The first post-natal clinical description of true mosaic complete tetrasomy 21: A case report.

Tetrasomy 21 is a rare occurrence. Only 14 cases have been reported in the literature, 8 of which are partial tetrasomy cases and 6 which are complete tetrasomy cases. Of the incidences, no proband with true complete tetrasomy 21 has survived the neonatal period. We report complete mosaic tetrasomy 21 in a female infant with the typical Down syndrome phenotype, including Hirschsprung's disease and atrioventricular (AV) canal defect. This is in contrast to cases of partial tetrasomy 21, which often have an atypical trisomy 21 presentation and multiple nonspecific traits, including short stature, microcephaly, and developmental delays. This case demonstrates the difference in clinical presentation between the partial and complete subtype of tetrasomy 21 and provides the first postnatal clinical picture of an infant with true mosaic complete tetrasomy 21.

The first de novo non-mosaic 14q11.2q13.1 tetrasomy of paternal origin.

Tetrasomy 14q11q13 is a very rare chromosome aberration. So far, only five patients with such an imbalance were described. All these patients had a de novo marker chromosome idic(14)(q13) leading to a partial tetrasomy of chromosome 14. We report on the first case of a de novo non-mosaic partial tetrasomy 14q resulted not from a marker chromosome, but from an inverted triplication on paternal chromosome 14, characterized by using FISH and SNP array. Our patient showed some anomalies described in tetrasomy 14q11q13 with striking presence of paternal UPD(14) features (blepharophimosis, small thorax, and joint contractures, developmental delay). This unique patient supports the hypothesis that 14q11q13 may contain imprinted gene(s) that contribute to the paternal UPD(14) features of joint contractures and/or blepharophimosis. This patient demonstrates the utility of parent of origin testing in patients with de novo chromosome 14 aberrations. Overdosage of 14q11.1q13.1 may cause some features related to UPD(14) phenotype.

Pallister-Killian syndrome: a study of 22 British patients.

BACKGROUND: Pallister-Killian syndrome is a rare, sporadic condition caused by mosaic tetrasomy of the short arm of chromosome 12 (12p). The main features are intellectual disability, seizures, dysmorphic features and a variety of congenital malformations. Most available information comes from individual case reports. We report the results of a British study into Pallister-Killian syndrome, which is the first to provide comprehensive data on a population-based sample. METHOD: A detailed phenotypical study was carried out in Great Britain. All individuals with Pallister-Killian syndrome were eligible to participate. Each participant underwent a structured history, developmental assessment and clinical examination. Buccal mucosal samples were analysed by interphase fluorescence in situ hybridization (FISH) and blood samples by array comparative genomic hybridization (CGH). Genotype-phenotype correlations were sought in these tissues and existing skin biopsy reports. RESULTS: Twenty-two patients with Pallister-Killian syndrome, ranging from 4 months to 31 years were recruited and comprehensive data on each obtained. The birth incidence was 5.1 per million live births. Array CGH only suggested the diagnosis in 15.8% but buccal FISH could have made the diagnosis in 75.0%. There was no genotype-phenotype correlation in any of the tissues studied. This study shows that the high birth weights and profound intellectual disability classically described in Pallister-Killian syndrome are not universal. Mild or moderate intellectual disability was present in 27.6% of this cohort and all birth weights were within 2.67SD of the mean. New features which have not previously been recognised as part of Pallister-Killian syndrome include anhydrosis/hypohydrosis and episodic hyperventilation, suggesting involvement of the autonomic system.

De novo 11q13.4q14.3 tetrasomy with uniparental isodisomy for 11q14.3qter.

Interstitial triplications in conjunction with uniparental disomy (UPD) have been rarely reported. Here we report on a patient with de novo triplication at 11q13.4-q14.3 and UPD for 11q14.3-qter. Chromosomal analysis showed a karyotype of 46, XYqh+, der (11), and normal parental karyotypes. A single nucleotide polymorphism (SNP) array detected an 18.7 Mb copy number gain consistent with tetrasomy for 11q13.4-q14.3 (chr11:71,002,347 bp-89,725,167 bp, hg19) and absence of heterozygosity for a 45 Mb stretch on 11q and consistent with uniparental isodisomy at 11q14.3-qter (chr11:89,843,477 bp-134,930,689 bp, hg19) in our patient. FISH analysis using two probes on both sides of the tetrasomic region showed an inverted 11q13.4-q14.3 region between two direct oriented 11q13.4-q14.3 segments (11q13.4-q14.3::11q14.3-q13.4::11q13.4-qter). Previously reported features of duplication overlapping 11q13-q14 showed clinical variability. Our patient presented with some of those frequently described features, such as development delay, facial dysmorphism, and microcephaly but without congenital heart disease. Moreover, our patient had in addition a brain anomaly (absence of cerebellar vermis and partial absence of corpus callosum) which has not been reported. To our knowledge, this is the sixth patient reported an intrachromosomal triplication together with UPD. Interstitial 11q duplication overlapping 11q13-q14 is associated with intellectual disability/development delay, microcephaly, and facial dysmorphism but also other malformations.

Tetrasomy 13q32.2qter due to an apparent inverted duplicated neocentric marker chromosome in an infant with hemangiomas, failure to thrive, laryngomalacia, and tethered cord.

BACKGROUND: Approximately 100 small supernumerary marker chromosomes (sSMCs) with a non-α-satellite neocentromere structure have been reported in the literature. Of the few derived from chromosome 13, five have consisted of inverted duplicated segment 13q32qter. CASE REPORT: We herein describe the sixth case, characterized by genome wide SNP array, conventional cytogenetics and FISH studies. The de novo occurrence of the marker, the poor prognosis and the presence of hemangiomas are consistent with previous cases. CONCLUSION: We hereby expand the clinical spectrum of this rare cytogenetic disorder and suggest a possible mechanism for the pathogenesis of associated congenital vascular malformations.

Tetrasomy 15q26: a distinct syndrome or Shprintzen-Goldberg syndrome phenocopy?

PURPOSE: The aim of this study was to characterize the clinical phenotype of patients with tetrasomy of the distal 15q chromosome in the form of a neocentric marker chromosome and to evaluate whether the phenotype represents a new clinical syndrome or is a phenocopy of Shprintzen-Goldberg syndrome. METHODS: We carried out comprehensive clinical evaluation of four patients who were identified with a supernumerary marker chromosome. The marker chromosome was characterized by G-banding, fluorescence in situ hybridization, single nucleotide polymorphism oligonucleotide microarray analysis, and immunofluorescence with antibodies to centromere protein C. RESULTS: The marker chromosomes were categorized as being neocentric with all showing tetrasomy for regions distal to 15q25 and the common region of overlap being 15q26→qter. CONCLUSION: Tetrasomy of 15q26 likely results in a distinct syndrome as the patients with tetrasomy 15q26 share a strikingly more consistent phenotype than do the patients with Shprintzen-Goldberg syndrome, who show remarkable clinical variation.

Diagnosis and clinical delineation of mosaic tetrasomy 5p.

OBJECTIVE: Our objective was to review the phenotypic and genetic characteristics of tetrasomy 5p from the fetal period until adulthood including prenatal diagnostic evaluations. BACKGROUND: Tetrasomy 5p is a rare chromosomal abnormality. Of the 14 reports, most document mosaic tetrasomy 5p resulting from a supernumerary marker chromosome or isochromosome. There is a wide range of phenotypic manifestations with severity related to more proximal breakpoints and the degree of mosaicism. DESIGN: We conducted a systematic review using Scopus, PubMed Central® and Ovid MEDLINE® from inception through July 1, 2018 for all articles describing tetrasomy 5p. All articles describing the syndrome of tetrasomy 5p were included. RESULTS: Of the 15 included cases, 13 exhibited mosaic tetrasomy and two had complete tetrasomy identified by amniocentesis. The most common features include seizures (8/11 live births, 73%), hypotonia (7/11 live births, 64%), developmental delay (7/9 cases that reached childhood, 78%), abnormal external ears (6/11 live births, 55%), short stature (6/11 live births, 55%), ventriculomegaly (5/11 live births, 45.5%) and congenital heart defect (6/15 cases, 40%). The clinical phenotype ranged in severity from mild with no defining characteristics to severe with seizures, developmental delay, and multiple congenital anomalies, resulting in early death. Of these 15 cases, only 6 were diagnosed prenatally by prenatal genetic testing (40%) with prenatal ultrasound identifying abnormalities in 4/6 (67%). Confined placental mosaicism (CPM) was diagnosed in six additional cases due to discordance between CVS and amniocentesis results. Four of the five live births returned for evaluation and each showed normal development. CONCLUSIONS: Fourteen out of 15 (93%) cases of tetrasomy 5p were associated with an abnormal phenotype. Once a diagnosis is made prenatally, a detailed anatomy ultrasound and fetal echocardiogram must be performed to further characterize any structural abnormalities of the fetus and potentially estimate the clinical severity. Caution should be exercised when prenatal diagnosis of mosaic tetrasomy 5p is found by chorionic villus sampling. CVS alone is insufficient to diagnose tetrasomy 5p and needs to be confirmed with amniocentesis. Our review seeks to inform clinicians on the current literature regarding tetrasomy 5p so that they may better counsel patients when this syndrome is diagnosed.

Anestesia em criança com síndrome de Pallister-Killian: relato de caso / Anesthesia in child with Pallister-Killian syndrome: case report

JUSTIFICATIVA E OBJETIVOS: A síndrome de Pallister-Killian (SPK) é uma doença genética rara causada por uma anomalia, em mosaico, no cromossomo 12. Há pouca informação sobre esta síndrome na literatura anestésica. O objetivo deste relato foi divulgar e discutir as características que podem ser de interesse para a anestesia. RELATO DO CASO: Paciente do sexo masculino, 5 anos de idade, foi submetido a anestesia geral para a realização de ressonância magnética do crânio. Apresentava as características típicas da SPK: dismorfismo facial, alopecia temporal, micrognatismo, macroglossia, retardo mental, convulsões e alterações pigmentares cutâneas. A anestesia foi induzida e mantida com sevoflurano sob máscara facial e cânula orofaríngea, com ventilação assistida manual durante a indução. Não houve intercorrências e o exame foi feito em regime ambulatorial. CONCLUSÕES: A importância da avaliação pré-anestésica é enfatizada, devido às malformações, inclusive cardíacas, associadas a esta síndrome. É recomendada a preparação para possível dificuldade de intubação traqueal ou de manutenção das vias aéreas.