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The increasing number of children conceived following preimplantation genetic diagnosis (PGD) necessitates the evaluation of their motor and cognitive development. The primary study objective was to evaluate the physical, developmental, and neurological outcome of children born after PGD in Greece. In addition, the secondary study objective was to compare the stress levels regarding parental roles between parents of PGD children and those of naturally conceived children. A cross-sectional study design was applied. The study population consisted of 31 children (aged 2 months to 7.5 years) born after PGD analysis and their parents. The developmental evaluation of children included a detailed physical evaluation and cognitive assessment with the Bayley Scales of Infant Development. The parent stress index was applied to evaluate comparative parental stress levels between those parents of PGD children and those of naturally conceived healthy children. High rates of caesarean deliveries, increased incidence of prematurity, multiples and low-birth weight were observed among the 31 PGD children. Overall, 24 of the 31 PGD children had cognitive skills within normal range [general developmental quotient (GDQ): 86–115], while 6 children had lower levels of cognitive skills (GDQ

The 4q deletion syndrome, comprising all microscopically visible deletions (interstitial and terminal) is a well-recognized distinctive malformation entity, with an estimated incidence of 1:10,000. Here we present the clinical and molecular findings in a 3-year-old male with a de novo distal deletion of 4q33 [46,XY,del(4) (q33)]. Clinical findings of the patient include: hypertelorism, broad nasal bridge, short nose with anteverted nares, long philtrum, thin upper lip, micro-retrognathia, low-set and protruding ears, pre-auricular tag unilaterally, low posterior hairline, clinodactyly of the 5th fingers, tapering fingers, hypospadias, and severe psychomotor retardation. Soon after birth he developed severe hypotonia and feeding difficulties. Echocardiography at 15 months documented aortic supravalvular membrane resulting in mild aortic stenosis and dysplasia of the pulmonary valve. Genome-wide screening using 1 Mb resolution array-CGH and subsequent FISH analyses defined a 18.9-22.9 Mb deletion located at the beginning of 4q33 and extending to the telomere. The description of additional cases with similar distal deletions of 4q33 will allow a more precise prognosis and is therefore of great value for genetic counsellors, while detailed molecular characterization in any well clinically characterized patient is expected to track down individual candidate genes for the specific features of the syndrome.

Saethre-Chotzen syndrome represents one of the most common types of craniosynostosis inherited as an autosomal dominant disorder while sporadic cases have also been reported. It is characterized by high penetrance and variable expressivity, leading to difficulties in clinical diagnosis. Some patients, who exhibit most of the diagnostic criteria of Saethre-Chotzen syndrome, have structural abnormalities of chromosome 7. The case of a 4 year old boy with notable dysmorphic features compatible with Saethre-Chotzen syndrome and severe developmental delay is described. Conventional and molecular cytogenetic analysis of peripheral blood samples from the patient and his parents revealed partial monosomy of chromosomal region 7p15 --pter de novo. The TWIST gene, located on chromosome 7p21.1, is thought to be a negative transcriptional regulator involved in osteoblast differentiation and maturation and it is thought that haploinsufficiency of the gene can cause the disorder. The diagnosis of Saethre-Chotzen syndrome and the identification of the chromosomal abnormality in the patient facilitated genetic counseling of the family.

Goldenhar (GS) syndrome is a well-recognised developmental disorder involving first and second branchial arches and characterized by considerable phenotypic variability. The present study presents clinical data on the morphologic features, hearing, ophthalmologic, orthopaedic, neurological, cardiovascular, genitourinary and gastrointestinal evaluation of 17 Greek patients (one pair of monozygotic twins) aged 20 days to 23 years with the clinical diagnosis of GS and with a normal karyotype. The most consistent findings were auricular defects (94%), followed by facial (76%) and ocular anomalies (65%), 70% unilateral, mainly right-sided. In the majority of our patients (90%) mandibular hypoplasia was ipsilateral to the dysplastic ear or the most severely affected ear in bilateral cases. Hearing loss, mainly conductive, was noted in 76% of our patients. Skeletal defects were evident in 23%, while cardiovascular, genitourinary and gastrointestinal in 18%, 23% and 12% respectively. The most frequent neurological manifestation was facial nerve paralysis (12%), while the incidence of mental retardation was higher (23%) than reported in the literature, presumably attributed to the severe hearing and vision loss. In a pair of monozygotic twins of our study discordance of clinical findings was noted. Precise evaluation of GS patients and multidisciplinary care management is necessary to avoid possible complications of many systems and to offer appropriate genetic counselling to the family.

We report on a 13-year-old girl with normal karyotype and a de novo cryptic terminal deletion of chromosome 2q, detected by subtelomeric FISH analysis. Further investigation with array-CGH analysis using the 1Mb resolution Spectral Chip 2600 (Spectral Genomics) confirmed the deletion and also showed a deletion of four additional clones. No other abnormalities were detected by array-CGH. FISH studies using 8 BAC-probes were performed for fine mapping of the deletion and confirmed the array results. FISH analysis showed that the deletion breakpoint lies between clones RP11-84G18 and RP11-83N2 (physical distance between clones 0.36Mb) and extends to the telomere. The size of the deletion was estimated to be about 6.4-6.7Mb. Clinical findings include: developmental delay, severe behavioural disturbances, growth-pubertal retardation, congenital conductive mild hearing loss, growth hormone deficiency, compensate hypothyroidism, dysmorphic facial features, excessive joint hypermobility, brachymetaphalangy, abnormal dermatoglyphics and a history of neonatal laryngomalacia, hypotonia and umbilical hernia. The phenotype of our patient is in keeping with those of the literature, with the exception of cardiovascular, urogenital, neurological anomalies and eczema, which were not observed. The report of the clinical and molecular presentation of similar cases will allow accurate phenotype-genotype correlation and proper genetic counseling of the family.

Accurate detection of the abnormal clone in children with persistent cytopenia (PC) may confirm the diagnosis of myelodysplastic syndrome (MDS) and determine prognosis and evolution of the disease. Bone marrow (BM) samples were obtained from 65 children, 11 of which were finally diagnosed as primary or secondary MDS. Ten to 20 G-banded metaphases were analyzed and FISH was performed using a-satellite probes for chromosomes 7 and 8. Conventional cytogenetic analysis (CCA) was successful in 40/65 samples, revealing clonal aberrations in 3 patients with MDS. FISH was successful in all cases, detecting monosomy 7 and trisomy 8 abnormal clones in 5 patients. Abnormalities were identified in 3/6 children with primary MDS and 3/5 with secondary MDS. None of the patients with PC of etiology other than MDS had a clonal abnormality in the BM. The results confirm the high incidence of chromosome abnormalities in childhood MDS and the sensitivity of FISH in detecting minor abnormal clones.