Search

Objective: The 22q11.2 deletion (del22q11.2) is one of the most common microdeletions. We performed a collaborative, retrospective analysis in France of prenatal diagnoses and outcomes of fetuses carrying the del22q11.2., Methods: A total of 272 fetuses were included. Data on prenatal diagnosis, ultrasound findings, pathological features, outcomes and inheritance were analyzed., Results: The mean time of prenatal diagnosis was 25.6 ± 6 weeks of gestation. Most of the diagnoses (86.8%) were prompted by abnormal ultrasound findings [heart defects (HDs), in 83.8% of cases]. On fetal autopsy, HDs were again the most common disease feature, but thymus, kidney abnormalities and facial dysmorphism were also described. The deletion was inherited in 27% of cases. Termination of pregnancy (TOP) occurred in 68.9% of cases and did not appear to depend on the inheritance status. However, early diagnosis was associated with a higher TOP rate., Conclusion: This is the largest cohort of prenatal del22q11.2 diagnoses. As in postnatally diagnosed cases, HDs were the most frequently observed abnormalities. However, thymus and kidney abnormalities and polyhydramnios should also be screened for in the prenatal diagnosis of del22q11.2. Only the time of diagnosis appeared to be strongly associated with the pregnancy outcome: the earlier the diagnosis, the higher the TOP rate., (© 2014 John Wiley & Sons, Ltd.)

Background: Since the advent of array-CGH, numerous new microdeletional syndromes have been delineated while others remain to be described. Although 3q29 subtelomeric deletion is a well-described syndrome, there is no report on 3q interstitial deletions., Methods: We report for the first time seven patients with interstitial deletions at the 3q27.3q28 locus gathered through the Decipher database, and suggest this locus as a new microdeletional syndrome., Results: The patients shared a recognisable facial dysmorphism and marfanoid habitus, associated with psychosis and mild to severe intellectual disability (ID). Most of the patients had no delay in gross psychomotor acquisition, but had severe impaired communicative and adaptive skills. Two small regions of overlap were defined. The first one, located on the 3q27.3 locus and common to all patients, was associated with psychotic troubles and mood disorders as well as recognisable facial dysmorphism. This region comprised several candidate genes including SST, considered a candidate for the neuropsychiatric findings because of its implication in interneuronal migration and differentiation processes. A familial case with a smaller deletion allowed us to define a second region of overlap at the 3q27.3q28 locus for marfanoid habitus and severe ID. Indeed, the common morphological findings in the first four patients included skeletal features from the marfanoid spectrum: scoliosis (4/4), long and thin habitus with leanness (average Body Mass Index of 15 (18.5

Most microdeletion syndromes identified before the implementation of array-comparative genomic hybridization (array-CGH) were presumed to be well-defined clinical entities. However, the introduction of whole-genome screening led not only to the description of new syndromes but also to the recognition of a broader spectrum of features for well-known syndromes. Here, we report on 10 patients presenting with mental retardation associated with atypical features not suggestive of a known microdeletion and a normal standard karyotype. Array-CGH analyses revealed five microdeletions in the DiGeorge region, three microdeletions in the Williams-Beuren region and two microdeletions in the Smith-Magenis region. Reevaluation in these patients confirmed that the diagnosis remained difficult on clinical grounds and emphasized that well-known genomic disorders can have a phenotype that is heterogeneous and more variable than originally thought. The widespread use of array-CGH shows that such patients may be more readily achieved on the basis of genotype rather than phenotype., (© 2011 John Wiley & Sons A/S.)

We report the case of a 26-month-old boy with mental retardation, facial dysmorphism, childhood feeding difficulties, short stature, bilateral cryptorchidism, micropenis, and heart defect. Endocrinal evaluation revealed complete growth hormone deficiency (GHD) and gonadotropic deficiency, and pituitary magnetic resonance imaging showed partial pituitary stalk interruption syndrome (PSIS). A de novo 493 kb microdeletion on chromosome 17q21.31 was identified using array comparative genomic hybridization (array-CGH) analysis. This is the first report of PSIS in the phenotypical spectrum of 17q21.31 microdeletion syndrome, although other midline abnormalities have previously been described. Our report suggests that GHD should be investigated in patients with 17q21.31 microdeletion syndrome and short stature, defined by a body height below - 2 standard deviation scores (SDS) for age and sex. This finding also opens new avenues of research on the etiopathogenesis of PSIS, for which the genetic mechanisms remain unknown., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

BACKGROUND Genome-wide screening of large patient cohorts with mental retardation using microarray-based comparative genomic hybridisation (array-CGH) has recently led to identification several novel microdeletion and microduplication syndromes. METHODS Owing to the national array-CGH network funded by the French Ministry of Health, shared information about patients with rare disease helped to define critical intervals and evaluate their gene content, and finally determine the phenotypic consequences of genomic array findings. RESULTS In this study, nine unrelated patients with overlapping de novo interstitial microdeletions involving 4q21 are reported. Several major features are common to all patients, including neonatal muscular hypotonia, severe psychomotor retardation, marked progressive growth restriction, distinctive facial features and absent or severely delayed speech. The boundaries and the sizes of the nine deletions are different, but an overlapping region of 1.37 Mb is defined; this region contains five RefSeq genes: PRKG2, RASGEF1B, HNRNPD, HNRPDL and ENOPH1. DISCUSSION Adding new individuals with similar clinical features and 4q21 deletion allowed us to reduce the critical genomic region encompassing two genes, PRKG2 and RASGEF1B. PRKG2 encodes cGMP-dependent protein kinase type II, which is expressed in brain and in cartilage. Information from genetically modified animal models is pertinent to the clinical phenotype. RASGEF1B is a guanine nucleotide exchange factor for Ras family proteins, and several members have been reported as key regulators of actin and microtubule dynamics during both dendrite and spine structural plasticity. CONCLUSION Clinical and molecular delineation of 4q21 deletion supports a novel microdeletion syndrome and suggests a major contribution of PRKG2 and RASGEF1B haploinsufficiency to the core phenotype.

We report a new case of megalencephaly and polymicrogyria with post-axial polydactyly and hydrocephalus (MPPH syndrome) in an 18-month-old girl. She was the first child of healthy non-consanguineous parents and measurements at birth were +3 standard deviations (S.D.) for weight, +2 S.D. for length and +4 S.D. for OFC. Ultrasound scan at 24 weeks of gestation (WG) showed mild ventriculomagaly with unique umbilical artery and dacryocystocele. Clinical examination at birth revealed macrosomia with macrocephaly, facial dysmorphism, post-axial polydactyly at the right hand and both feet, and axial hypotonia with hypertonic arms and legs. At 18 months of age, weight was +2 S.D., length was +2 S.D. and OFC was +4 S.D. She remained hypertonic, could not sit and had no hand use. Cerebral magnetic resonance imaging showed stable ventriculomegaly and polymicrogyria located on the frontal and perisylvian region with white matter hypersignal on T2-weighted images. There was no associated visceral malformation. Standard and high-resolution cytogenetic examination, telomeric FISH and array-CGH studies were normal. This case represents the sixth observation of MPPH syndrome as described by Mirzaa et al. in 2004. We provide further neurological follow-up since three out of five index patients were aged 6 months or less. We postulate that macrosomia at birth might be a major feature (five/six cases), with advanced bone age in the two/two investigated cases. White matter abnormalities might be an occasional feature of this syndrome (three/six cases), as well as dacryocystocele, if not coincidental (one/six case). The mode of inheritance of this syndrome remains unknown since there was no significant family history in all reported cases. The search for infracytogenetic chromosomal imbalance was unsuccessful.

The phenotype of mosaic variegated aneuploidy (MVA) syndrome is characterized by severe microcephaly, growth deficiency, mental retardation, and mild physical anomalies. The MVA syndrome is associated with mosaicism for several different aneuploidies involving many different chromosomes with or without premature centromere division (PCD). To date 28 cases of MVA syndrome have been reported. We report the first case of MVA syndrome without microcephaly. The clinical features in our patient included craniofacial dysmorphic features, growth retardation, and developmental delay. Cytogenetics analyses and FISH studies showed multiple aneuploidy with trisomy 18, 19, and 8, respectively in blood lymphocyte and fibroblasts without PCD. This case is compared with the other of MVA syndrome previously reported in literature. From this case report, we suggest that microcephaly is not mandatory for the diagnosis of MVA syndrome., ((c) 2005 Wiley-Liss, Inc.)