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Objectives To determine the frequency of genetic and additional structural abnormalities as well as pregnancy outcomes in fetuses with prenatally diagnosed cephalocele. Methods A retrospective analysis of data retrieved from ultrasound examinations and genetic testing in fetuses with cephalocele diagnosed between 2006 and 2018 in a tertiary referral hospital along with a systematic literature search in the PubMed database on fetuses with prenatally diagnosed cephalocele. Results Twenty-one out of 36 fetuses were found to have additional structural anomalies (58.3%). In four fetuses, anomalies were consistent with limb-body wall complex, in five with Meckel-Gruber syndrome, and in one with amniotic band syndrome. Genetic abnormalities were present in 11.1% of fetuses (trisomy 6; microdeletion 22q11.21; microduplication 16p13.11; pathogenic variant in gene CC2D2A). Twenty-eight pregnancies were terminated (77.8%; 28/36); two were miscarried (5.6%; 2/36). All six children from pregnancies that continued were liveborn but only two survived the surgery and developed neurological sequence. Overall survival rate was 25% (2/8) with 0% intact survival. Conclusions Additional structural anomalies are common in fetuses with cephalocele. A significant number of fetuses have genetic abnormalities, and a detailed genetic testing should be performed in all cases. The prognosis is poor with high mortality rate and 0% intact survival.

We present a case of lethal fetal akinesia deformation sequence (FADS) caused by a frameshift variant in trans with a 148 kbp deletion encompassing 3-36 exons of AGRN. Pathogenic variants in AGRN have been described in families with a form of congenital myasthenic syndrome (CMS), manifesting in the early childhood with variable fatigable muscle weakness. To the best of our knowledge, this is the first case of FADS caused by defects in AGRN gene. FADS has been reported to be caused by pathogenic variants in genes previously associated with CMS including these involved in endplate development and maintenance: MuSK, DOK7, and RAPSN. FADS seems to be the most severe form of CMS. None of the reported in the literature CMS cases associated with AGRN had two null variants, like the case presented herein. This indicates a strong genotype-phenotype correlation.

Objective To present five new cases of prenatally diagnosed Pallister–Killian syndrome (PKS) and to propose an approach for a targeted diagnosis. Method We retrospectively analyzed ultrasound findings and cytogenetic results in PKS. We also searched through dysmorphology databases for features occurring in PKS that could potentially be seen in prenatal ultrasound examination. Results On the basis of collected data, frequent and distinctive features in fetuses with PKS were established. The most appropriate material and method of testing were proposed. Rhizomelic limb shortening, diaphragmatic hernia, thickened nuchal fold, increased prenasal thickness, polydactyly and polyhydramnios were frequent and distinctive findings in fetuses with PKS. Amniocentesis was the most frequent prenatal procedure for material collection. Percentage of aneuploid cells was higher in amniotic fluid than in cord blood. Cytomolecular tests were useful as confirmation as well as preliminary tests. Cytogenetic identification of the isochromosome was done in all cases except one. Conclusions In case of ultrasound evaluation of features frequent and distinctive for PKS in second and third trimesters of pregnancy, targeted diagnosis should be considered. Amniotic fluid instead of cord blood collection is preferable. Communication with the laboratory is important because modification of routine procedures enhances a chance for correct diagnosis. © 2017 John Wiley & Sons, Ltd.

Background Microchimerism is defined as a stable presence of low numbers of cells derived from a different individual due to cell transfer between twins or between mother and fetus during pregnancy. Objective Fetal cells in the organism of the mother (FMc) are postulated to play a role in autoimmune diseases. Psoriasis is a disease which has an autoimmune component, but no study on microchimerism in this disease has been reported. Methods The easiest way to detect microchimerism is to look for male cells in blood or other tissues of a woman who previously delivered a son. Here, we looked for the presence of male cells in mononuclear cell subpopulations from peripheral blood and in skin samples of women with psoriasis and of healthy women. Results We detected FMc in similar proportions of patients and controls in CD4+, CD8+ and CD34+ cells, whereas in CD34- cells they were present in higher fraction of controls, and similar but non-significant difference was observed in CD19+ cells. No microchimeric cells were detected in patients' skin samples, both from affected and non-affected skin, or in skin tissue from healthy control individuals. Conclusion Our result does not prove the involvement of microchimerism in the aetiology of psoriasis.

Neurodevelopmental disorders have long been associated with chromosomal abnormalities, including microdeletions and microduplications. Submicroscopic 14q11.2 deletions involving the CHD8 and SUPT16H genes have been reported in patients with developmental delay (DD)/intellectual disability (ID) or autism spectrum disorders (ASDs) and/or macrocephaly. Recently, disruptive CHD8 mutations were described in patients with similar phenotypes further showing pivotal role of CHD8 gene in the pathogenesis of DD/ID or ASDs. We report here the first case of ∼445 kb de novo microduplication, encompassing the minimal critical 14q11.2 deletion region, in 8-year-old boy showing DD, cognitive impairment and facial dysmorphism. Our results suggest that gain of the chromosomal region 14q11.2 is causative for clinical findings present in the patient. © 2016 Wiley Periodicals, Inc.

The identification of chromosomal breakpoints in association with human abnormal phenotypes can enable elucidation of gene function. We report on epiphyseal aseptic necrosis of the lesser head of the second metatarsal bone, known as Freiberg's infraction (FI), in two female carriers of the apparently balanced t(5;7)(p13.3;p22.2) ascertained by a 16-year-old girl with cri-du-chat syndrome and unusual skeletal features in association with an unbalanced translocation der(5) t(5;7)(p13.3;p22.2). Mapping of the chromosome breakpoints using fluorescent in situ hybridization (FISH) narrowed them to the coding sequence of ADAMTS12 on chromosome 5p13.3 and SDK1 on 7p22.2. In addition, several skeletal abnormalities classified as brachydactyly type A1B (BDA1B) were present in the proband and in both carriers of t(5;7)(p13.3;p22.2), suggesting a potential role of ADAMTS12 in the development of the BDA1B observed in this family.

We report on a de novo interstitial deletion of 20q11.21–q11.23 in a 2-year-old girl with a set of dysmorphic features, cleft palate, heart defect, severe feeding problems, failure to thrive, developmental delay, preaxial polydactyly (right thumb), and retinal dysplasia. Interstitial microdeletions of the long arm of chromosome 20 are rare. Exclusively rare are proximal microdeletions involving 20q11–q12 region. Our patient is the fourth described so far and has the smallest deleted region 20q11.21–q11.23 of 5.7 Mb. The defined clinical phenotype of our patient is very similar to previously published cases and confirms the existence of retinal dysplasia and skeletal abnormalities as a part of phenotypic spectrum for deletion 20q11–q12. Description of four similar patients, including two almost identical, suggests a new distinct, phenotypicaly recognizable microdeletion syndrome associated with the loss of 20q11–q12 region. © 2014 Wiley Periodicals, Inc.

Complex chromosome rearrangements (CCRs) are rare structural abnormalities that involve at least two chromosomes and more than two breakpoints and are often associated with developmental delay, mental retardation, and congenital anomalies. We report on a de novo, apparently balanced translocation t(1;5;7)(p32.1;q14.3;p21.3) involving three chromosomes in a 7-year-old boy with severe psychomotor retardation, neonatal muscular hypertonia, congenital heart defect, polysyndactyly of hands and feet, and dysmorphic features resembling Greig cephalopolysyndactyly syndrome. Analysis of the chromosome breakpoints using fluorescence in situ hybridization (FISH) with locus-specific BAC clones and long-range PCR products did not identify chromosome imbalance at any of the interrogated regions. High-resolution comparative genomic hybridization (HR-CGH) and array CGH (aCGH) revealed two additional cryptic de novo deletions, del(1)(p31.1p31.1) and del(7)(p14.1p14.1), respectively, that are not associated with the translocation breakpoints. FISH and polymorphic marker analyses showed that the deletion on derivative chromosome 1 is between 4.2 and 6.1 Mb, and the deletion on derivative chromosome 7 is approximately 5.1 Mb, and that both are paternal in origin. The deletion on chromosome 7p encompasses the GLI3 gene that is causative for the Greig cephalopolysyndactyly, Pallister-Hall and some cases of Acrocallosal syndromes. We discuss the potential mechanisms of formation of the described CCR.

We present four patients, in whom we identified overlapping deletions in 5q14.3 involving MEF2C using a clinical oligonucleotide array comparative genomic hybridization (CGH) chromosomal microarray analysis (CMA). In case 1, CMA revealed an approximately 140 kb deletion encompassing the first three exons of MEF2C in a 3-year-old patient with severe psychomotor retardation, periodic tremor, and an abnormal motor pattern with mirror movement of the upper limbs observed during infancy, hypotonia, abnormal EEG, epilepsy, absence of speech, autistic behavior, bruxism, and mild dysmorphic features. MRI of the brain showed mild thinning of the corpus callosum and delay of white matter myelination in the occipital lobes. In case 2, an approximately 1.8 Mb deletion of TMEM161B and MEF2C was found in a child with severe developmental delay, hypotonia, and seizures. Patient 3 had epilepsy, hypotonia, thinning of the corpus callosum, and developmental delay associated with a de novo approximately 2.4 Mb deletion in 5q14.3 including MEF2C and five other genes. In case 4, a de novo approximately 5.7 Mb deletion of MEF2C and five other genes was found in a child with truncal hypotonia, intractable seizures, profound developmental delay, and shortening of the corpus callosum on brain MRI. These deletions further support that haploinsufficiency of MEF2C is responsible for severe mental retardation, seizures, and hypotonia. Our results, in combination with previous reports, imply that exon-targeted oligo array CGH, which is more efficient in identifying exonic copy number variants, should improve the detection of clinically significant deletions and duplications over arrays with probes spaced evenly throughout the genome.