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BMC Medical Genomics Oct 2023Whole-exome sequencing (WES) significantly improves the diagnosis of the etiology of fetal structural anomalies. This study aims to evaluate the diagnostic value of...
BACKGROUND
Whole-exome sequencing (WES) significantly improves the diagnosis of the etiology of fetal structural anomalies. This study aims to evaluate the diagnostic value of prenatal WES and to investigate the pathogenic variants in structurally abnormal fetuses.
METHODS
We recruited 144 fetuses with structural anomalies between 14 and 2020 and 15 December 2021 in the study. Genetic screening was performed by WES combined with karyotyping and chromosomal microarray analysis. The molecular diagnostic yield of prenatal WES for each type of fetal structural anomaly and the identified pathogenic genes and mutations were reported.
RESULTS
In this study, we retrospectively analyzed the clinical and genetic data of 145 structurally anomalous fetuses. These cases were classified into 9 phenotypic classes based on antenatal ultrasound findings. Thirty-eight pathogenic variants in 24 genes were identified in 35 of the 145 cases, including 14 novel variants in 13 genes (EP300, MYH3, TSC2, MMP9, CPLANE1, INVS, COL1A1, EYA1, TTC21B, MKS1, COL11A2, PDHA1 and L1CAM). Five additional pathogenic variants were classified as incidental findings. Our study showed that the overall diagnosis rate of WES was 28.1% (27/96) in the parent-fetus trio cases and 16.3% (8/49) in the proband-only cases. Fetuses with musculoskeletal anomalies had the highest diagnostic yield (51.4%, 19/37). In addition, FGFR3 and COL1A1 were the most common pathogenic genes.
CONCLUSIONS
Our work expands the mutation spectrum of the genes associated with fetal structural anomalies and provides valuable information for future parental genetic counselling and pregnancy management of the structurally anomalous fetuses.
Topics: Female; Humans; Pregnancy; East Asian People; Exome Sequencing; Fetus; Pregnancy Trimester, First; Prenatal Diagnosis; Retrospective Studies; Ultrasonography, Prenatal; Congenital Abnormalities
PubMed: 37880672
DOI: 10.1186/s12920-023-01697-3 -
The Spine Journal : Official Journal of... 2005The spine is a complex and vital structure. Its function includes not only structural support of the body as a whole, but it also serves as a conduit for safe passage of... (Review)
Review
BACKGROUND CONTEXT
The spine is a complex and vital structure. Its function includes not only structural support of the body as a whole, but it also serves as a conduit for safe passage of the neural elements while allowing proper interaction with the brain. Anatomically, a variety of tissue types are represented in the spine. Embryologically, a detailed cascade of events must occur to result in the proper formation of both the musculoskeletal and neural elements of the spine. Alterations in these embryologic steps can result in one or more congenital abnormalities of the spine. Other body systems forming at the same time embryologically can be affected as well, resulting in associated defects in the cardiopulmonary system and the gastrointestinal and genitourinary tracts.
PURPOSE
This article is to serve as a review of the basic embryonic development of the spine. We will discuss the common congenital anomalies of the spine, including their clinical presentation, as examples of errors of this basic embryologic process.
STUDY DESIGN/SETTING
Review of the current literature on the embryology of the spine and associated congenital abnormalities.
METHODS
A literature search was performed on the embryology of the spine and associated congenital abnormalities.
RESULTS
Development of the spine is a complex event involving genes, signaling pathways and numerous metabolic processes. Various abnormalities are associated with errors in this process.
CONCLUSION
Physicians treating patients with congenital spinal deformities should have an understanding of normal embryologic development as well as common associated abnormalities.
Topics: Humans; Klippel-Feil Syndrome; Neural Tube Defects; Spinal Curvatures; Spinal Dysraphism; Spine; Spondylolisthesis
PubMed: 16153587
DOI: 10.1016/j.spinee.2004.10.044 -
The Journal of Molecular Diagnostics :... Jul 2017Somatic variants have been well described in tumorigenesis; however, they are only recently appreciated in other human disorders, such as mosaic overgrowth syndromes.... (Review)
Review
Somatic variants have been well described in tumorigenesis; however, they are only recently appreciated in other human disorders, such as mosaic overgrowth syndromes. Although overgrowth is a manifestation in many genetic syndromes, not all overgrowth syndromes are inherited. Mosaic somatic variants have been lately described in several overgrowth disorders, such as Proteus syndrome, CLOVES (congenital, lipomatous, overgrowth, vascular malformations, epidermal nevi, and spinal/skeletal anomalies and/or scoliosis) syndrome, and megalencephalyepolymicrogyria-polydactyly-hydrocephalus syndrome. These syndromes are caused by somatic variants in the genes associated with the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin pathway, resulting in a spectrum of overgrowth syndromes with overlapping features that could be difficult to distinguish based on phenotypic presentations alone. In addition, Sanger sequencing is ineffective for the detection of a causal variant because of the mosaic nature of these variants, whereas targeted next-generation sequencing technology offers a deeper sequencing coverage and allows the detection of low-level mosaicism. Recent studies have shown that the causal variants are only present in the affected tissues in most cases, and can be enriched by in vitro tissue culture. In this review, we describe several mosaic somatic overgrowth syndromes caused by variants in genes of the phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin signaling pathway, their phenotypic and molecular spectrum, and the clinical utility of next-generation sequencing technology in the diagnosis of these disorders.
Topics: Animals; Clinical Trials as Topic; Female; Fingers; Genetic Testing; Genetic Variation; High-Throughput Nucleotide Sequencing; Humans; Hydrocephalus; Hypoglycemia; Limb Deformities, Congenital; Lipoma; Malformations of Cortical Development; Mosaicism; Musculoskeletal Abnormalities; Nevus; Phosphatidylinositol 3-Kinase; Polydactyly; Proto-Oncogene Proteins c-akt; Signal Transduction; TOR Serine-Threonine Kinases; Vascular Malformations
PubMed: 28502730
DOI: 10.1016/j.jmoldx.2017.04.001 -
The Journal of Toxicological Sciences Apr 2014Possible teratogenicity of 3 different asbestos (crocidolite, chrysotile and amosite) was assessed in CD1(ICR) mice. Dams on day 9 of gestation were given a single...
Possible teratogenicity of 3 different asbestos (crocidolite, chrysotile and amosite) was assessed in CD1(ICR) mice. Dams on day 9 of gestation were given a single intraperitoneal administration at dose of 40 mg/kg body weight of asbestos suspended in 2% sodium carboxymethyl cellulose solution in phosphate buffered saline, while dams in the control group were given vehicle (10 ml/kg body weight). Dams and fetuses were examined on day 18 of gestation. To compare with the control group, the mean percentage of live fetuses in implantations in the group given crocidolite and the incidence of dams with early dead fetuses in the groups given chrysotile or amosite were increased. While no external or skeletal malformation was observed in the control group, the incidence of external malformation (mainly reduction deformity of limb) in the group given amosite, and the incidences of skeletal malformation (mainly fusion of vertebrae) in the all dosed groups were significantly increased. The result indicated that asbestos (crocidolite, chrysotile and amosite) have fetotoxicity and teratogenicity in mice.
Topics: Abnormalities, Multiple; Animals; Asbestos, Amosite; Asbestos, Crocidolite; Asbestos, Serpentine; Female; Fetus; Gestational Age; Incidence; Injections, Intraperitoneal; Limb Deformities, Congenital; Maternal-Fetal Exchange; Mice; Mice, Inbred ICR; Musculoskeletal Abnormalities; Pregnancy; Specific Pathogen-Free Organisms; Teratogenesis
PubMed: 24646718
DOI: 10.2131/jts.39.363 -
Acta Paediatrica Academiae Scientiarum... 1982The so-called congenital postural deformities were evaluated in the material of the Hungarian Congenital Malformation Registry, 1970-1976. Seven categories of postural...
The so-called congenital postural deformities were evaluated in the material of the Hungarian Congenital Malformation Registry, 1970-1976. Seven categories of postural deformities: dislocation of the hip, clubfoot, torticollis, musculoskeletal, other limb, face-nose and auricular were separated. The occurrence of the combination of dislocation of the hip, clubfoot and torticollis is manifold of random combination. These three postural deformities, however, are not associated more often with other nonpostural type abnormalities. Thus the congenital postural deformity association composed of two or more combinations of dislocation of the hip, clubfoot and torticollis without other major congenital abnormalities is treated as a provisional entity. Its birth prevalence is 0.4 per 1000 total births thus after Down syndrome it is the second common type of multiple congenital abnormalities. The aetiology and its higher sib-occurrence are explained by intrauterine maternal moulding factors.
Topics: Abnormalities, Multiple; Clubfoot; Congenital Abnormalities; Female; Hip Dislocation, Congenital; Humans; Hungary; Infant, Newborn; Male; Musculoskeletal Abnormalities; Posture; Registries; Torticollis
PubMed: 7170954
DOI: No ID Found -
African Journal of Reproductive Health Sep 2020Nigeria has a large number of congenital disorders (CD). For instance, two out of every hundred children born in Nigeria have sickle cell disorders (SCD). Making Nigeria... (Review)
Review
Nigeria has a large number of congenital disorders (CD). For instance, two out of every hundred children born in Nigeria have sickle cell disorders (SCD). Making Nigeria the country with the highest incidence of SCD. This article reviews the prevalence of CD in Nigeria; with emphasis on those having a heavy statistical burden on the country, the availability of community genetics services in Nigeria and the efforts being made to tackle the challenges of CD. A systematic review of birth prevalence of congenital malformations (CM) in Nigeria was done through a literature search, with no time restriction for publication dates. Only studies that included the birth prevalence of CM were included. Eligible studies with incorrect or missing data were excluded. This revealed a dearth of data on CD in Nigeria, as in most Low- and Middle-Income Countries. A predominance of CM of the musculoskeletal and gastrointestinal systems was found in Nigeria. However, the pattern of CM in the South-South region was more of the central nervous system. There is scarcity of resources to address the challenges of CD in Nigeria with feeble government assistance. Meanwhile, 70% of CD can be prevented and adequately managed by well implemented community genetics services.
Topics: Anemia, Sickle Cell; Central Nervous System; Community Health Services; Congenital Abnormalities; Genetic Counseling; Genetic Diseases, Inborn; Genetic Services; Humans; Infant, Newborn; Musculoskeletal Abnormalities; Nigeria
PubMed: 34077139
DOI: 10.29063/ajrh2020/v24i3.18 -
Surgical and Radiologic Anatomy : SRA Apr 2015The tendon of the extensor indicis (EI) is frequently used to restore the loss of function in other digits. However, it shows many variations which include splitting of... (Meta-Analysis)
Meta-Analysis Review
The tendon of the extensor indicis (EI) is frequently used to restore the loss of function in other digits. However, it shows many variations which include splitting of the extensor indicis proprius (EIP) into two or three distal slips, attachment to fingers other than the index such as the extensor medii proprius (EMP), attachment onto the index and the third finger such as the extensor indicis et medii communis, or attachment to both the index and the thumb such as the extensor pollicis et indicis (EPI). This systematic review gathers the available data on the prevalence of EI tendon and its variation in the hand. Twenty-nine cadaveric studies met the inclusion criteria with a total of 3858 hands. Meta-analysis results yielded an overall pooled prevalence estimate (PPE) of EI of 96.5% and PPEs of 92.6, 7.2 and 0.3% for the single-, double- and triple-slip EIP, respectively. The single-slip EIP is frequently inserted on the ulnar side of the extensor digitorum communis of the index (EDC-index) in 98.3%. The double-slip EIP is located on the ulnar side of the EDC-index in 53.5%, on its radial side in 17% and on both sides in 28.7%. Indian populations showed the highest rate of single-slip EIP and the lowest rate of double-slip EIP when compared to Japanese, Europeans and North Americans. The pooled prevalence of EMP, EMIC and EPI were 3.7, 1.6 and 0.75%, respectively. Knowledge of the variants of the EI tendon and their prevalence should help surgeons in correctly choosing the tendon to transfer in hand surgery.
Topics: Cadaver; Dissection; Female; Finger Joint; Hand; Hand Deformities, Congenital; Humans; Male; Musculoskeletal Abnormalities; Prevalence; Tendons
PubMed: 25096501
DOI: 10.1007/s00276-014-1352-0 -
Journal of Rehabilitation Medicine Feb 2013Asymmetrical skull deformity is frequently seen in children with cerebral palsy, and may contribute to postural abnormalities and deformities. The aim of this...
OBJECTIVE
Asymmetrical skull deformity is frequently seen in children with cerebral palsy, and may contribute to postural abnormalities and deformities. The aim of this cross-sectional- survey was to determine the frequency of asymmetrical skull deformity and its correlation with clinical parameters.
METHODS
A 10-item checklist for asymmetrical skull deformity, postural abnormalities, and deformities was developed, and its inter-rater reliability was tested. A total of 110 participants aged 1-18 years (mean age 9.3 years (standard deviation 4.7)) was assessed using the checklist. The frequency of asymmetrical skull deformity was analysed and related to the Gross Motor Function Classification System (GMFCS), postural abnormalities, and deformities.
RESULTS
The reliability of the checklist was satisfactory (κ > 0.8). Asymmetrical skull deformity was observed in 44 children, 24 showing right and 20 showing left flat occipital deformity. Its frequency was significantly related to GMFCS and with the patterns of asymmetrical posture and deformities (p < 0.05). Children with right flat occipital asymmetrical skull deformity showed predominantly rightward facial direction and right-side-dominant asymmetrical tonic neck reflex, left convex scoliosis, right-side-elevated pelvic obliquity, and left-sided hip dislocation. Those with left flat occipital asymmetrical skull deformity demonstrated the reverse tendency.
CONCLUSION
Asymmetrical skull deformity is frequent in cerebral palsy and closely related to asymmetrical posture and deformities. This information will be useful to manage these problems.
Topics: Adolescent; Bone Diseases; Cerebral Palsy; Checklist; Child; Child, Preschool; Craniofacial Abnormalities; Cross-Sectional Studies; Face; Female; Hip; Hip Dislocation; Humans; Infant; Male; Musculoskeletal Abnormalities; Neck; Occipital Bone; Pelvis; Posture; Reflex; Reproducibility of Results; Scoliosis; Spine
PubMed: 23138456
DOI: 10.2340/16501977-1081 -
Neurological Research Oct 2004Tethered Cord Syndrome (TCS) is a stretch-induced functional disorder of the spinal cord that often develops and presents in childhood in association with spinal... (Review)
Review
Tethered Cord Syndrome (TCS) is a stretch-induced functional disorder of the spinal cord that often develops and presents in childhood in association with spinal dysraphism. While the subtlety with which TCS can present makes it challenging to diagnose, awareness of the common neurological, musculoskeletal and urologic symptoms are of great value to the clinician, and can aid timely referral for neurosurgical evaluation. This article reviews these symptoms, as well as the clinical and radiological findings of the most common dysraphic conditions associated with TCS.
Topics: Cauda Equina; Child; Congenital Abnormalities; Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Meningomyelocele; Models, Neurological; Musculoskeletal Diseases; Neural Tube Defects; Neurologic Examination; Radiography; Spinal Cord; Spinal Cord Compression; Spinal Dysraphism; Urologic Diseases
PubMed: 15494116
DOI: 10.1179/016164104225017974 -
BMJ Case Reports Jan 2019We present here two-term neonates presenting with right lower limb hypertrophy, a port-wine stain, acral abnormalities and clubfeet. These neonates had overlapping... (Review)
Review
We present here two-term neonates presenting with right lower limb hypertrophy, a port-wine stain, acral abnormalities and clubfeet. These neonates had overlapping features of Klippel Trenaunay syndrome and congenital lipomatous overgrowth, vascular malformation, epidermal nevi and scoliosis/skeletal abnormalities. Such overgrowth syndrome has not been previously described in the literature. Both the neonates are doing well and are under regular follow-up.
Topics: Congenital Abnormalities; Disease Management; Humans; Infant, Newborn; Klippel-Trenaunay-Weber Syndrome; Male; Musculoskeletal Abnormalities; Nevus; Port-Wine Stain
PubMed: 30658999
DOI: 10.1136/bcr-2018-225640