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Frontiers in Pediatrics 2023Prenatal sonographic evidence of large, echogenic, or cystic kidneys may indicate any one of a diverse set of disorders including renal ciliopathies, congenital...
INTRODUCTION
Prenatal sonographic evidence of large, echogenic, or cystic kidneys may indicate any one of a diverse set of disorders including renal ciliopathies, congenital anomalies of the kidney and urinary tract (CAKUT), or multisystem syndromic disorders. Systematic transition planning for these infants from detection to post-natal nephrology management remains to be established.
AIM OF THE WORK
We sought to evaluate the presentation and transition planning for infants identified with bilateral renal cystic disease.
METHODS
Our retrospective observational study identified 72 pregnancies with bilateral renal cystic disease in a single center from 2012 to 2022; 13 of which had a confirmed renal ciliopathy disorder. Clinical and imaging data, genetic test results, and documentation of postnatal follow-up were collected and compared.
RESULTS
In our suspected renal ciliopathy cohort ( = 17), autosomal recessive polycystic disease (ARPKD) was the most common diagnosis ( = 4), followed by Bardet-Biedl syndrome (BBS, = 3), autosomal dominant polycystic disease (ADPKD, = 2), -related disease ( = 2), and Meckel-Gruber syndrome (MKS, = 2). Four cases were not genetically resolved. Anhydramnios was observed primarily in fetuses with ARPKD ( = 3). Polydactyly ( = 3) was detected only in patients with BBS and MKS, cardiac defects ( = 6) were identified in fetuses with ARPKD ( = 3), MKS ( = 2), and BBS ( = 1), and abnormalities of the CNS ( = 5) were observed in patients with ARPKD ( = 1), MKS ( = 2), and BBS ( = 3). In general, documentation of transition planning was incomplete, with post-natal nephrology management plans established primarily for infants with renal ciliopathies ( = 11/13; 85%).
CONCLUSION
Prenatal sonographic detection of echogenic kidneys should raise suspicion for a broad range of disorders, including renal ciliopathies and CAKUT. Multicenter collaboration will be required to standardize the implementation of transition guidelines for comprehensive nephrology management of infants identified with enlarged, echogenic kidneys.
PubMed: 37635794
DOI: 10.3389/fped.2023.1243504 -
BMC Pediatrics Aug 2023Congenital tibial hemimelia (CTH [MIM: 275220]) is a rare congenital limb deficiency that manifests as a shortened, curved, dysplastic or absent tibia with polydactyly....
BACKGROUND
Congenital tibial hemimelia (CTH [MIM: 275220]) is a rare congenital limb deficiency that manifests as a shortened, curved, dysplastic or absent tibia with polydactyly. In previous studies, mutations of a distant sonic hedgehog (SHH) cis-regulator (ZRS) and a Shh repressor (GLI3) were identified.
CASE PRESENTATION
Here, we admitted a 20-month-old boy who manifested with right tibial deformity, varus foot, ankle dislocation, and ipsilateral preaxial polydactyly. After genetic sequencing and data analysis, the results revealed a 443 A > G mutation in the father and a 536 C > T mutation in the mother in exon 2 of the Smoothed (SMO) gene at 7q32.1, with the coexistence of both mutant alleles in the proband/patient.
CONCLUSIONS
Our report suggests that even though not previously reported, SMO mutations may be associated with limb anomalies such as tibial hemimelia via Hh signaling in humans and has implications for genetic counseling.
Topics: Male; Humans; Infant; Hedgehog Proteins; Point Mutation; Tibia; Polydactyly; Smoothened Receptor
PubMed: 37626311
DOI: 10.1186/s12887-023-04167-y -
MedRxiv : the Preprint Server For... Aug 2023Chikungunya virus (CHIKV) has become a global public health concern since the reemergence of the Indian Ocean lineage and expansion of the Asian genotype. CHIKV...
Chikungunya virus (CHIKV) has become a global public health concern since the reemergence of the Indian Ocean lineage and expansion of the Asian genotype. CHIKV infection causes acute febrile illness, rash, and arthralgia and during pregnancy may affect both mothers and infants. The mother-to-child transmission (MTCT) of CHIKV in Africa remains understudied. We screened 1006 pregnant women at two clinics in Nigeria between 2019 and 2022 and investigated the prevalence and MTCT of CHIKV. Of the 1006, 119 tested positive for CHIKV IgM, of which 36 underwent detailed laboratory tests. While none of the IgM reactive samples were RT-PCR positive, 14 symptomatic pregnant women were confirmed by CHIKV neutralization test. Twelve babies were followed with 8 normal and 4 abnormal outcomes, including stillbirth, cleft lip/palate with microcephaly, preterm delivery, polydactyly with sepsis and jaundice. CHIKV IgM testing identified 3 antepartum transmissions, further studies will determine its impact in antepartum infection.
PubMed: 37609297
DOI: 10.1101/2023.08.05.23293675 -
Clinical Medicine Insights. Case Reports 2023Bardet-Biedl syndrome (BBS) also known as Laurence-Moon-Bardet-Biedl syndrome one of the rarely reported genetic disorder characterized by an intellectual disability,...
BACKGROUND
Bardet-Biedl syndrome (BBS) also known as Laurence-Moon-Bardet-Biedl syndrome one of the rarely reported genetic disorder characterized by an intellectual disability, limb, kidney abnormalities, obesity, and Rod-cone dystrophy. Other associated condition includes diabetes mellitus, hypertension, hypogonadism, facial dysmorphism, and congenital heart defects. This case highlights megaloblastic anemia associated with BBS.
CASE PRESENTATION
A 16-year-old female patient who had a moon face, truncal obesity, polydactyly, low IQ, and visual impairment presented with the complaint of shortness of breath and easy fatiguability. She had bilateral retinal pigmentosa in her eyes and her laboratory evaluation and bone marrow biopsy revealed megaloblastic anemia secondary to vitamin B12 deficiency. She received injectable vitamin B12, folate, and red cell contrate transfusion. Her symptoms improved and she was discharged with oral medication.
CONCLUSION
Megaloblastic anemia in BBS is rarely reported, further research is needed to find the exact cause that is necessary for proper management and better outcome.
PubMed: 37588947
DOI: 10.1177/11795476231193896 -
Cureus Jul 2023We report two patients with musculoskeletal manifestations as part of the Bardet-Biedl syndrome. The first patient (case 1) was born with polydactyly and later diagnosed...
We report two patients with musculoskeletal manifestations as part of the Bardet-Biedl syndrome. The first patient (case 1) was born with polydactyly and later diagnosed with coxa vara. He had homozygous pathogenic mutation in the BBS1 gene of the variant c.1645G>T (p.Glu459*). The second patient (case 2) had nyctalopia and progressive vision worsening had osteoarthritis symptoms. He had a heterozygous mutation in the BBS1 gene of the variant c.1169T>G (p.Met390Arg). Although polydactyly is the most prevalent musculoskeletal association in patients with the syndrome, co-management of the musculoskeletal manifestations remains of utmost importance in patients with the syndrome.
PubMed: 37588308
DOI: 10.7759/cureus.41963 -
Cureus Jul 2023Hyperthyroidism is more common in women and the sensitivity of thyroid function changes during pregnancy. Excess levels of thyroid hormones and thioamides have a major... (Review)
Review
Hyperthyroidism is more common in women and the sensitivity of thyroid function changes during pregnancy. Excess levels of thyroid hormones and thioamides have a major impact on maternal and fetal outcomes. Our aim was to perform an extensive literature review and provide relevant details concerning the analytical and clinical aspects of the potential effects of the two main drugs used (methimazole and propylthiouracil) in newborns. A thorough literature review was conducted using PubMed and Google Scholar databases. In total, 10 relevant studies were identified and data from these studies were extracted and then extrapolated into results after analysis. Three out of four studies that used methimazole and carbimazole, one and two, respectively, showed adverse fetal outcomes requiring surgical management for congenital anomalies like aplasia cutis, patent vitellointestinal duct, and gastroschisis. Out of the three studies that used propylthiouracil, one baby underwent surgery for bilateral pyelectasis, vesicovaginal fistula, anal stenosis, and polydactyly. The findings of the aforementioned studies provide enough evidence to imply that the use of methimazole and carbimazole to treat antenatal hyperthyroidism has worse fetal outcomes than the use of propylthiouracil. Also, given the paucity of data in the existing literature regarding propylthiouracil's effects on newborns, further studies in this demographic are needed.
PubMed: 37551246
DOI: 10.7759/cureus.41505 -
Frontiers in Pediatrics 2023Birth defects (BDs) are associated with many potential risk factors, and its causes are complex.
BACKGROUND
Birth defects (BDs) are associated with many potential risk factors, and its causes are complex.
OBJECTIVES
This study aimed to explore the epidemiological characteristics of BDs in Guangxi of China and the associated risk factors of BDs.
METHODS
BDs data of perinatal infants (PIs) were obtained from the Guangxi birth defects monitoring network between 2016 and 2020. Univariate Poisson regression was used to calculate the prevalence-rate ratios (PRR) to explore the changing trends of BDs prevalence by year and the correlation between the regarding of characteristics of BDs (including infant gender, maternal age, and quarter) and BDs. Clinical characteristics of PIs with BDs and general characteristics of their mothers were documented, and Spearman correlation analysis was used to explore the potential associated risk factors of BDs.
RESULTS
Between 2016 and 2020, 44,146 PIs with BDs were monitored, with an overall BDs prevalence of 121.71 (95% CI: 120.58-122.84) per 10,000 PIs, showing a significant increase trend (PRR = 1.116, 95% CI: 1.108-1.123), especially the prevalence of congenital heart defects (CHDs) that most significantly increased (PRR = 1.300, 95% CI: 1.283-1.318). The 10 most common BDs were CHDs, polydactyly, congenital talipes equinovarus, other malformation of external ear, syndactyly, hypospadias, cleft lip with cleft palate, cleft lip, hemoglobin Bart's hydrops fetalis syndrome (BHFS), and congenital atresia of the rectum and anus. BDs were positively correlated with pregnant women's age ( = 0.732, < 0.01) and education level ( = 0.586, < 0.05) and having pre-gestational diabetes mellitus (PGDM)/gestational diabetes mellitus (GDM) ( = 0.711, < 0.01), while when the pregnant women had a family history of a dead fetus ( = -0.536, < 0.05) and a birth of a fetus with BDs ( = -0.528, < 0.05) were negatively correlated with BDs.
CONCLUSION
A significant increase in the prevalence of BDs was detected between 2016 and 2020 in Guangxi, especially the prevalence of CHDs that most significantly increased. Older maternal age, higher maternal education level, and having PGDM before pregnancy or GDM in early pregnancy were the risk factors for BDs.
PubMed: 37547102
DOI: 10.3389/fped.2023.1165477 -
Molecular Genetics & Genomic Medicine Oct 2023Intronic variants outside the canonical splice site are challenging to interpret and therefore likely represent an underreported cause of human disease. Autosomal...
BACKGROUND
Intronic variants outside the canonical splice site are challenging to interpret and therefore likely represent an underreported cause of human disease. Autosomal recessive variants in DYNC2H1 are associated with short-rib thoracic dysplasia 3 with or without polydactyly (SRTD3), a clinically heterogeneous disease generally presenting with short ribs, shortened tubular bones, narrow thorax and acetabular roof anomalies. We describe a case of SRTD3 with compound heterozygous frameshift and intronic variants and highlight the essential role of RNA sequencing (RNA-Seq) in variant interpretation.
METHODS
Following inconclusive clinical genetic testing identifying a likely pathogenic frameshift variant and an intronic variant of uncertain significance (VUS) in DYNC2H1 in trans, the family enrolled in the Care4Rare Canada research program, where RNA-Seq studies were performed.
RESULTS
The proband presented with post-axial polydactyly of all four limbs, a significantly small chest with a pectus excavatum and anterior flaring of the ribs. RNA-Seq investigations revealed a novel splice junction as a result of the intronic VUS and significantly decreased DYNC2H1 gene expression in the proband.
CONCLUSION
This case demonstrates the diagnostic utility of RNA-Seq for variant interpretation following inconclusive clinical testing, which can ultimately lead to diagnosis for patients with rare disease.
PubMed: 37489014
DOI: 10.1002/mgg3.2247 -
Molecular Genetics & Genomic Medicine Oct 2023Pathogenic mutations in EVC or EVC2 gene can lead to Ellis-van Creveld (EvC) syndrome, which is a rare autosomal recessive skeletal dysplasia disorder. This study aimed...
BACKGROUND
Pathogenic mutations in EVC or EVC2 gene can lead to Ellis-van Creveld (EvC) syndrome, which is a rare autosomal recessive skeletal dysplasia disorder. This study aimed to determine pathogenic gene variations associated with EvC syndrome in fetuses showing ultrasound anomalies.
METHODS
A 32-year-old pregnant woman from Quanzhou, China was investigated. In her pregnancy examination, the fetus exhibited multiple fetal malformations, including a narrow thorax, short limbs, postaxial polydactyly, cardiac malformations, and separation of double renal pelvis. Karyotype, chromosomal microarray analysis and whole exome sequencing were performed for prenatal genetic etiology analysis.
RESULTS
Chromosome abnormalities and copy number variants were not observed in the fetus using karyotype and chromosomal microarray analysis. Using whole exome sequencing, two compound heterozygous variants NM_147127.5:c.[2484G>A(p.Trp828Ter)];[871-2_894del] in EVC2 gene were identified in the fetus as pathogenic variants inherited from parents.
CONCLUSIONS
The study is the first to identify two rare compound variants in EVC2 gene in a Chinese family using whole exome sequencing. The application of whole-exome sequencing would be helpful in fetal etiological diagnosis with ultrasound anomalies.
PubMed: 37485807
DOI: 10.1002/mgg3.2242