndrome, providing evidence for autosomal recessive inheritance in this condition. CONCLUSION: The diagnosis of Cohen syndrome should be suspected in mentally retarded children with the above characteristics. Neutropenia and ocular anomalies with high-grade myopia and chorioretinal dystrophy are also considered important findings and can aid in the clinical diagnosis especially at an early age.