A novel imprinted locus on bovine chromosome 18 homologous with human chromosome 16q24.1.

Genomic imprinting is an epigenetic regulation mechanism in mammals resulting in the parentally dependent monoallelic expression of genes. Imprinting disorders in humans are associated with several congenital syndromes and cancers and remain the focus of many medical studies. Cattle is a better model organism for investigating human embryo development than mice. Imprinted genes usually cluster on chromosomes and are regulated by different methylation regions (DMRs) located in imprinting control regions that control gene expression in cis. There is an imprinted locus on human chromosome 16q24.1 associated with congenital lethal developmental lung disease in newborns. However, genomic imprinting on bovine chromosome 18, which is homologous with human chromosome 16 has not been systematically studied. The aim of this study was to analyze the allelic expressions of eight genes (CDH13, ATP2C2, TLDC1, COTL1, CRISPLD2, ZDHHC7, KIAA0513, and GSE1) on bovine chromosome 18 and to search the DMRs associated gene allelic expression. Three transcript variants of the ZDHHC7 gene (X1, X2, and X5) showed maternal imprinting in bovine placentas. In addition, the monoallelic expression of X2 and X5 was tissue-specific. Five transcripts of the KIAA0513 gene showed tissue- and isoform-specific monoallelic expression. The CDH13, ATP2C2, and TLDC1 genes exhibited tissue-specific imprinting, however, COTL1, CRISLPLD2, and GSE1 escaped imprinting. Four DMRs, established after fertilization, were found in this region. Two DMRs were located between the ZDHHC7 and KIAA0513 genes, and two were in exon 1 of the CDH13 and ATP2C2 genes, respectively. The results from this study support future studies on the molecular mechanism to regulate the imprinting of candidate genes on bovine chromosome 18.

Structural variants in the Epb41l4a locus: TAD disruption and Nrep gene misregulation as hypothetical drivers of neurodevelopmental outcomes.

Structural variations are a pervasive feature of human genomes, and there is growing recognition of their role in disease development through their impact on spatial chromatin architecture. This understanding has led us to investigate the clinical significance of CNVs in noncoding regions that influence TAD structures. In this study, we focused on the Epb41l4a locus, which contains a highly conserved TAD boundary present in both human chromosome 5 and mouse chromosome 18, and its association with neurodevelopmental phenotypes. Analysis of human data from the DECIPHER database indicates that CNVs within this locus, including both deletions and duplications, are often observed alongside neurological abnormalities, such as dyslexia and intellectual disability, although there is not enough evidence of a direct correlation or causative relationship. To investigate these possible associations, we generated mouse models with deletion and inversion mutations at this locus and carried out RNA-seq analysis to elucidate gene expression changes. We found that modifications in the Epb41l4a TAD boundary led to dysregulation of the Nrep gene, which plays a crucial role in nervous system development. These findings underscore the potential pathogenicity of these CNVs and highlight the crucial role of spatial genome architecture in gene expression regulation.

[Genetic analysis of a case with mosaicism complex structural aberration of chromosome 18].

OBJECTIVE: To determine the karyotype of a patient with mosaicism complex structural aberration of chromosome 18. METHODS: A male patient with a 2-year history of infertility presented at the Center of Reproductive Medicine of the Third Hospital of Peking University in October 2019 was selected as the study subject. Clinical data of the patient was collected. Peripheral blood sample was taken for chromosomal karyotyping, copy number variation (CNV) analysis and fluorescence in situ hybridization (FISH) assay. Semen sample was taken for single sperm CNV analysis. RESULTS: The patient was found to have a karyotype of mos 47,XY,del(18)(q21q23),+r(18)(q21q23)[84]/46,XY,del(18)(q21q23)[9]/48,XY,del(18)(q21q23),+r(18)(q21q23)×2[6]/47,XY,del(18)(q21q23),+r(18)(q21q23×2)[1].ish 47,XY,del(18)(q21q23),+r(18)(q21q23)[84]/46,XY,del(18)(q21q23)[9]/48,XY,del(18)(q21q23),+r(18)(q21q23)×2[6]/47,XY,del(18)(q21q23),+r(18)(q21q23×2)[1]del(18)(q21q23)(D18Z1+,18p+,18q+,WCP18+),r(18)(q21q23)(WCP18+),r(18)(q21q23×2)(WCP18+). No pathogenic CNV was identified. Sequencing of 20 single sperms showed that 1 sperm was normal, 1 had yielded no result, 9 had harbored del(18q), 7 had harbored dup(18q)×2, and 2 had harbored dup(18q)×3. The dup/del fragments had both spanned approximately 33 Mb. CONCLUSION: It is rare for carriers of complex structural and numerical abnormalities of chromosome 18 to have a normal phenotype. Based on the accurate cytogenetic and molecular analyses and the single sperm CNV analysis, the influence of the aberrant karyotype on the gametogenesis may be evaluated.

Terminal microdeletion of chromosome 18 in a Malaysian boy characterized with few features of typical 18q- deletion syndrome: a case report.

BACKGROUND: The 18q- deletion syndrome is a rare congenital chromosomal disorder caused by a partial deletion of the long arm of chromosome 18. The diagnosis of a patient with this syndrome relies on the family medical history, physical examination, developmental assessment, and cytogenetic findings. However, the phenotype of patients with 18q- deletion syndrome can be highly variable, ranging from almost normal to severe malformations and intellectual disability, and normal cytogenetic findings are common, thus complicating the diagnosis. Interestingly, only few characteristic features of typical 18q- deletion syndrome were found in the patient, despite sharing the same critical region. To our knowledge, this is the first report of a Malaysian individual with 18q- terminal microdeletion diagnosed with microarray-based technology. CASE PRESENTATION: Here we report a 16-year-old Malaysian Chinese boy, a product of a non-consanguineous marriage, who presented with intellectual disability, facial dysmorphism, high arched palate, congenital talipes equinovarus (clubfoot), congenital scoliosis, congenital heart defect, and behavioral problems. A routine chromosome analysis on 20 metaphase cells showed a normal 46, XY G-banded karyotype. Array-based comparative genomic hybridization was performed using a commercially available 244 K 60-mer oligonucleotide microarray slide according to the manufacturer's protocol. This platform allows genome-wide survey and molecular profiling of genomic aberrations with an average resolution of about 10 kB. In addition, multiplex ligation-dependent probe amplification analysis was carried out using SALSA MLPA kit P320 Telomere-13 to confirm the array-based comparative genomic hybridization finding. Array-based comparative genomic hybridization analysis revealed a 7.3 MB terminal deletion involving chromosome band 18q22.3-qter. This finding was confirmed by multiplex ligation-dependent probe amplification, where a deletion of ten probes mapping to the 18q22.3-q23 region was detected, and further multiplex ligation-dependent probe amplification analysis on his parents showed the deletion to be de novo. CONCLUSION: The findings from this study expand the phenotypic spectrum of the 18q- deletion syndrome by presenting a variation of typical 18q- deletion syndrome features to the literature. In addition, this case report demonstrated the ability of the molecular karyotyping method, such as array-based comparative genomic hybridization, to assist in the diagnosis of cases with a highly variable phenotype and variable aberrations, such as 18q- deletion syndrome.

The molecular mechanisms of recombinant chromosome 18 with parental pericentric inversions and a review of the literature.

Chromosomal rearrangements mostly result from non-allelic homologous recombination mediated by low-copy repeats (LCRs) or segmental duplications (SDs). Recent studies on recombinant chromosome 18 (rec (18)) have focused on diagnoses and clinical phenotypes. We diagnosed two cases of prenatal rec (18) and identified precise breakpoint intervals using karyotype and chromosomal microarray analyses. We analyzed the distribution characteristics of breakpoint repetitive elements to infer rearrangement mechanisms and reviewed relevant literature to identify genetic trends. Among the 12 families with 25 pregnancies analyzed, 68% rec (18), 24% spontaneous abortions, and 8% normal births were reported. In the 17 rec (18) cases, 65% presented maternal origin and 35% were paternal. Short-arm breakpoints at p11.31 were reported in 10 cases, whereas the long-arm breakpoints were located at q21.3 (6 cases) and q12 (4 cases). Breakpoints of pericentric inversions on chromosome 18 are concentrated in p11.31, q21.3, and q12 regions. Rearrangements at 18p11.31 are non-recurrent events. ALUs, LINE1s, and MIRs were enriched at the breakpoint regions (1.85 to 3.42-fold enrichment over the entire chromosome 18), while SDs and LCRs were absent. ALU subfamilies had sequence identities of 85.94% and 83.01% between two pair breakpoints. Small repetitive elements may mediate recombination-coupled DNA repair processes, facilitating rearrangements on chromosome 18. Maternal inversion carriers are more prone to abnormal recombination in prenatal families with rec (18). Recombinant chromosomes may present preferential segregation during gamete formation.

Chromosome 18 Loss of Heterozygosity in Small Intestinal Neuroendocrine Tumours: Multi-Omic and Tumour Composition Analyses.

INTRODUCTION: Small intestinal neuroendocrine tumours (siNETs) are rare neoplasms which present with low mutational burden and can be subtyped based on copy number variation (CNV). Currently, siNETs can be molecularly classified as having chromosome 18 loss of heterozygosity (18LOH), multiple CNVs (MultiCNV), or no CNVs. 18LOH tumours have better progression-free survival when compared to MultiCNV and NoCNV tumours, however, the mechanism underlying this is unknown, and clinical practice does not currently consider CNV status. METHODS: Here, we use genome-wide tumour DNA methylation (n = 54) and gene expression (n = 20 matched to DNA methylation) to better understand how gene regulation varies by 18LOH status. We then use multiple cell deconvolution methods to analyse how cell composition varies between 18LOH status and determine potential associations with progression-free survival. RESULTS: We identified 27,464 differentially methylated CpG sites and 12 differentially expressed genes between 18LOH and non-18LOH (MultiCNV + NoCNV) siNETs. Although few differentially expressed genes were identified, these genes were highly enriched with the differentially methylated CpG sites compared to the rest of the genome. We identified differences in tumour microenvironment between 18LOH and non-18LOH tumours, including CD14+ infiltration in a subset of non-18LOH tumours which had the poorest clinical outcomes. CONCLUSIONS: We identify a small number of genes which appear to be linked to the 18LOH status of siNETs, and find evidence of potential epigenetic dysregulation of these genes. We also find a potential prognostic marker for worse progression-free outcomes in the form of higher CD14 infiltration in non-18LOH siNETs.

[Genetic analysis of a Chinese pedigree with 18q21.2-q22.3 duplication and deletion in two offspring respectively resulting from a maternal intrachromosomal insertion].

OBJECTIVE: To provide prenatal diagnosis, pedigree analysis and genetic counseling for a pregnant woman who had given birth to a child featuring global developmental delay. METHODS: A pregnant woman who underwent prenatal diagnosis at the Affiliated Hospital of Southwest Medical University in August 2021 was selected as the study subject. Peripheral blood samples were collected from the woman, her husband and child, in addition with amniotic fluid sample during mid-pregnancy. Genetic variants were detected by G-banded karyotyping analysis and copy number variation sequencing (CNV-seq). Pathogenicity of the variant was predicted based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Candidate variant was traced in the pedigree to assess the recurrence risk. RESULTS: The karyotypes of the pregnant woman, her fetus, and affected child were 46,XX,ins(18)(p11.2q21q22), 46,X?,rec(18)dup(18)(q21q22)ins(18)(p11.2q21q22)mat and 46,XY,rec(18)del(18)(q21q22)ins(18)(p11.2q21q22)mat, respectively. Her husband was found to have a normal karyotype. CNV-seq has revealed a 19.73 Mb duplication at 18q21.2-q22.3 in the fetus and a 19.77 Mb deletion at 18q21.2-q22.3 in her child. The duplication and deletion fragments were identical to the insertional fragment in the pregnant woman. Based on the ACMG guidelines, the duplication and deletion fragments were both predicted to be pathogenic. CONCLUSION: The intrachromosomal insertion of 18q21.2-q22.3 carried by the pregnant woman had probably given rise to the 18q21.2-q22.3 duplication and deletion in the two offspring. Above finding has provided a basis for genetic counseling for this pedigree.

Genetic analysis of a Chinese pedigree with 18q21.2-q22.3 duplication and deletion in two offspring respectively resulting from a maternal intrachromosomal insertion / 中华医学遗传学杂志

OBJECTIVE@#To provide prenatal diagnosis, pedigree analysis and genetic counseling for a pregnant woman who had given birth to a child featuring global developmental delay.@*METHODS@#A pregnant woman who underwent prenatal diagnosis at the Affiliated Hospital of Southwest Medical University in August 2021 was selected as the study subject. Peripheral blood samples were collected from the woman, her husband and child, in addition with amniotic fluid sample during mid-pregnancy. Genetic variants were detected by G-banded karyotyping analysis and copy number variation sequencing (CNV-seq). Pathogenicity of the variant was predicted based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Candidate variant was traced in the pedigree to assess the recurrence risk.@*RESULTS@#The karyotypes of the pregnant woman, her fetus, and affected child were 46,XX,ins(18)(p11.2q21q22), 46,X?,rec(18)dup(18)(q21q22)ins(18)(p11.2q21q22)mat and 46,XY,rec(18)del(18)(q21q22)ins(18)(p11.2q21q22)mat, respectively. Her husband was found to have a normal karyotype. CNV-seq has revealed a 19.73 Mb duplication at 18q21.2-q22.3 in the fetus and a 19.77 Mb deletion at 18q21.2-q22.3 in her child. The duplication and deletion fragments were identical to the insertional fragment in the pregnant woman. Based on the ACMG guidelines, the duplication and deletion fragments were both predicted to be pathogenic.@*CONCLUSION@#The intrachromosomal insertion of 18q21.2-q22.3 carried by the pregnant woman had probably given rise to the 18q21.2-q22.3 duplication and deletion in the two offspring. Above finding has provided a basis for genetic counseling for this pedigree.

Genome-wide association study for Chagas Cardiomyopathy identify a new risk locus on chromosome 18 associated with an immune-related protein and transcriptional signature.

BACKGROUND: Chronic Chagas Cardiomyopathy (CCC) usually develops between 10 and 20 years after the first parasitic infection and is one of the leading causes of end-stage heart failure in Latin America. Despite the great inter-individual variability in CCC susceptibility (only 30% of infected individuals ever present CCC), there are no known predictors for disease development in those chronically infected. METHODOLOGY/PRINCIPAL FINDINGS: We describe a new susceptibility locus for CCC through a GWAS analysis in the SaMi-Trop cohort, a population-based study conducted in a Chagas endemic region from Brazil. This locus was also associated with CCC in the REDS II Study. The newly identified locus (rs34238187, OR 0.73, p-value 2.03 x 10-9) spans a haplotype of approximately 30Kb on chromosome 18 (chr18: 5028302-5057621) and is also associated with 80 different traits, most of them blood protein traits significantly enriched for immune-related biological pathways. Hi-C data show that the newly associated locus is able to interact with chromatin sites as far as 10Mb on chromosome 18 in a number of different cell types and tissues. Finally, we were able to confirm, at the tissue transcriptional level, the immune-associated blood protein signature using a multi-tissue differential gene expression and enrichment analysis. CONCLUSIONS/SIGNIFICANCE: We suggest that the newly identified locus impacts CCC risk among T cruzi infected individuals through the modulation of a downstream transcriptional and protein signature associated with host-parasite immune response. Functional characterization of the novel risk locus is warranted.

Cardiac amyloidosis: rare association of VAL142ILE and VAL50MET pathogenic variants

INTRODUCTION: Cardiac amyloidosis is a underdiagnosed cause of heart failure. Hereditary transthyretin amyloidosis can occur in more than 130pathogenic variants with variable clinical presentation depending on the type of mutation. They two main phenotypes are peripheral polyneuropathy and amyloidotic heart disease. The variant Val50t is the most prevalent in the world and most important representative of the polyneur phenotype. Val142Ile is the second most prevalent and is mostly expressed with heart disease. We describe a patient who presents a rare association of these two pathogenic variants in composed heterozygosity. Case report: A 66-year-old black male patient from Juazeiro-BA, previously healthy, with a family history of neuropathy and heart disease in two brothers who died with 64 and 73 years old. She had altered sensitivity in the tips of her fingers, hands and feet, burning pain and reduced strength in her left leg and both hands for tree years. She also reported weight loss of 9 kg in two years, dizziness when assuming an orthostatic position and early satiety. Cardiological complaints were just heart palpitations during exercise and lower limb edema. In physical examination she presented with postural hypotension, rediced grip strength and pinching movement in the fingers and atrophy of the intrinsic muscles of the hands. Electrocardiogram: left anterior fascicular block and inactive zone of inferior and anterior walls. Echocardiogram: preserved left ventricle ejection fraction (global longitudinal strain of -8.7%), grade III diastolic dysfunction and enlargement of the left ventricle wall (20mm) and interatrial septum (9mm). Pyrophosphate scintigraphy showed pergini grade 3 uptake with a 2.22 rate. Genetic sequencing demonstrated the presence of two pathogenic variants on chromosome 18, both in heterozygosity: Val50Met and VAL142Ile. CONCLUSION: an association of two pathogenic variants is rare and is associated with a more severe expression of the disease and worse prognosis. In this case the apresentation was mixed: heart disease, polyneuropathy and dysautonomia, with a predominance of the last one. Heart disease symptoms were not exuberant, perhaps because of the physical limitation of the patient. However, the uptake of pyrophosphate on scintigraphy was much more intense than usual, suggesting high degree of deposit and worse prognosis.

Case report: genetic analysis of a child with 18q deletion syndrome and developmental dysplasia of the hip.

OBJECTIVE: To analyze the genotypes and phenotypes of a child with developmental dysplasia of the hip (DDH), developmental delays, recurrent fever, hypothyroidism and cleft palate. METHODS: G-banding karyotyping analysis and next-generation sequencing (NGS) were performed for the patient. The genotypes of the parents of the patient were verified by copy number variation analysis and Sanger sequencing to determine the source of variations. RESULTS: The karyotype of the patient was 46, XX. A 10.44 Mb deletion (chr18:67562936-78005270del) at 18q22.2q23 was found by NGS. We identified 2 HSPG2 mutations (chr1: 22206699, c.2244C > A, exon 17, p.H748Q; chr1: 22157321-22157321, c.11671 + 154insA, intron). One mutation was inherited from the father, and the other was inherited from the mother. CONCLUSION: This is the first 18q deletion syndrome case accompanied by DDH. Most phenotypes of this patient, such as developmental delays and cleft palate, may be related to the 18q22.2q23 deletion, but no variants in genes related to DDH were found in this deletion region. DDH may be related to mutations of HSPG2.

Low-level complex mosaic with multiple cell lines affecting the 18q21.31q21.32 region in a patient with de novo 18q terminal deletion.

We describe a 5-year-old girl who was diagnosed at birth with 18q de novo homogeneous deletion at G-banding karyotype. Her clinical condition, characterized by hypotonia, psychomotor retardation, short stature, deafness secondary to bilateral atresia of the external auditory canals, was in agreement with the 18q deletion syndrome though presence of coloboma of a single eye only suggested a mosaic condition as an unusual sign. By combining multiple technologies including array-CGH, FISH, and WGS, we found that the terminal deletion 18q21.32q23 (21 Mb) was in segmental mosaicism of the proximal region 18q21.31q21.32 (2.7 Mb), which showed a variable number of copies: one, two, or three, in 7, 41 and 55% of the cells respectively. Breakpoint junction analysis demonstrated the presence of an inv-dup del (18q) with a disomic segment of 4.7 kb between the inverted and non-inverted copies of the duplicated region 18q21.31q21.32. From these results, we propose that all three types of abnormal chr18 (the inv-dup del and the two 18q terminal deletions of different sizes) arisen from breaks in a dicentric mirror chromosome 18q, either in more than one embryo cell or from subsequent breaking-fusion-bridge cycles. The duplication region was with identical polymorphisms as in all non-recurrent inv-dup del rearrangements though, in contrast with most of them, the 18q abnormality was of maternal origin. Taking into account that distal 18q deletions are not rarely associated with inv-dup del(18q) cell lines, and that the non-disjunction of chromosome 18 takes place especially at maternal meiosis II rather than meiosis I, multiple rescue events starting from trisomic zygotes could be considered alternative to the postmitotic ones. From the clinical point of view, our case, as well as those of del(18q) in mosaic with the dic(18q), shows that the final phenotype is the sum of the different cell lines that acted on embryonic development with signs typical of both the 18q deletion syndrome and trisomy 18. Asymmetrical malformations, such as coloboma of the iris only in the right eye, confirm the underlying mosaicism regardless of whether it is still detectable in the blood.

Prenatal diagnosis and molecular cytogenetic characterization of an inherited microdeletion of 18q12.3 encompassing SETBP1.

The 18q12.3 region contains the SET binding protein 1 (SETBP1) gene. SETBP1 mutations or deletions are associated with Schinzel-Giedion syndrome or intellectual developmental disorder, autosomal dominant 29. We report the prenatal diagnosis and genetic counseling of a patient with a maternally inherited 18q12.3 microdeletion. In this family, the mother and son carried the same microdeletion. Chromosomal microdeletions and microduplications are difficult to detect using conventional cytogenetics, whereas the combination of prenatal ultrasound, karyotype analysis, chromosomal microarray analysis, and genetic counseling is helpful for the prenatal diagnosis of chromosomal microdeletions/microduplications.

Karyotype patterns, clinical features, and parental ages of three predominant live born autosomal trisomies of Northeast Malaysia.

Chromosomal abnormality is one of the causes of congenital disorders among newborns. Despite aneuploidy being the major cause of first trimester miscarriages, very few aneuploidies such as trisomies of chromosomes 13, 18 and 21 survive to birth. The results of 4,064 patients referred for cytogenetic analysis at Human Genome Centre, Universiti Sains Malaysia, Kelantan, Malaysia between 2008 and 2019 were reviewed. We retrospectively investigated the karyotype patterns, clinical features and parental ages of the three common live-born autosomal trisomies such as trisomy 13, trisomy 18 and trisomy 21. The relative frequency of cases with the total sample received and cultured was calculated in each group and compared with those reported elsewhere. Between 2008 and 2019, a total of 1034 live-born trisomic cases which accounted for 25.4% of the 4064 total referred cases and 73.7% of 1403 suspected trisomy cases, were identified, with age ranging from newborns to 57 years. Down syndrome was the commonest aneuploidy (857 cases; 21.1%) followed by Edwards syndrome (133 cases; 3.3%) and Patau syndrome (44 cases; 1.1%). The number of diagnosed cases for each of the trisomies was fairly stable from year to year. About two-thirds of both maternal and paternal ages were ≥ 35 years. This is the first cytogenetic report on the common live-born autosomal trisomies in the North-Eastern region of Malaysia. The prevalence of trisomies 21 was found to be higher compared to an earlier study in the North-Western region of Malaysia, wherein also, advanced maternal age was a significant risk factor.

Trisomy 20p/monosomy 18p associated with congenital bilateral perisylvian syndrome.

We report the association, not previously described, between trisomy 20/ monosomy 18 and congenital bilateral perisylvian syndrome (CBPS), a condition featuring intellectual disability, epilepsy, oro-motor dysfunction and bilateral perisylvian polymicrogyria (BPP) in a 29-year-old individual. Detailed clinical evaluation, long-term EEG and EEG analysis by means of electrical source imaging (ESI), 3T MRI and array-CGH were performed. Clinical examination showed moderate/severe intellectual disability, dysmorphic features, oro-motor dysfunction, short stature, abnormal hands and feet, bradykinesia and abnormal posture. The patient had suffered from drug-resistant epilepsy since infancy. Brain MRI showed that BPP was consistent with CBPS. Additional imaging features revealed corpus callosum and cerebellar hypoplasia and fusion of the C1-C2 vertebrae. Ictal EEG and ESI documented tonic seizures originating from the right polymicrogyric cortex. Facial gestalt included dysmorphic features reported in patients with 18- and 20+ chromosomal rearrangements. Array-CGH showed an unbalanced translocation, arr(18p)x1(20p)x3. In conclusion, we provide a detailed electro-clinical and MRI description of a novel condition characterized by the association between trisomy 20p/monosomy 18p and CBPS, also illustrating its clinical evolution into adulthood. This information may help paediatricians, neurologists and geneticists to better counsel families about the developmental prognosis of this rare unbalanced chromosomal rearrangement.

Oral Care in a Patient with Long Arm Deletion Syndrome of Chromosome 18: A Narrative Review and Case Presentation.

BACKGROUND Long arm (q) deletion syndrome of chromosome 18 is a congenital chromosomal disorder. The specialist dental management of patients with 18q deletion is a challenge, as these individuals fall into the category of patients with special needs. The aim of this work was to describe the surgical and dental management in hospital of a patient with long arm deletion syndrome of chromosome 18 (18q). CASE REPORT An 8-year-old patient with deletion syndrome of chromosome 18 (18q) was referred to the Department of Dentistry and Oral Surgery. The patient presented dental pain and difficult feeding. The examination of the oral cavity revealed a destructive carious lesion of the lower right second deciduous molar and the need to perform a frenectomy due to the short lingual frenulum, which limited the movements of the tongue. Given the complex management of the patient, it was necessary to carry out surgical procedures in the operating room. Frenectomies of the lower labial and lingual frenulum were carried out with the aid of an electric scalpel with an ultra-sharp microdissection needle. At 2-month follow-up, the patient presented with good extraction site healing and satisfactory lingual mobility, along with improvements of speech and feeding. CONCLUSIONS Dental involvement in patients with deletion syndrome of the long arm of chromosome 18 is poorly documented in the literature. The hospital regimen appears to be the criterion standard for the management of the patient with long arm deletion syndrome of chromosome 18.

Pulmonary artery sling in a 22-month-old boy with 18q deletion syndrome: A rare but possible association.

The 18q deletion syndrome is a rare genetic condition characterized by a large variability in clinical phenotype and severity. Congenital heart diseases have been described by several previous reports, most commonly including pulmonary valve anomalies and septal defects. We describe a new case of a 22-month-old boy affected by 18q del syndrome found to have a symptomatic pulmonary artery sling. This study reports a new case of pulmonary artery sling associated with 18q del syndrome, providing an alert for pediatric cardiologists about less common cardiovascular anomalies, which can easily be missed, allowing for early diagnosis and appropriate care.