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American Journal of Medical Genetics.... Jul 2024PRKACA-related, atrial defects-polydactyly-multiple congenital malformation syndrome is a recently described skeletal ciliopathy, which is caused by disease-causing...
PRKACA-related, atrial defects-polydactyly-multiple congenital malformation syndrome is a recently described skeletal ciliopathy, which is caused by disease-causing variants in PRKACA. The primary phenotypic description includes atrial septal defects, and limb anomalies including polydactyly and short limbs. To date, only four molecularly proven patients have been reported in the literature with a recurrent variant, c.409G>A p.Gly137Arg in PRKACA. In this study, we report the fifth affected individual with the same variant and review the clinical features and radiographic findings of this rare syndrome.
Topics: Humans; Polydactyly; Abnormalities, Multiple; Female; Heart Septal Defects, Atrial; Male; Phenotype; Mutation; Heart Defects, Congenital; India
PubMed: 38357848
DOI: 10.1002/ajmg.a.63566 -
Cureus Feb 2024The dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly (DREAM-PL) syndrome is a rare autosomal recessive disorder...
Extensive Phenotypic Variability in Syndrome Dysmorphic Facies, Renal Agenesis, Ambiguous Genitalia, Microcephaly, Polydactyly, and Lissencephaly (DREAM-PL): A Case Report Highlighting Diagnostic and Management Challenges.
The dysmorphic facies, renal agenesis, ambiguous genitalia, microcephaly, polydactyly, and lissencephaly (DREAM-PL) syndrome is a rare autosomal recessive disorder characterized by dysmorphic facies, renal agenesis, ambiguous genitalia in males, microcephaly, polydactyly, and lissencephaly. The CTU2 gene, which encodes a protein involved in the post-transcriptional modification of tRNAs is the source of the syndrome's mutation. Several developmental abnormalities can result from a disruption of this modification, which is necessary for the proper translation of genes. The severity of the symptoms of DREAM-PL syndrome can range from moderate to severe, and its clinical characteristics are quite diverse. Some patients might have some of the distinguishing characteristics, whereas others might have all of them. The most typical characteristics include ambiguous genitalia, dysmorphic facies, and microcephaly. DREAM-PL syndrome is diagnosed based on clinical signs and genetic testing which can show mutations in the CTU2 gene. Although there is no known cure for this syndrome, the treatment aims to manage the symptoms. Other lines of treatment like surgical correction of birth defects can sometimes be beneficial to these patients in addition to supportive care. This study is a report of a 37-week-old male neonate, delivered by lower segment cesarean section. The baby's birth weight is 2.760 kg with a heterozygous confirmed pathogenic mutation of the CTU2 gene confirmed by whole-exome sequencing.
PubMed: 38348206
DOI: 10.7759/cureus.54043 -
Birth Defects Research Feb 2024Polydactyly is a congenital abnormality characterized by the presence of additional fingers on one or more extremities. In Colombia, polydactyly accounted for 17% of...
BACKGROUND
Polydactyly is a congenital abnormality characterized by the presence of additional fingers on one or more extremities. In Colombia, polydactyly accounted for 17% of musculoskeletal congenital abnormalities in 2021, with a prevalence of 6.03 per 10,000 live births. The purpose of this study was to determine the prevalence of polydactyly and identify associated risk factors in Bogotá and Cali, Colombia, from 2002 to 2020.
METHODS
A retrospective case-control study design was employed, analyzing data from birth defect reports provided by the Program for the Prevention and Follow-up of Congenital Defects and Orphan Diseases surveillance system. Cases included live births or stillbirths with polydactyly, while controls consisted of infants without congenital abnormality, matched in terms of birth date and hospital. Prevalence of polydactyly was calculated and risk factors were assessed through odds ratios obtained by logistic regression models, considering a 95% confidence interval.
RESULTS
Among the 558,255 births included in the study, 848 cases of polydactyly were identified, resulting in a prevalence rate of 15.19 per 10,000 live births. Risk factors associated with polydactyly included male newborn sex, pregestational diabetes, and a family history of malformation among first-degree relatives.
CONCLUSION
These findings highlight the importance a surveillance system aimed to characterize populations with congenital abnormalities, providing a better option for analyzing risk factors, help improving prevention, diagnosis, notification, and optimal treatment in patients.
Topics: Infant, Newborn; Humans; Male; Case-Control Studies; Colombia; Retrospective Studies; Polydactyly; Risk Factors
PubMed: 38343155
DOI: 10.1002/bdr2.2312 -
World Journal of Pediatrics : WJP Feb 2024Although birth defects are of great concern globally, the latest national prevalence has not yet been quantified in China. We conducted a systematic review and... (Review)
Review
BACKGROUND
Although birth defects are of great concern globally, the latest national prevalence has not yet been quantified in China. We conducted a systematic review and meta-analysis to estimate the perinatal prevalence of birth defects in the Mainland of China between 2000 and 2021.
METHODS
We performed a systematic literature search of six databases for relevant articles published between January 1, 2000, and March 1, 2023. We included published studies that reported data on the perinatal prevalence of birth defects in the Mainland of China. The DerSimonian and Laird random-effects models were used to estimate the pooled prevalence and its 95% confidence interval (CI). We also conducted subgroup analyses and univariable meta-regressions to explore differences in prevalence by time period, geographic region, and other characteristics.
RESULTS
We included 254 studies reporting the perinatal prevalence of birth defects and 86 studies reporting only the prevalence of specific types of birth defects. Based on 254 studies covering 74,307,037 perinatal births and 985,115 cases with birth defects, the pooled perinatal prevalence of birth defects was 122.54 (95% CI 116.20-128.89) per 10,000 perinatal births in the Mainland of China during 2000-2021. Overall, the perinatal prevalence of birth defects increased from 95.60 (86.51-104.69) per 10,000 in 2000-2004 to 208.94 (175.67-242.22) per 10,000 in 2020-2021. There were also significant disparities among different geographical regions. Congenital heart defects (33.35 per 10,000), clefts of the lip and/or palate (13.52 per 10,000), polydactyly (12.82 per 10,000), neural tube defects (12.82 per 10,000), and inborn errors of metabolism (11.41 per 10,000) were the five most common types of birth defects. The perinatal prevalence among males was significantly higher than that among females (β = 2.44 × 10, P = 0.003); a higher perinatal prevalence of birth defects was observed among perinatal births whose mothers were ≥ 35 years (β = 4.34 × 10, P < 0.001).
CONCLUSION
Comprehensive and sustained efforts are needed to strengthen surveillance and detection of birth defects, improve prenatal and postnatal healthcare, and promote rehabilitation, especially in underdeveloped areas.
PubMed: 38340146
DOI: 10.1007/s12519-023-00786-8 -
Annals of Medicine and Surgery (2012) Feb 2024Bardet-Biedl syndrome (BBS) is a rare autosomal recessive multisystem disorder characterized by retinal dystrophy, obesity, postaxial polydactyly, renal dysfunction,...
INTRODUCTION
Bardet-Biedl syndrome (BBS) is a rare autosomal recessive multisystem disorder characterized by retinal dystrophy, obesity, postaxial polydactyly, renal dysfunction, learning difficulties, and hypogonadism. In this case report, the authors present the clinical course and management of a patient with BBS who developed chronic kidney disease (CKD).
CASE PRESENTATION
An 18-year-old male presented to the emergency department with chief complaints of fever, cough, vomiting, and decreased urine output for 7 days. Parents complained that the child had a delay in development compared to other children of the same age group. On examination, the patient had tachypnea, periorbital and pedal edema, expiratory wheeze with bilateral basal crackles, polydactyly, central obesity, microtestes, and delayed developmental milestones. Ultrasonography revealed bilateral small kidneys with increased cortical echotexture and loss of corticomedullary differentiation. Based on clinical features, the patient was diagnosed with CKD in the background of BBS. Hemodialysis was initiated after the diagnosis.
DISCUSSION
The management of CKD in the background of BBS poses unique challenges due to the complex multisystem involvement of this genetic disorder. There should be early reorganization and management of this condition so that the patient can have a better quality of life. Moreover, in developing countries like Nepal, genetic testing and diagnosis should be made easily accessible for better patient outcome.
CONCLUSION
Multidisciplinary approach involving nephrologists, ophthalmologists, endocrinologists, and geneticists is important to optimize the treatment and long-term management of Badet Biedel patients.
PubMed: 38333249
DOI: 10.1097/MS9.0000000000001626 -
Clinical, Cosmetic and Investigational... 2024Acquired digital fibrokeratoma (ADF) is rare in clinical practice and is easily misdiagnosed. Herein, 5 cases of patients (3 males and 2 females) with ADF are reported....
Acquired digital fibrokeratoma (ADF) is rare in clinical practice and is easily misdiagnosed. Herein, 5 cases of patients (3 males and 2 females) with ADF are reported. The mean age at onset was 42.6 years, and the mean disease duration was 3 years. Four patients had ADF on the hands, and 1 patient had ADF on the foot. The clinical manifestations were all solitary, skin-colored papules, with a firm texture and smooth surface, protruding from the skin surface. In 3 patients, ADF manifested as columnar protrusions, and in 2 patients, ADF manifested as dome-shaped protrusions. For all 5 patients, the diameters of the lesions were <1 cm. Clinically, all 5 patients were misdiagnosed (ie, eccrine poroma (EP), common warts, rudimentary polydactyly, pyogenic granuloma (PG), and acral fibroma). All cases of ADF were confirmed by histopathology. The histopathological manifestations of ADF were as follows: finger-like protrusions on the skin surface; collagen fiber bundles running vertically to the epidermis seen in the dermis; and thick red-stained collagen fibers connected with the normal dermal connective tissue below. All 5 patients underwent surgical resection; the distance between the incision margin and the edge of the tumor was 2-3 mm, and the surgical depth was the deep dermis. No recurrence was observed in more than half a year of follow-up after surgery.
PubMed: 38314146
DOI: 10.2147/CCID.S447798 -
Zhonghua Yi Xue Yi Chuan Xue Za Zhi =... Feb 2024To carry out prenatal diagnosis for a fetus with Meckel syndrome (MKS) and explore its genetic basis.
OBJECTIVE
To carry out prenatal diagnosis for a fetus with Meckel syndrome (MKS) and explore its genetic basis.
METHODS
A pregnant woman presented at Suzhou Municipal Hospital in February 2018 was selected as the study subject. Clinical data was collected. Muscle tissue sample from the abortus and peripheral blood samples from the couple were collected. Genomic DNA was extracted and subjected to chromosomal microarray analysis (CMA) and whole exome sequencing. Candidate variant was verified by Sanger sequencing.
RESULTS
The fetus was found to have microcephaly, oligohydramnios, polycystic kidneys and banana-shaped cerebellum at 18 weeks of gestation. After induction of labor, it was found to have encephalocele, renal cysts and polydactyly. CMA has found no abnormality. Whole exome sequencing revealed novel compound heterozygous variants c.296delA (p.Lys99SerfsTer6) and c.1243G>A (p.Val415Met) in the TMEM67 gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c.296delA variant was predicted to be pathogenic (PVS1+PM2_Supporting+PP4), whilst the c.1243G>A variant was predicted to be likely pathogenic (PM2_Supporting+PM3+PP3_Moderate+PP4).
CONCLUSION
The c.296delA and c.1243G>A compound heterozygous variants of the TMEM67 gene probably underlay the MKS in this fetus.
Topics: Female; Pregnancy; Humans; Encephalocele; Polycystic Kidney Diseases; Fetus; Ciliary Motility Disorders; Mutation; Membrane Proteins; Retinitis Pigmentosa
PubMed: 38311563
DOI: 10.3760/cma.j.cn511374-20230201-00045 -
Diabetes, Obesity & Metabolism Apr 2024Bardet-Biedl syndrome (BBS) is a rare, monogenic, multisystem disorder characterized by retinal dystrophy, renal abnormalities, polydactyly, learning disabilities, as... (Review)
Review
Bardet-Biedl syndrome (BBS) is a rare, monogenic, multisystem disorder characterized by retinal dystrophy, renal abnormalities, polydactyly, learning disabilities, as well as metabolic dysfunction, including obesity and an increased risk of type 2 diabetes. It is a primary ciliopathy, and causative mutations in more than 25 different genes have been described. Multiple cellular mechanisms contribute to the development of the metabolic phenotype associated with BBS, including hyperphagia as a consequence of altered hypothalamic appetite signalling as well as alterations in adipocyte biology promoting adipocyte proliferation and adipogenesis. Within this review, we describe in detail the metabolic phenotype associated with BBS and discuss the mechanisms that drive its evolution. In addition, we review current approaches to the metabolic management of patients with BBS, including the use of weight loss medications and bariatric surgery. Finally, we evaluate the potential of targeting hypothalamic appetite signalling to limit hyperphagia and induce clinically significant weight loss.
Topics: Humans; Bardet-Biedl Syndrome; Diabetes Mellitus, Type 2; Kidney; Hyperphagia; Weight Loss
PubMed: 38302651
DOI: 10.1111/dom.15480 -
JPRAS Open Mar 2024Congenital thumb duplication is estimated to occur between 0.08 and 7.6 times per 1,000 live births; however its cause is still undetermined. In this report, we present...
Congenital thumb duplication is estimated to occur between 0.08 and 7.6 times per 1,000 live births; however its cause is still undetermined. In this report, we present a case of Wassel type VI thumb polydactyly. clinical examination revealed an optimal functional position and an aesthetically pleasing shape of the ulnar thumb as well as a superior nail and pulp. However, preoperative X-ray indicated a well formed carpometacarpal joint of the radial thumb compared to an underdeveloped CMC joint of the ulnar thumb. Through surgical procedure we combined the best parts of both thumbs with on-top plasty to achieve the most optimal outcome. In conclusion, it is important to determine an adequate treatment strategy for a patient based on both clinical and radiological assessments.
PubMed: 38293284
DOI: 10.1016/j.jpra.2023.12.007