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International Journal of Infectious... Feb 2024Chikungunya virus (CHIKV), a reemerging global public health concern, which causes acute febrile illness, rash, and arthralgia and may affect both mothers and infants...
OBJECTIVES
Chikungunya virus (CHIKV), a reemerging global public health concern, which causes acute febrile illness, rash, and arthralgia and may affect both mothers and infants during pregnancy. Mother-to-child transmission (MTCT) of CHIKV in Africa remains understudied.
METHODS
Our cohort study screened 1006 pregnant women with a Zika/dengue/CHIKV rapid test at two clinics in Nigeria between 2019 and 2022. Women who tested positive for the rapid test were followed through their pregnancy and their infants were observed for 6 months, with a subset tested by reverse transcription-polymerase chain reaction (RT-PCR) and neutralization, to investigate seropositivity rates and MTCT of CHIKV.
RESULTS
Of the 1006, 119 tested positive for CHIKV immunoglobulin (Ig)M, 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 eight normal and four abnormal outcomes, including stillbirth, cleft lip/palate with microcephaly, preterm delivery, polydactyly with sepsis, and jaundice. CHIKV IgM testing identified three possible antepartum transmissions.
CONCLUSION
In Nigeria, we found significant CHIKV infection in pregnancy and possible CHIKV antepartum transmission associated with birth abnormalities.
Topics: Infant; Infant, Newborn; Humans; Female; Pregnancy; Chikungunya virus; Pregnant Women; Cohort Studies; Nigeria; Cleft Lip; Infectious Disease Transmission, Vertical; Cleft Palate; Chikungunya Fever; Zika Virus Infection; Zika Virus; Stillbirth; Immunoglobulin M; Dengue
PubMed: 38056689
DOI: 10.1016/j.ijid.2023.11.036 -
Frontiers in Genetics 2023To analyze the phenotypes, genotypes, and the relationship of phenotypes and genotypes for Chinese patients with Bardet-Biedl syndrome (BBS). The Chinese Wanfang and...
To analyze the phenotypes, genotypes, and the relationship of phenotypes and genotypes for Chinese patients with Bardet-Biedl syndrome (BBS). The Chinese Wanfang and Weipu data, and PubMed were searched up to December 2022. Patients with detailed clinical feature data were involved in the analysis. A total of 153 Chinese patients, including 87 males, 53 females, and 12 unknown, were enrolled. Their ages ranged from 1.2 to 44 years old with a mean of 16.70 ± 9.90 years old. Among these patients, 80 (52.29%) were reported by ophthalmologists, and only 24 (15.68%) reported by pediatricians. Most patients (132/137, 96.35%) had visual problems; 131/153 (85.62%) had polydactyly; 124/132 (93.93%) were overweight or obese; 63/114 (55.26%) had renal abnormalities; kidney dysfunction was found in 33 (21.57%); 83/104 (79.81%) had hypogonadism and/or genital hypoplasia; and 111/136 (81.62%) had mental retardation. In this series, genetic analysis was performed in 90 (58.82%) patients, including 22 (24.71%), 20 (22.73%), and 10 (11.24%) patients. Moreover, 11 fetuses were diagnosed prenatally in the last 4 years except for one patient in 2004 year. It was noted that had higher penetrance. had higher hearing impairment and lower renal abnormality penetrance. also had lower renal abnormality penetrance as well. Misdiagnosis or miss diagnosis of BBS may be common in China. In patients with polydactyly, visual impairment, obesity, renal abnormalities, hypogonadism, and mental retardation, or in fetuses with polydactyly and/or renal abnormalities, BBS should be considered in the differential diagnosis. Other deformities should be evaluated carefully and genetic analysis should be performed as early as possible.
PubMed: 38034494
DOI: 10.3389/fgene.2023.1247557 -
Cureus Nov 2023The term "delta phalanx" is proposed to characterize an uncommon deformity that typically affects the middle phalanx of a finger. It has the appearance of the Greek...
The term "delta phalanx" is proposed to characterize an uncommon deformity that typically affects the middle phalanx of a finger. It has the appearance of the Greek capital letter delta, meaning it is shaped like a triangle. Because the faulty epiphysis occurs proximally to distally instead of along its usual horizontal course, the bone has a semilunar shape. Functional impairment or significant finger shortening are indications for surgery. A variety of congenital hand anomalies are linked to the delta phalanx. Few cases of middle delta phalanx in the ulnar polydactyly finger have been documented. This case study investigates an extremely uncommon occurrence of metacarpal delta phalanx in an ulnar polydactyly finger.
PubMed: 38024053
DOI: 10.7759/cureus.49484 -
Cureus Oct 2023Laurence-Moon-Bardet Biedl syndrome (LMBBS) is a rare autosomal recessive genetic disorder that is most frequently found in children born from consanguineous marriages....
Laurence-Moon-Bardet Biedl syndrome (LMBBS) is a rare autosomal recessive genetic disorder that is most frequently found in children born from consanguineous marriages. The most prominent clinical characteristics of this syndrome include rod and cone dystrophy, nystagmus, central obesity, polydactyly, hypogonadism in males, renal anomalies, developmental delay, ataxia, speech difficulties, and poor coordination. In this report, we describe the case of a 31-year-old male who had the classical clinical features of LMBBS like developmental delay, retinitis pigmentosa, nystagmus, obesity, hypogonadism, and central obesity, presenting with abdominal pain associated with vomiting and tenderness in the right lower quadrant. The patient was diagnosed with cholelithiasis. This case report emphasizes the atypical complication of cholelithiasis due to the underlying syndrome and the need for further research in this area.
PubMed: 38021809
DOI: 10.7759/cureus.47316 -
Medicine Nov 2023Joubert syndrome is a rare disease of genetic origin with autosomal recessive inheritance and extreme genetic heterogeneity with more than 40 causative genes. Joubert...
INTRODUCTION
Joubert syndrome is a rare disease of genetic origin with autosomal recessive inheritance and extreme genetic heterogeneity with more than 40 causative genes. Joubert syndrome 7 is caused by mutations in the RPGRIP1L gene.
PATIENT CONCERNS
Our report describes a pediatric patient with clinical features compatible with JS type 7 such as hypotonia, developmental delay and aplasia of the cerebellar vermis.
DIAGNOSIS
The clinical features and the MRI of the head and neck which showed alterations at the level of the posterior fossa, with absence of the vermis and horizontal disposition of the cerebellar peduncles, were compatible with Joubert syndrome. Whole exome sequencing detected the variants RPGRIP1L (NM_015272.2) c.697A > T (p. Lys233Ter) and RPGRIP1L (NM_015272.2) c.3545 del (p.Pro1182LeufsTer25).
INTERVENTIONS
Resection was performed to correct the polydactyly. At age 2 years umbilical hernia, adenoid surgery and ventilatory tubes surgery were performed. Renal biopsy confirmed interstitial fibrosis and focally accentuated mild tubular atrophy with focal tubular hypertrophy, compatible with the clinical suspicion of Joubert syndrome. Congenital hip dislocation surgery was performed. The patient underwent surgery for correction of concomitant divergent strabismus and continued with glasses for astigmatism and hyperopia.
OUTCOMES
Sanger sequencing confirmed the patient´s results and the father was found to be a carrier of RPGRIP1L (NM_015272.2) c.697A > T (p. Lys233Ter) and the mother and maternal grandmother as carriers of RPGRIP1L (NM_015272.2) c.3545del (p.Pro1182LeufsTer25). RPGRIP1L:c.3545del novel variant is a deletion which changes the reading frame, altering the RPGR1_C terminal domain and giving rise to an incomplete protein whose functions will be altered.
CONCLUSION
This is the first genetically confirmed case of JS in Colombia, the first carrier of biallelic RPGRIP1L gene mutations with hip dislocation and incomplete glottic closure and the first report of the novel c.3545del likely pathogenic variant causing JS.
Topics: Child, Preschool; Humans; Abnormalities, Multiple; Adaptor Proteins, Signal Transducing; Cerebellum; Eye Abnormalities; Kidney Diseases; Kidney Diseases, Cystic; Mutation; Retina
PubMed: 38013309
DOI: 10.1097/MD.0000000000035600 -
A diagnostic conundrum in Bardet-Biedl syndrome: when genetic diagnosis precedes clinical diagnosis.Endocrinology, Diabetes & Metabolism... Oct 2023Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive, multisystem non-motile ciliopathy of progressive onset. It is primarily characterised by rod-cone dystrophy,...
SUMMARY
Bardet-Biedl syndrome (BBS) is a rare, autosomal recessive, multisystem non-motile ciliopathy of progressive onset. It is primarily characterised by rod-cone dystrophy, early-onset obesity and related complications, postaxial polydactyly, renal and genitourinary abnormalities, learning disabilities, and hypogonadism. The diagnosis is based on Beales' modified diagnostic criteria. We present a case of two monozygotic female twins, 17 years of age at presentation, referred for obesity since childhood. The initial hormonal work-up was negative and no dysmorphic features were noted. They were diagnosed with exogenous obesity. However, after ophthalmologic problems became apparent, rod-cone dystrophy was observed and genetic testing was performed. A mutation in the BBS2 gene led to the diagnosis of BBS, although the full diagnostic criteria were not met. This case not only highlights the need to raise awareness for BBS but also exposes two limitations of the current diagnostic standard. The first limitation is the low sensitivity of the clinical diagnostic model, due to the progressive onset and the high variability of the syndrome. The second limitation is the unclear role of genetic testing. As genetic testing becomes more widely available, genetic diagnosis preceding clinical diagnosis will become more common, leading to a diagnostic conundrum. We propose an update of the diagnostic model. A less strict application in the presence of confirmed genetic mutations should be applied, as this could facilitate earlier diagnosis and intervention. This is important because therapeutic agents are being developed that could have a significant impact on quality of life and prognosis.
LEARNING POINTS
Due to the low prevalence, the significant inter-and intrafamilial variation, and the slowly evolving phenotype, monogenic forms of obesity such as Bardet-Biedl syndrome are difficult to diagnose. Despite advances in the understanding of the presentation, pathophysiology and access to accurate genetic characterisation, a substantial number of diagnoses are still made by ophthalmology, as recognition of BBS in other departments of medicine, remains limited. Clinical diagnosis of BBS is based on Beales' modified diagnostic criteria which require the presence of four primary features or three primary features plus two secondary features. This model has its limitations. Due to the progressive onset of clinical symptoms, patients generally do not meet the diagnostic criteria early in life, leading to a delay in diagnosis. In addition, the role of genetic testing remains controversial. However, as it becomes more widely available, genetic diagnosis may precede a full clinical diagnosis. BBS has an impact on the quality of life and prognosis of both the patient and the family. Obesity management strategies are an important part of the multidisciplinary approach, as there is no cure available. Setmelanotide has shown promising results in a phase 3 trial, but its effect in clinical practice remains unproven.
PubMed: 37997784
DOI: 10.1530/EDM-23-0055 -
The Journal of Foot and Ankle Surgery :... 2024Little is known about functional outcomes in children with treated lower extremity polydactyly (LEP). No classification system has been shown to be prognostically useful...
Little is known about functional outcomes in children with treated lower extremity polydactyly (LEP). No classification system has been shown to be prognostically useful for functional outcomes. This study investigates whether children with treated LEP learn to walk at an age comparable to the population and whether the SAM (severity of syndactyly, axis deviation and metatarsal involvement) classification system is prognostically useful. In a retrospective cohort of 18 patients, we tested for associations between patient characteristics and SAM scores, age at learning to walk, and ability to fit off-the-shelf shoes. The proportion of children with treated LEP able to walk at 18 months of age was compared with the general population. We found no association between the age at which the 17 participants learned to walk and the severity of syndactyly (p = .214), axis deviation (p = .723) and metatarsal involvement (p = .781), nor between the proportion of patients able to wear off-the-shelf shoes compared to those requiring extra wide off-the-shelf shoes and the severity of syndactyly (p = 1.000), axis deviation (p = 1.000) and metatarsal involvement (p = 1.000). We found a trend between older age at surgery and the need for extra wide off-the-shelf shoes (OR = 1.008, p = .080). We found no significant difference in the proportion of children able to walk at 18 months between our patients (proportion = 1.00) and the general population (proportion = 0.95) (p = 1.000). We found no significant association between different SAM scores and functional outcomes, and none in the proportion of children able to walk at 18 months between treated LEP patients and the general population.
Topics: Child; Humans; Toes; Retrospective Studies; Foot; Polydactyly; Syndactyly
PubMed: 37951458
DOI: 10.1053/j.jfas.2023.11.004 -
The Journal of Craniofacial SurgeryBlepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a relatively uncommon autosomal-dominant genetic disorder, primarily attributed to mutations in the...
Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a relatively uncommon autosomal-dominant genetic disorder, primarily attributed to mutations in the forkhead box L2 (FOXL2) gene. Albeit the involvement of protein-coding regions of FOXL2 has been observed in the majority of BPES cases, whether deficiencies in regulatory elements lead to the pathogenesis remains poorly understood. Herein, an autosomal-dominant BPES type II family was included. Peripheral venous blood has been collected, and genomic DNA has been extracted from leukocytes. A whole exome sequencing analysis has been performed and analyzed (Deposited in NODE database: OER422653). The promoter region of FOXL2 was amplified using polymerase chain reaction (PCR). The luciferase reporter assay was performed to identify the activity of this region. In this study, we present a Chinese family diagnosed with type II BPES, characterized by the presence of small palpebral fissures, ptosis, telecanthus, and epicanthus inversus. Notably, all male individuals within the family display polydactyly. A 225-bp deletion in the 556-bp 5'-upstream to transcription start site of FOXL2 , decorated by multiple histone modifications, was identified in affected members of the family. This deletion significantly decreased FOXL2 promoter activity, as measured by the luciferase assay. Conclusively, a novel 255-bp-deletion of the FOXL2 promoter was identified in Chinese families with BPES. Our results expand the spectrum of known FOXL2 mutations and provide additional insight into the genotype-phenotype relationships of the BPES pathogenesis. In addition, this study indicates the important role of genetic screening of cis-regulatory elements in testing heritable diseases.
Topics: Humans; Male; Forkhead Box Protein L2; Blepharophimosis; Pedigree; Blepharoptosis; Mutation; Promoter Regions, Genetic; China; Luciferases; Skin Abnormalities; Urogenital Abnormalities
PubMed: 37938073
DOI: 10.1097/SCS.0000000000009801