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Case Reports in Ophthalmological... 2023A rare multisystemic, ciliopathic autosomal recessive disorder called Bardet-Biedl syndrome (BBS) primarily affects children of consanguineous marriages. Both men and...
A rare multisystemic, ciliopathic autosomal recessive disorder called Bardet-Biedl syndrome (BBS) primarily affects children of consanguineous marriages. Both men and women are affected by it. It is characterized by some major and many minor features to aid in the clinical diagnosis and management. Here, we reported two Bangladeshi patients (a 9-year-old girl and 24-year-old male) who were presented with various major and minor features of BBS. Both patients came to us with the symptoms including excessive weight gain, poor vision, and learning disabilities with polydactyly. Our case 1 presented four primary features (retinal degenerations, polydactyly, obesity, and learning deficits) and six secondary features (behavioral abnormality, delayed development, diabetes mellitus, diabetes insipidus, brachydactyly, and LVH), whereas case 2 presented five major criteria (truncal obesity, polydactyly, retinal dystrophy, learning disabilities, and hypogonadism) and six minor criteria (strabismus and cataract, delay in speech, behavioral disorder, developmental delay, brachydactyly and syndactyly, and impaired glucose tolerance test). We diagnosed the cases as BBS. Because there is no specific treatment for BBS, we highlighted the importance of diagnosing it as early as possible so that comprehensive and multidisciplinary care can be offered to prevent avoidable morbidity and mortality.
PubMed: 37096247
DOI: 10.1155/2023/4017010 -
Molecular Syndromology Feb 2020We report a family with a spectrum of short stature, craniofacial dysmorphism, and digital anomalies in a father and 2 daughters, with the youngest (proband) displaying...
We report a family with a spectrum of short stature, craniofacial dysmorphism, and digital anomalies in a father and 2 daughters, with the youngest (proband) displaying a severe phenotype. Clinically, autosomal dominant Robinow syndrome (ADRS) was diagnosed. Whole-exome sequencing identified a heterozygous pathogenic variant in the father and his daughters. The phenotype of short stature, facial dysmorphism, and skeletal anomalies with or without cardiac anomalies related to haploinsufficiency has some facial and digital resemblance to ADRS. Although this variant segregated in the affected members, it failed to explain the severe phenotype of the proband. A reanalysis of the girl's raw data confirmed 2 disorders: a de novo likely pathogenic variant implicated in ADRS and the familial variant. A close interplay of high-throughput sequencing and deep phenotyping unraveled the complexities of the blended phenotype in the proband.
PubMed: 32256301
DOI: 10.1159/000505506 -
International Journal of Ophthalmology 2023To explore the phenotype and genotype of Weill-Marchesani syndrome (WMS) in a Chinese family and review related literature.
AIM
To explore the phenotype and genotype of Weill-Marchesani syndrome (WMS) in a Chinese family and review related literature.
METHODS
Three WMS patients and other unaffected individuals in this family with a history of consanguineous marriage were included in this study. Medical history, comprehensive ophthalmic examinations, and systemic evaluation, as well as whole exome and Sanger sequencing of specific genomic regions, were performed.
RESULTS
The three affected siblings presented with short stature, brachydactyly and ocular disorders, including very shallow anterior chamber, high myopia, microspherophakia lens subluxation with stretched zonules and glaucoma. Genetic analysis verified a homozygous missense mutation (c.2983C>T: p. Arg995Trp) in , which was correlated with the diseases in this family, indicating an autosomal recessive inherited manner of WMS. This review aims to summarize the mutation sites of WMS genes, so as to prevent the disease and better guide clinical diagnosis and treatment.
CONCLUSION
A novel homozygous missense variant of is identified in a WMS family with a history of consanguineous marriage. Our study expands the range of mutations associated with WMS and deepens our understanding of pathology in disease associated with variants.
PubMed: 37206179
DOI: 10.18240/ijo.2023.05.04 -
Acta Medica Indonesiana Jan 2022Ciliopathy syndrome is a congenital abnormality of structure and/or function of cilia, which causes pleiotropic disorder, including liver cirrhosis. This study aimed to...
Ciliopathy syndrome is a congenital abnormality of structure and/or function of cilia, which causes pleiotropic disorder, including liver cirrhosis. This study aimed to describe a unique case of liver cirrhosis with possible aetiology of ciliopathy syndrome. A 44 year-old woman with chief complain of hematemesis had diabetes mellitus, obesity, dyslipidaemia, amenorrhoea and often became unconscious. We found short stature, brachydactyly, hyperpigmented maculae in trunk and four limbs, and hepatosplenomegaly. The laboratory results showed: haemoglobin 7.4 g/dl; albumin 2.42 g/dl; urea 84.8 mg/dl; creatinine 2.4 mg/dl; prolactin 138.8 ng/ml, while HBsAg was negative and anti-HCV was non-reactive. Abdominal ultrasonography showed liver cirrhosis; endoscopy showed grade 3 oesophageal varicose; FibroScanī showed 75 kPa; liver biopsy showed hydropic degeneration and cirrhosis; and head CT scan showed chronic lacunar infarction of corona radiata and mega cisterna magna occipital. We reported female with oesophageal varicose rupture, short stature, brachydactyly, obesity, diabetes mellitus, dyslipidaemia, hyperpigmented maculae, liver cirrhosis and mega cisterna magna, which was likely to suffer from ciliopathy syndrome.
Topics: Adult; Brachydactyly; Ciliopathies; Esophageal and Gastric Varices; Female; Humans; Liver; Liver Cirrhosis; Obesity
PubMed: 35398832
DOI: No ID Found -
Genetics in Medicine : Official Journal... Jan 2023Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyzes the methylation of arginine residues on several protein substrates....
Biallelic PRMT7 pathogenic variants are associated with a recognizable syndromic neurodevelopmental disorder with short stature, obesity, and craniofacial and digital abnormalities.
PURPOSE
Protein arginine methyltransferase 7 (PRMT7) is a member of a family of enzymes that catalyzes the methylation of arginine residues on several protein substrates. Biallelic pathogenic PRMT7 variants have previously been associated with a syndromic neurodevelopmental disorder characterized by short stature, brachydactyly, intellectual developmental disability, and seizures. To our knowledge, no comprehensive study describes the detailed clinical characteristics of this syndrome. Thus, we aim to delineate the phenotypic spectrum of PRMT7-related disorder.
METHODS
We assembled a cohort of 51 affected individuals from 39 different families, gathering clinical information from 36 newly described affected individuals and reviewing data of 15 individuals from the literature.
RESULTS
The main clinical characteristics of the PRMT7-related syndrome are short stature, mild to severe developmental delay/intellectual disability, hypotonia, brachydactyly, and distinct facial morphology, including bifrontal narrowing, prominent supraorbital ridges, sparse eyebrows, short nose with full/broad nasal tip, thin upper lip, full and everted lower lip, and a prominent or squared-off jaw. Additional variable findings include seizures, obesity, nonspecific magnetic resonance imaging abnormalities, eye abnormalities (i.e., strabismus or nystagmus), and hearing loss.
CONCLUSION
This study further delineates and expands the molecular, phenotypic spectrum and natural history of PRMT7-related syndrome characterized by a neurodevelopmental disorder with skeletal, growth, and endocrine abnormalities.
Topics: Humans; Brachydactyly; Neurodevelopmental Disorders; Intellectual Disability; Dwarfism; Musculoskeletal Abnormalities; Obesity; Phenotype; Protein-Arginine N-Methyltransferases
PubMed: 36399134
DOI: 10.1016/j.gim.2022.09.016 -
BioMed Research International 2020Synpolydactyly type 1 (SPD1, OMIM 186000) is inherited as autosomal dominant and is caused by mutations. The condition is rare and is known for its phenotypic... (Review)
Review
A Review of the Phenotype of Synpolydactyly Type 1 in Homozygous Patients: Defining the Relatively Long and Medially Deviated Big Toe with/without Cupping of the Forefoot as a Pathognomonic Feature in the Phenotype.
Synpolydactyly type 1 (SPD1, OMIM 186000) is inherited as autosomal dominant and is caused by mutations. The condition is rare and is known for its phenotypic heterogeneity. In the homozygous state, the phenotype is generally more severe and is characterized by three main features: a more severe degree of syndactyly, a more severe degree of brachydactyly, and the frequent loss of the normal tubular shape of the metacarpals/metatarsals. Due to the phenotypic heterogeneity and the phenotypic overlap with other types of syndactyly, no pathognomonic feature has been described for the homozygous phenotype of SPD1. In the current communication, the author reviews the literature on the phenotypes of SPD1 in homozygous patients. The review documents that not all homozygous patients show a severe hand phenotype. The review also defines the "relatively long and medially deviated big toe with/without cupping of the forefoot" as a pathognomonic feature in the phenotype. Illustration of this feature is done through a demonstrative clinical report in a multigeneration family with SPD1 and polyalanine repeat expansion. Finally, the pathogenesis of the clinical features is reviewed.
Topics: Adult; Child; Female; Foot; Hallux; Hand; Homeodomain Proteins; Homozygote; Humans; Male; Mutation; Phenotype; Syndactyly; Transcription Factors
PubMed: 32509852
DOI: 10.1155/2020/2067186 -
Journal of Oral Biology and... 2021Pycnodysostosis is a rare autosomal recessive condition caused by the mutation of CTSK gene. CTSK regulates the activity of Cathepsin K which is responsible for...
Pycnodysostosis is a rare autosomal recessive condition caused by the mutation of CTSK gene. CTSK regulates the activity of Cathepsin K which is responsible for osteoclast-mediated bone resorption. This mutation causes the bones to become dense, sclerotic, brittle, and thus, prone to fracture. Affected individuals have normal cognitive development and life expectancy, however, the quality of life depends on the early diagnosis of the condition. The patient presents with striking clinical (short stature, brachydactyly) and radiological (frontal and parieto-occipital bossing, open sutures, and fontanelles, acro-osteolysis of terminal phalanges) features making the diagnosis clinico-radiographic. In atypical or mild cases with overlapping features, gene mapping is advocated. A plethora of dental anomalies and characteristic craniofacial dysmorphia puts the dentist in a position to diagnose such a case.
PubMed: 34377661
DOI: 10.1016/j.jobcr.2021.07.006 -
Clinical Pediatric Endocrinology : Case... 2023Brachydactyly mental retardation syndrome (BDMR) or chromosome 2q37 deletion syndrome is a genetic disorder caused by 2q37 deletion or haploinsufficiency of histone...
Brachydactyly mental retardation syndrome (BDMR) or chromosome 2q37 deletion syndrome is a genetic disorder caused by 2q37 deletion or haploinsufficiency of histone deacetylase 4 (HDAC4). The gene is responsible for major BDMR phenotypes. The symptoms of BDMR include mild-to-moderate intellectual disability, seizures, autism spectrum disorder, short stature, obesity, and facial dysmorphism. Here, we report a family (n = 5) with BDMR who had a missense variant of . Four affected individuals [5-yr-old girl (index case); 15- and 3-yr-old siblings; and father] had mild intellectual disability, three of the four affected individuals had short stature and mild cardiac anomalies, and two of the four affected individuals had hypothyroidism. Whole-exome sequencing and analyses of the index case and her family revealed an allelic variant in the gene (NM_001378414.1:c.2204G>A:p. Arg735Gln). A healthy family member (mother) did not have the missense variant. To our knowledge, this is the first report of a missense variation in that is associated with BDMR.
PubMed: 37020696
DOI: 10.1297/cpe.2022-0076 -
Journal of Pediatric Neurosciences 2019Peter plus syndrome (PPS) is a rare, hereditary (autosomal recessive) disorder characterized by a mutation in the beta-1,3-galactosyltransferase-like gene (chromosome...
Peter plus syndrome (PPS) is a rare, hereditary (autosomal recessive) disorder characterized by a mutation in the beta-1,3-galactosyltransferase-like gene (chromosome 13q12), which causes impaired glycosylation of several structural and functional proteins throughout the body. Clinical signs and symptoms of PPS are highly variable and include structural malformations affecting multiple organ systems including central nervous system. We aim to discuss a neurosurgeon's perspective to PPS in this report. A 2-year-old boy presented with congenital dysmorphic facies, bilateral central corneal opacities, delayed developmental milestones, short-stature (75cm), rhizomelia with brachydactyly, and history of surgery for anal atresia on the second day of life. Screening craniospinal magnetic resonance imaging revealed mild ventriculomegaly, cavum septum pellucidum, cavum velum interpositum, vermian hypoplasia, and normal spine. Cytogenetic analysis showed a mutation in the beta-1,3-galactosyltransferase-like gene on chromosome 13. Clinical picture in our patient suggested the diagnosis of PPS. Parents often seek ophthalmological consultation due to visual impairment predominantly, and this syndrome largely remains unknown among neurosurgeons. Nonetheless, babies with PPS may present with neurological symptoms such as seizures, spastic diplegia, tinnitus, or hearing loss as well as a life-threatening neurosurgical emergency arising due to raised intracranial pressure. Therefore, the role of neurosurgeon becomes crucial in managing these cases.
PubMed: 31649776
DOI: 10.4103/jpn.JPN_33_19 -
BMC Pediatrics Sep 2022Brachydactyly type B is an autosomal dominant disorder that is characterized by hypoplasia of the distal phalanges and nails and can be divided into brachydactyly type...
BACKGROUND
Brachydactyly type B is an autosomal dominant disorder that is characterized by hypoplasia of the distal phalanges and nails and can be divided into brachydactyly type B1 (BDB1) and brachydactyly type B2 (BDB2). BDB1 is the most severe form of brachydactyly and is caused by truncating variants in the receptor tyrosine kinase-like orphan receptor 2 (ROR2) gene.
CASE PRESENTATION
Here, we report a five-generation Chinese family with brachydactyly with or without syndactyly. The proband and her mother underwent digital separation in syndactyly, and the genetic analyses of the proband and her parents were provided. The novel heterozygous frameshift variant c.1320dupG, p.(Arg441Alafs*18) in the ROR2 gene was identified in the affected individuals by whole-exome sequencing and Sanger sequencing. The c.1320dupG variant in ROR2 is predicted to produce a truncated protein that lacks tyrosine kinase and serine/threonine- and proline-rich structures and remarkably alters the tertiary structures of the mutant ROR2 protein.
CONCLUSION
The c.1320dupG, p.(Arg441Alafs*18) variant in the ROR2 gene has not been reported in any databases thus far and therefore is novel. Our study extends the gene variant spectrum of brachydactyly and may provide information for the genetic counselling of family members.
Topics: Brachydactyly; Carpal Bones; Female; Foot Deformities, Congenital; Hand Deformities, Congenital; Humans; Pedigree; Receptor Tyrosine Kinase-like Orphan Receptors; Stapes; Syndactyly; Synostosis; Tarsal Bones
PubMed: 36064339
DOI: 10.1186/s12887-022-03564-z