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Archivos Argentinos de Pediatria Dec 2018Supernumerary teeth represent a common human dental anomaly, defined as presence of extra teeth-more than the normal number foreseen in primary or permanent dentition.... (Review)
Review
Supernumerary teeth represent a common human dental anomaly, defined as presence of extra teeth-more than the normal number foreseen in primary or permanent dentition. The prevalence has been reported between 0.2 to 3%, and is more frequent in males than females. The etiology is heterogeneous, highly variable and most of the cases are idiopathic. However, the presence of multiple impacted or erupted supernumerary teeth is rare and associated with some genetic syndromes: cleidocranial displasia, familial adenomatous polyposis, trichorhinophalangeal syndrome type I, Rubinstein-Taybi syndrome, Nance-Horan syndrome, Opitz G/BBB syndrome, oculofaciocardiodental syndrome and Robinow syndrome (autosomal dominant). The supernumerary teeth should be considered in order to possibly diagnose these entities with the aim of offering an interdisciplinary management and treatment, as well as offer adequate family genetic counseling.
Topics: Female; Genetic Counseling; Humans; Male; Prevalence; Syndrome; Tooth, Impacted; Tooth, Supernumerary
PubMed: 30457727
DOI: 10.5546/aap.2018.eng.437 -
Journal of Medical Genetics May 2002In 1969, Robinow and colleagues described a syndrome of mesomelic shortening, hemivertebrae, genital hypoplasia, and "fetal facies". Over 100 cases have now been... (Review)
Review
In 1969, Robinow and colleagues described a syndrome of mesomelic shortening, hemivertebrae, genital hypoplasia, and "fetal facies". Over 100 cases have now been reported and we have reviewed the current knowledge of the clinical and genetic features of the syndrome. The gene for the autosomal recessive form was identified as the ROR2 gene on chromosome 9q22. ROR2 is a receptor tyrosine kinase with orthologues in mouse and other species. The same gene, ROR2, has been shown to cause autosomal dominant brachydactyly B, but it is not known at present whether the autosomal dominant form of Robinow syndrome is also caused by mutations in ROR2.
Topics: Abnormalities, Multiple; Animals; Arm; Dwarfism; Facies; Genotype; Humans; Infant, Newborn; Male; Mice; Mutation, Missense; Penis; Phenotype; Radiography; Rats; Receptor Tyrosine Kinase-like Orphan Receptors; Receptors, Cell Surface; Ribs; Spinal Cord; Syndrome
PubMed: 12011143
DOI: 10.1136/jmg.39.5.305 -
Human Mutation Jul 2022Robinow syndrome is characterized by a triad of craniofacial dysmorphisms, disproportionate-limb short stature, and genital hypoplasia. A significant degree of...
Robinow syndrome is characterized by a triad of craniofacial dysmorphisms, disproportionate-limb short stature, and genital hypoplasia. A significant degree of phenotypic variability seems to correlate with different genes/loci. Disturbances of the noncanonical WNT-pathway have been identified as the main cause of the syndrome. Biallelic variants in ROR2 cause an autosomal recessive form of the syndrome with distinctive skeletal findings. Twenty-two patients with a clinical diagnosis of autosomal recessive Robinow syndrome were screened for variants in ROR2 using multiple molecular approaches. We identified 25 putatively pathogenic ROR2 variants, 16 novel, including single nucleotide variants and exonic deletions. Detailed phenotypic analyses revealed that all subjects presented with a prominent forehead, hypertelorism, short nose, abnormality of the nasal tip, brachydactyly, mesomelic limb shortening, short stature, and genital hypoplasia in male patients. A total of 19 clinical features were present in more than 75% of the subjects, thus pointing to an overall uniformity of the phenotype. Disease-causing variants in ROR2, contribute to a clinically recognizable autosomal recessive trait phenotype with multiple skeletal defects. A comprehensive quantitative clinical evaluation of this cohort delineated the phenotypic spectrum of ROR2-related Robinow syndrome. The identification of exonic deletion variant alleles further supports the contention of a loss-of-function mechanism in the etiology of the syndrome.
Topics: Craniofacial Abnormalities; Dwarfism; Genes, Recessive; Humans; Limb Deformities, Congenital; Male; Phenotype; Receptor Tyrosine Kinase-like Orphan Receptors; Urogenital Abnormalities
PubMed: 35344616
DOI: 10.1002/humu.24375 -
Indian Journal of Orthopaedics Oct 2008Robinow syndrome is a rare autosomal recessive mesomelic dwarfism with just more than 100 cases reported in the literature so far. The lower extremity is spared with...
Robinow syndrome is a rare autosomal recessive mesomelic dwarfism with just more than 100 cases reported in the literature so far. The lower extremity is spared with skeletal deformity usually confined to the forearm, hand, and the dorsal spine. Diagnosis is made easily in the early childhood by the typical "fetal facies" appearance, which disappears to a certain extent as the patient grows. The author reports two cases of this entity with vertebral segmentation defects, rib fusion, and typical severe brachymelia and facial features.
PubMed: 19753239
DOI: 10.4103/0019-5413.43399 -
HGG Advances Jan 2022Robinow syndrome (RS) is a genetically heterogeneous disorder with six genes that converge on the WNT/planar cell polarity (PCP) signaling pathway implicated (, , , , ,...
Robinow syndrome (RS) is a genetically heterogeneous disorder with six genes that converge on the WNT/planar cell polarity (PCP) signaling pathway implicated (, , , , , and ). RS is characterized by skeletal dysplasia and distinctive facial and physical characteristics. To further explore the genetic heterogeneity, paralog contribution, and phenotypic variability of RS, we investigated a cohort of 22 individuals clinically diagnosed with RS from 18 unrelated families. Pathogenic or likely pathogenic variants in genes associated with RS or RS phenocopies were identified in all 22 individuals, including the first variant to be reported in . We retrospectively collected medical records of 16 individuals from this cohort and extracted clinical descriptions from 52 previously published cases. We performed Human Phenotype Ontology (HPO) based quantitative phenotypic analyses to dissect allele-specific phenotypic differences. Individuals with variants clustered into two groups with demonstrable phenotypic differences between those with missense and truncating alleles. Probands with biallelic variants clustered together with the majority of probands carrying , , and variants, demonstrating no phenotypic distinction between the -autosomal recessive and dominant forms of RS. While phenotypically similar diseases on the RS differential matched through HPO analysis, clustering using phenotype similarity score placed RS-associated phenotypes in a unique cluster containing , , and apart from non-RS-associated paralogs. Through human phenotype analyses of this RS cohort and OMIM clinical synopses of Mendelian disease, this study begins to tease apart specific biologic roles for non-canonical WNT-pathway proteins.
PubMed: 35047859
DOI: 10.1016/j.xhgg.2021.100074 -
Case Reports in Obstetrics and... 2022Robinow syndrome is a genetically heterogenous syndrome that exhibits great pleiotropy, involving skeletal genital, cardiac, and craniofacial developmental anomalies....
Robinow syndrome is a genetically heterogenous syndrome that exhibits great pleiotropy, involving skeletal genital, cardiac, and craniofacial developmental anomalies. Fertility is not always compromised, and many individuals may be able to have a healthy pregnancy. Similar to other more common skeletal dysplasias and growth disorders such as achondroplasia, there are several challenges to be addressed in managing physiologic differences that occur in the context of pregnancy, and published literature centers on pregnant people with achondroplasia. We present a patient with Robinow syndrome ( variant), follow her clinical course through three of her pregnancies (one 20-week loss followed by two preterm cesarean deliveries at 36-week gestation), and highlight the major obstetrical considerations in her individualized care.
PubMed: 35909981
DOI: 10.1155/2022/6481517 -
Disease Models & Mechanisms Mar 2023Human Robinow syndrome (RS) and dominant omodysplasia type 2 (OMOD2), characterized by skeletal limb and craniofacial defects, are associated with heterozygous mutations...
Human Robinow syndrome (RS) and dominant omodysplasia type 2 (OMOD2), characterized by skeletal limb and craniofacial defects, are associated with heterozygous mutations in the Wnt receptor FZD2. However, as FZD2 can activate both canonical and non-canonical Wnt pathways, its precise functions and mechanisms of action in limb development are unclear. To address these questions, we generated mice harboring a single-nucleotide insertion in Fzd2 (Fzd2em1Smill), causing a frameshift mutation in the final Dishevelled-interacting domain. Fzd2em1Smill mutant mice had shortened limbs, resembling those of RS and OMOD2 patients, indicating that FZD2 mutations are causative. Fzd2em1Smill mutant embryos displayed decreased canonical Wnt signaling in developing limb mesenchyme and disruption of digit chondrocyte elongation and orientation, which is controlled by the β-catenin-independent WNT5A/planar cell polarity (PCP) pathway. In line with these observations, we found that disruption of FZD function in limb mesenchyme caused formation of shortened bone elements and defects in Wnt/β-catenin and WNT5A/PCP signaling. These findings indicate that FZD2 controls limb development by mediating both canonical and non-canonical Wnt pathways and reveal causality of pathogenic FZD2 mutations in RS and OMOD2 patients.
Topics: Humans; Animals; Mice; Wnt Signaling Pathway; beta Catenin; Osteochondrodysplasias; Facies; Frizzled Receptors
PubMed: 36867021
DOI: 10.1242/dmm.049876 -
Journal of Medical Genetics Apr 1998
Topics: Abnormalities, Multiple; Diagnosis, Differential; Female; Humans; Syndrome
PubMed: 9598742
DOI: 10.1136/jmg.35.4.349-a