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The Journal of Hand Surgery... Aug 2022Laurin-Sandrow syndrome (LSS) is an extremely rare syndrome of mirror hand and leg with less than 20 cases reported in literature. The syndrome has been attributed to a... (Review)
Review
Laurin-Sandrow syndrome (LSS) is an extremely rare syndrome of mirror hand and leg with less than 20 cases reported in literature. The syndrome has been attributed to a mutation in the MIPOL-1 (mirror-image polydactyly) gene located on locus 14q13.3-q21 coding for CCDC193 (coiled-coli domain containing 193) protein. It is characterised by limb, facial and central nervous system anomalies with the most constant being fibular dimelia with fibular ray duplication, polydactyly with secondary deformities of fixed equinus, knee joint instability and flexion deformity. It is associated less frequently with ulnar dimelia, thumb aplasia/hypoplasia, ulnar ray duplication, symbrachypolydactyly, 'rosette' hands, facial dysmorphism like hypertelorism, broad columella and flat nose, CNS anomalies like aplasia/hypoplasia of corpus callosum, hydrocephalus and muscular dystonia. We report a 2-year-old male child with LSS and perform a literature review to expound on this rare syndrome. Level V (Therapeutic).
Topics: Abnormalities, Multiple; Child; Child, Preschool; Ectromelia; Foot Deformities, Congenital; Hand Deformities, Congenital; Humans; Male; Nose; Syndrome
PubMed: 35965362
DOI: 10.1142/S2424835522720389 -
Archives of Disease in Childhood. Fetal... Jan 2021
Topics: Breast Feeding; Congenital Abnormalities; Diagnosis, Differential; Female; Humans; Infant, Newborn; Laryngomalacia; Larynx; Polyhydramnios; Pregnancy; Tachycardia, Supraventricular
PubMed: 32788392
DOI: 10.1136/archdischild-2020-319435 -
Fetal Diagnosis and Therapy 2023Sprengel's deformity is a rare congenital anomaly of the shoulder rim. It is the most common congenital anomaly of the shoulder, associated with cosmetic deformity and...
INTRODUCTION
Sprengel's deformity is a rare congenital anomaly of the shoulder rim. It is the most common congenital anomaly of the shoulder, associated with cosmetic deformity and abnormal shoulder function. Nonsurgical management can be considered for mild cases. Surgical intervention is indicated in moderate to severe cases with the goal of improving cosmetic appearance and function. The best surgical results are obtained in children aged 3-8 years. Correct diagnosis is very important because Sprengel's deformity can be accompanied by additional abnormalities, even in mild cases, and lack of a diagnosis delays proper treatment of the child. The severity of the defect may progress, so it is important to correctly identify children with Sprengel's deformity, even those with a mild form of the defect.
CASE PRESENTATION
We report a case of prenatal sonographic diagnosis of Sprengel's deformity with additional features, as yet undescribed and missed - although visible - on prenatal magnetic resonance imaging (MRI). Cesarean delivery was performed due to preterm rupture of membranes, and a postnatal MRI confirmed the unusual constellation of Sprengel's anomaly with lateral meningocele, vestigial posterior meningocele, and lipoma tethering of the cord to the dural sac at the cervical-thoracic junction.
CONCLUSION
Diagnosis of Sprengel's deformity is possible with prenatal ultrasound. Asymmetry of the cervical spine, discontinuity of the vertebral arch and abnormal vertebral bodies, as well as the asymmetric position of the shoulder blades with the presence of an omovertebral bone are signs that can help diagnose the defect.
Topics: Child; Infant, Newborn; Female; Pregnancy; Humans; Meningocele; Scapula; Shoulder Joint; Magnetic Resonance Imaging; Congenital Abnormalities
PubMed: 37393895
DOI: 10.1159/000531677 -
Urology Mar 2021To describe 5 cases with complete urinary bladder duplication, their associated conditions, and their respective treatment. Urinary bladder duplication is an extremely...
OBJECTIVE
To describe 5 cases with complete urinary bladder duplication, their associated conditions, and their respective treatment. Urinary bladder duplication is an extremely rare congenital anomaly of the urinary system. So far about 70 cases have been published in the English literature, most of them as case reports and a few case series.
METHODS AND RESULTS
All consecutive patients with bladder duplication treated at our institution between 2000 and 2015 were included. Patient records were retrospectively analyzed, and 5 patients with urinary bladder duplication were identified (see Summary Figure). Two patients were male. All duplications were recognized by health care providers. In 1 case recognition was prenatal (MRI in utero at 22 weeks of gestation), the latest recognition was at 12 months of age. A voiding cystourethrography was performed in 4 patients to confirm the diagnosis. In 4 patients the bladder duplication could be classified according to Abrahamson with 3 complete reduplications and one complete sagittal septum. All patients suffered from associated congenital diseases, but only one patient had urinary tract infections. Surgical treatment was only performed in one patient. Median follow-up was 34 months.
DISCUSSION
Urinary bladder duplications reflect extremely seldom disorders that are almost always associated with other congenital anomalies. Treatment depends on patients' symptoms and associated conditions and hence needs to be individualized to each patient.
Topics: Congenital Abnormalities; Female; Humans; Infant; Infant, Newborn; Male; Retrospective Studies; Urinary Bladder
PubMed: 33189736
DOI: 10.1016/j.urology.2020.11.001 -
Journal of Assisted Reproduction and... Aug 2019While mitotic errors commonly cause aneuploid clones soon after conception, the embryos often normalize as clones are rapidly eliminated. Although generally considered... (Review)
Review
While mitotic errors commonly cause aneuploid clones soon after conception, the embryos often normalize as clones are rapidly eliminated. Although generally considered benign, evidence suggests clone elimination as the primary cause of the vertebral, ano-rectal, cardiac, tracheo-esophageal, renal, and limb (VACTERL) association of anomalies, and possibly other adverse outcomes as well. Here, clone elimination-related development disruption at specific locations is used as the basis of a comprehensive theoretical VACTERL association model that also elucidates mitotic mosaic aneuploidy effects. For the association, the model explains random temporal and spatial origins during a limited time frame and overlapping clusters of component anomalies. It supports early developmental effects involving the stage of determination, where the position in a specific morphogen field controls what a cell will become and where it will be located. Developmental properties related to determination also create specific vulnerabilities to the midline and distal defects, the latter explaining exclusively radial and tibial defects with duplications and deficiencies. The model also supports isolated anomalies as part of the association and, for mosaic mitotic aneuploidy, indicates that clone elimination nears completion at the time of lower limb determination. Although mosaic clone elimination may cause other defects, occurrences in different developmental fields separate them from VACTERL anomalies. Clone elimination may also be related to risks for a single umbilical artery and for non-structural adverse pregnancy outcomes such as losses, prematurity, and growth delays, while a paucity of clone lethality in non-humans explains the rarity of the association and of single umbilical arteries in animals.
Topics: Abnormalities, Multiple; Anal Canal; Aneuploidy; Animals; Embryo, Mammalian; Embryo, Nonmammalian; Esophagus; Female; Heart Defects, Congenital; Kidney; Limb Deformities, Congenital; Pregnancy; Spine; Trachea
PubMed: 31129863
DOI: 10.1007/s10815-019-01485-y -
BMJ Case Reports Jan 2021We report a child, diagnosed with Coffin-Siris syndrome (CSS), with chronic right otorrhoea. CT and DR-MRI were performed to further investigate, diagnose and determine...
We report a child, diagnosed with Coffin-Siris syndrome (CSS), with chronic right otorrhoea. CT and DR-MRI were performed to further investigate, diagnose and determine relevant surgical anatomy. CT temporal bones assessment was performed, and the measurements compared with previously published data for normal temporal bone anatomy. These comparisons highlighted various differences which were not initially expected; it showed that there were multiple inner ear abnormalities in addition to middle ear disease. This case highlights the importance of considering temporal bone abnormalities in all children with CSS or any dysmorphia, when they may require mastoid procedures. Reviewing the management of this case provides relevant learning opportunities for both primary, secondary and tertiary care institutions.
Topics: Abnormalities, Multiple; Bone Diseases, Developmental; Child; Face; Hand Deformities, Congenital; Humans; Intellectual Disability; Magnetic Resonance Imaging; Male; Micrognathism; Neck; Temporal Bone; Tomography, X-Ray Computed
PubMed: 33461995
DOI: 10.1136/bcr-2020-236139 -
Birth Defects Research Nov 2019While there is strong evidence that genetic risk factors play an important role in the etiologies of structural birth defects, compared to other diseases, there have... (Review)
Review
BACKGROUND
While there is strong evidence that genetic risk factors play an important role in the etiologies of structural birth defects, compared to other diseases, there have been relatively few genome-wide association studies (GWAS) of these conditions. We reviewed the current landscape of GWAS conducted for birth defects, noting novel insights, and future directions.
METHODS
This article reviews the literature with regard to GWAS of structural birth defects. Key defects included in this review include oral clefts, congenital heart defects (CHDs), biliary atresia, pyloric stenosis, hypospadias, craniosynostosis, and clubfoot. Additionally, other issues related to GWAS are considered, including the assessment of polygenic risk scores and issues related to genetic ancestry, as well as utilizing genome-wide single nucleotide polymorphism array data to evaluate gene-environment interactions and Mendelian randomization.
RESULTS
For some birth defects, including oral clefts and CHDs, several novel susceptibility loci have been identified and replicated through GWAS, including 8q24 for oral clefts, DGKK for hypospadias, and 4p16 for CHDs. Relatively common birth defects for which there are currently no published GWAS include neural tube defects, anotia/microtia, anophthalmia/microphthalmia, gastroschisis, and omphalocele.
CONCLUSIONS
Overall, GWAS have been successful in identifying several novel susceptibility genes and genomic regions for structural birth defects. These findings have provided new insights into the etiologies of these phenotypes. However, GWAS have been underutilized for understanding the genetic etiologies of several birth defects.
Topics: Cardiovascular Abnormalities; Congenital Abnormalities; Eye Abnormalities; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Musculoskeletal Abnormalities; Nervous System Malformations; Otorhinolaryngologic Diseases
PubMed: 31654503
DOI: 10.1002/bdr2.1606 -
American Journal of Obstetrics and... Jun 2021
Topics: Congenital Abnormalities; Female; Gynecology; History, 21st Century; Humans; New York; Obstetrics; Paris; Pregnancy; Ultrasonography, Prenatal
PubMed: 33823151
DOI: 10.1016/j.ajog.2021.03.042 -
Ultrasound in Obstetrics & Gynecology :... May 2024The identification of structural variants and single-nucleotide variants is essential in finding molecular etiologies of monogenic genetic disorders. Whole-genome...
OBJECTIVES
The identification of structural variants and single-nucleotide variants is essential in finding molecular etiologies of monogenic genetic disorders. Whole-genome sequencing (WGS) is becoming more widespread in genetic disease diagnosis. However, data on its clinical utility remain limited in prenatal practice. We aimed to expand our understanding of implementing WGS in the genetic diagnosis of fetal structural anomalies.
METHODS
We employed trio WGS with a minimum coverage of 40× on the MGI DNBSEQ-T7 platform in a cohort of 17 fetuses presenting with aberrations detected by ultrasound, but uninformative findings of standard chromosomal microarray analysis (CMA) and exome sequencing (ES).
RESULTS
Causative genetic variants were identified in two families, with an increased diagnostic yield of 11.8% (2/17). Both were exon-level copy-number variants of small size (3.03 kb and 5.16 kb) and beyond the detection thresholds of CMA and ES. Moreover, to the best of our knowledge, we have described the first prenatal instance of the association of FGF8 with holoprosencephaly and facial deformities.
CONCLUSIONS
Our analysis demonstrates the clinical value of WGS in the diagnosis of the underlying etiology of fetuses with structural abnormalities, when routine genetic tests have failed to provide a diagnosis. Additionally, the novel variants and new fetal manifestations have expanded the mutational and phenotypic spectrums of BBS9 and FGF8. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Humans; Female; Pregnancy; Whole Genome Sequencing; Phenotype; DNA Copy Number Variations; Prenatal Diagnosis; Ultrasonography, Prenatal; Adult; Genotype; Genetic Testing; Exome Sequencing; Fetus; Congenital Abnormalities; Holoprosencephaly
PubMed: 37842862
DOI: 10.1002/uog.27517 -
American Journal of Medical Genetics.... Sep 2021Now in its 7th edition, Smith's Recognizable Patterns of Human Malformation was first published in 1970. This 1st edition comprised 135 "dysmorphic syndromes of multiple... (Review)
Review
Now in its 7th edition, Smith's Recognizable Patterns of Human Malformation was first published in 1970. This 1st edition comprised 135 "dysmorphic syndromes of multiple primary defects" and 12 "single syndromic malformations resulting in secondary defects." Of the former, other than a few chromosomal and environmental disorders, most were heritable conditions of then unknown etiology. In 2021, the majority of these conditions are now "solved," a notable exception is Hallermann-Streiff syndrome. The "solved" conditions were typically clinically delineated decades prior to understanding the underlying etiology, which rarely required recent technologies such as exome sequencing (ES) to elucidate. The 7th edition includes nearly 300 syndromes, sequences, and associations. An increasing number of conditions first appearing in the latest editions are sporadic, with many solved using either array CGH or ES. We have reviewed all syndromes that have appeared in "Smith's" with a focus on inheritance, heterogeneity, and year and method of etiologic discovery. Several themes emerge. Genetic heterogeneity and pleiotropy of genes are frequent. Several of the currently "unresolved" syndromes are clinically diverse such as Dubowitz syndrome. Multiple recurrent constellations of embryonic malformations, with VACTERL association as a paradigm, are increasingly likely to have a shared pathogenesis requiring further study.
Topics: Abnormalities, Multiple; Chromosomes, Human; Congenital Abnormalities; Gene-Environment Interaction; Genetic Predisposition to Disease; History, 20th Century; History, 21st Century; Humans
PubMed: 33951288
DOI: 10.1002/ajmg.a.62240