A novel deletion mutation, c.1296delT in the BCOR gene, is associated with oculo-facio-cardio-dental syndrome.
Zhang Jingshang,Jia Hongyan,Wang Jinda,Xiong Ying,Li Jing,Li Xiaoxia,Zhao Jing,Zhang Xiaohui,You Qisheng,Zhu Guyu,Tsai Frank F,Espina Mark,Wan Xiuhua
Science China. Life sciences
The purpose of the present study was to analyze the clinical phenotypes of a girl with oculo-facio-cardio-dental (OFCD) syndrome and to identify the potential pathogenic mutation responsible for her disease. The patient underwent detailed clinical examinations and phenotype data were collected over a follow-up period of 9 years. Mutation analysis of the candidate gene BCOR was performed with polymerase chain reaction and Sanger sequencing. BCOR of 60 unrelated normal individuals were also sequenced as a control group. Clinical phenotyping and follow-up study results indicate that this patient had multiple system anomalies including ocular, facial, cardiac, dental, and limb malformations. In addition, papilloma of the choroid plexus was identified, which represents the first report of this phenotype in an OFCD patient. A novel deletion mutation, c.1296delT in exon 4 of the BCOR gene, was identified in this patient and was not found in her parents or in 60 normal unrelated individuals. This deletion was a frameshift mutation and is proposed to encode a premature stop codon, thus producing a truncated protein. Our patient fitted the diagnostic criteria for OFCD syndrome and we report the first papilloma of the choroid plexus in an OFCD patient, expanding the recognized phenotypic spectrum of this disease. Meanwhile, we identified a novel deletion mutation that may cause OFCD syndrome.
10.1007/s11427-018-9374-2
Molecular characterization of co-occurring Duchenne muscular dystrophy and X-linked oculo-facio-cardio-dental syndrome in a girl.
Jiang Yong-hui,Fang Ping,Adesina Adekunle M,Furman Patricia,Johnston Jennifer J,Biesecker Leslie G,Brown Chester W
American journal of medical genetics. Part A
Duchenne muscular dystrophy is an X-linked condition at the severe end of the spectrum of dystrophinopathies. Females with dystrophin mutations are at risk for cardiomyopathy, but are usually asymptomatic during childhood. However, some girls can exhibit features of Duchenne muscular dystrophy because of skewed X-inactivation, aneuploidy, or chromosomal rearrangement. Oculo-facio-cardio-dental syndrome is a rare X-linked disorder, lethal in males, that comprises microphthalmia, congenital cataracts, congenital heart defect, canine radiculomegaly, and digital anomalies. We report on a 7-year-old girl who was referred for muscular hypotonia, with clinical features of Duchenne muscular dystrophy, including elevated serum creatine phosphokinase, pseudohypertrophy of calf muscles, and muscle weakness, which became evident at 3 years of age. In addition, she had multiple congenital anomalies including atrial septal defect, cataracts, dental and digital anomalies, a constellation that suggested the diagnosis of oculo-facio-cardio-dental syndrome, a condition caused by mutations in BCOR. Immunohistochemistry and Western blot analysis of muscle, and mutation analysis of DMD showed a maternally inherited deletion of exons 30-43, confirming the diagnosis of Duchenne muscular dystrophy. Studies of lymphocytes showed essentially complete skewing of X-inactivation. Mutation analysis of BCOR revealed a de novo frameshift mutation (c.1005delC). Thus, we report for the first time on an individual with the co-occurrence of Duchenne muscular dystrophy and oculo-facio-cardio-dental syndrome.
10.1002/ajmg.a.32863
Oculo-facio-cardio-dental syndrome: report of a rare case.
Türkkahraman Hakan,Sarioğlu Mehmet
The Angle orthodontist
Oculo-facio-cardio-dental (OFCD) syndrome is an extremely rare condition with ocular, facial, cardiac, and dental abnormalities. It is often unrecognized by many medical and dental professionals. Only 17 cases have been documented to date. Because all reported patients have been female, it has been suggested that OFCD syndrome is an X-linked dominant trait. Isolation and diagnosis of this syndrome is hard for the medical specialists. Only unique and specific findings are observed in dental and skeletal structures, which can easily be diagnosed by an orthodontist or general dentist. Therefore, it was the aim of this study to present a new case of this syndrome and to evaluate it from an orthodontic perspective in order to call the attention of orthodontists to this rare anomaly.
10.1043/0003-3219(2006)076[0184:OSROAR]2.0.CO;2
Oculo-facio-cardio-dental syndrome in three succeeding generations: genotypic data and phenotypic features.
Lozić B,Ljubković J,Pandurić D Gabrić,Saltvig I,Kutsche K,Krželj V,Zemunik T
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas
Oculo-facio-cardio-dental (OFCD) syndrome is a rare X-linked disorder mainly manifesting in females. Patients show ocular, facial, cardiac, and dental abnormalities. OFCD syndrome is caused by heterozygous mutations in the BCOR gene, located in Xp11.4, encoding the BCL6 co-repressor. We report a Croatian family with four female members (grandmother, mother and monozygotic female twins) diagnosed with OFCD syndrome who carry the novel BCOR mutation c.4438C>T (p.R1480*). They present high intrafamilial phenotypic variability with special regard to cardiac defect and cataract that showed more severe disease expression in successive generations. Clinical and radiographic examination of the mother of the twins revealed a talon cusp involving the permanent maxillary right central incisor. This is the first known report of a talon cusp in OFCD syndrome with a novel mutation in the BCOR gene.
10.1590/s0100-879x2012007500150
Radiculomegaly: a case report of this rare dental finding with review of the associated oculo-facio-cardio-dental syndrome.
Smith Molly Housley,Cohen Donald M,Bhattacharyya Indraneel,Islam Nadim M,Kashtwari Deeba
Oral surgery, oral medicine, oral pathology and oral radiology
BACKGROUND:Radiculomegaly, or root gigantism, is a rare dental abnormality with important clinical implications. It is highly specific for oculo-facio-cardio-dental (OFCD) syndrome, which places dentists at the forefront of diagnosis of this syndrome. Only 1 case of nonsyndromic radiculomegaly has been reported in the literature since the description of OFCD syndrome in 1996. We present the second confirmed, nonsyndromic/nonfamilial case and review the literature for dental treatments in patients with this dental finding. STUDY DESIGN:A review of the English language literature was performed in PubMed for patients with radiculomegaly or OFCD syndrome. Teeth affected by radiculomegaly, gender, orodental findings, presence of OFCD syndrome, and dental treatment methods were recorded. RESULTS:Sixty-seven cases of radiculomegaly and 92 cases of OFCD syndrome were found in the literature. Only 1 confirmed case of nonsyndromic/nonfamilial radiculomegaly had been reported previously. Ten reports described dental treatment or treatment plan details, and even fewer included specific methods. CONCLUSIONS:Because dental anomalies, especially radiculomegaly, are a primary feature of OFCD syndrome, dentists should be aware of the clinical and radiographic features. Radiculomegaly poses a distinct challenge to dentists, and reports of dental therapy provided to these patients are sparse. Early diagnosis of the syndrome may prevent dental challenges and improve prognosis.
10.1016/j.oooo.2018.02.011
A novel deletion mutation in the BCOR gene is associated with oculo-facio-cardio-dental syndrome: a case report.
BMC pediatrics
BACKGROUND:Oculo-facio-cardio-dental syndrome is a rare X-linked dominant syndrome, characterized by radiculomegaly, congenital cataracts, dysmorphic facial features, and congenital heart disease. Because of the rarity, this syndrome could be misdiagnosed by the clinician, especially for the infant who may present only one to two systems involved. CASE PRESENTATION:Here we report a 3-month-old female infant presenting with typical clinical manifestations of oculo-facio-cardio-dental syndrome, like ocular, facial, cardiac, and skeletal abnormalities, and the genetic analyses of the proband and her parents were provided. Genetic evaluations were completed using whole exon sequencing, which revealed a novel heterozygous mutation between exons 7 and 14 of the BCOR gene(OMIM:300485) in this patient but not in her parents. This mutation is likely to encode a premature stop codon producing a truncated protein. Our patient was diagnosed early enough to allow for the cardiac defects to be treated first, and she will be closely followed up to ensure that any new presentations are treated in a timeous manner. CONCLUSION:This patient fits the diagnostic criteria for oculo-facio-cardio-dental syndrome and is the youngest oculo-facio-cardio-dental syndrome patient ever reported, which is most important for her prognosis. In addition, this manuscript also describes a novel potenitally causative mutation for this syndrome.
10.1186/s12887-022-03148-x
[Hair dysplasia in oculo-dento-digital syndrome. Apropos of a mother-daughter case].
Adamski H,Chevrant-Breton J,Odent S,Patoux-Pibouin M,Le Marec B,Laudren A,Urvoy M
Annales de dermatologie et de venereologie
Oculo-dento-digital syndrome (SODD) as defined by Meyer-Schwickerath in 1957 is a rare entity (84 cases) which belongs to ectodermal dysplasias. It consists of: the characteristic features (long face, pinched nose); syndactyly; ocular, dental and bone abnormalities. This entity is usually transmitted on the autosomal dominant mode. We report two cases (a mother and daughter) with polymalformations which we classed as SODD. Furthermore, agenesis of lacrimal duct and genitourinary abnormalities were noted. The mother had a very particular complex hair shaft dysplasia (incomplete pili torti, "tiger tail" aspect, fractures) with alopecia since she was fifteen years old. The daughter's hair was normal at birth. In SODD, fine and sparse hair is often observed (44 p. 100). Only one patient had hair shaft investigation under polarized light: pili annulati and monilethrix were described but not found in our cases. These two reports incite to the systematic hair shaft study in SODD as other ectodermal dysplasia syndromes.
Oculo-facio-cardio-dental (OFCD) syndrome.
Opitz C,Horn D,Lehmann R,Dimitrova T,Fasmers-Henke K
Journal of orofacial orthopedics = Fortschritte der Kieferorthopadie : Organ/official journal Deutsche Gesellschaft fur Kieferorthopadie
The association of facial dysmorphy, congenital cataracts, microphthalmia, heart disease, and dental radiculomegaly is very rare. We describe a girl with atrial septal defect, unilateral congenital cataract, unilateral microphthalmia, radiculomegaly of incisor and canine teeth with open apices and other dental crown anomalies. This combination of symptoms clearly represents a distinct syndrome and has recently been described as oculo-facio-cardio-dental (OFCD) syndrome.
10.1007/bf01317179
Novel mutations in BCOR in three patients with oculo-facio-cardio-dental syndrome, but none in Lenz microphthalmia syndrome.
Horn Denise,Chyrek Magdalena,Kleier Saskia,Lüttgen Sabine,Bolz Hanno,Hinkel Georg-Klaus,Korenke Georg Christoph,Riess Angelika,Schell-Apacik Can,Tinschert Sigrid,Wieczorek Dagmar,Gillessen-Kaesbach Gabriele,Kutsche Kerstin
European journal of human genetics : EJHG
Oculo-facio-cardio-dental (OFCD) syndrome is a rare X-linked dominant condition with male lethality characterized by microphthalmia, congenital cataracts, facial dysmorphic features, congenital heart defects, and dental anomalies. Mutations in BCOR (BCL6 co-repressor) located in Xp11.4 have been described to cause OFCD syndrome. Lenz microphthalmia syndrome is inherited in an X-linked recessive pattern comprising microphthalmia/anophthalmia, mental retardation, malformed ears, digital, skeletal, and urogenital anomalies (synonym: microphthalmia with associated anomalies (MAA)). One locus for MAA has been mapped to Xq27-q28. Nonetheless, linkage and subsequent mutation analysis revealed a single missense mutation (p.P85L) in BCOR in a large family with presumed Lenz microphthalmia syndrome (MAA2). We describe novel mutations in BCOR in three patients with OFCD syndrome, two small deletions (c.2488_2489delAG and c.3286delG) and a submicroscopic deletion of about 60 kb encompassing at least BCOR exons 2-15. No BCOR mutation was detected in eight patients with Lenz microphthalmia syndrome. Our data confirm that BCOR is the causative gene for OFCD syndrome; however, the failure to identify any mutation in patients with Lenz microphthalmia syndrome together with the oligosymptomatic phenotype in the reported MAA2 patients suggest that BCOR is not the major gene for this syndrome.
10.1038/sj.ejhg.5201391
Rare dental abnormalities seen in oculo-facio-cardio-dental (OFCD) syndrome: three new cases and review of nine patients.
Schulze B R,Horn D,Kobelt A,Tariverdian G,Stellzig A
American journal of medical genetics
Oculo-facio-cardio-dental syndrome is a very rare condition. So far, only nine cases have been documented. We report on three additional female patients representing the same entity. The clinical findings were: congenital cataract, microphthalmia/microcornea, secondary glaucoma, vision impairment, ptosis, long narrow face, high nasal bridge, broad nasal tip with separated cartilages, long philtrum, cleft palate, atrial septal defect, ventricular septal defect, and skeletal anomalies. The following dental abnormalities were found: radiculomegaly, delayed dentition, oligodontia, root dilacerations (extension), and malocclusion. For the first time, fusion of teeth and hyperdontia of permanent upper teeth were seen. In addition, structural and morphological dental changes were noted. These findings expand the clinical spectrum of the syndrome.
A case of oculo-facio-cardio-dental syndrome with integrated orthodontic-prosthodontic treatment.
Kawamoto Tatsuo,Motohashi Nobuyoshi,Ohyama Kimie
The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association
OBJECTIVE:Oculo-facio-cardio-dental (OFCD) syndrome is a very rare condition that requires comprehensive dental management because of associated multiple dental anomalies such as canine radiculomegaly, delayed dentition, oligodontia, persistent primary teeth, microdontia, and macrodontia. This report presents a case of OFCD in a Japanese girl (13 years 1 month old). We analyzed cephalograms, panoramic roentgenograms, and dental casts and discuss our integrated orthodontic-prosthodontic treatment. DESIGN:The sizes of the tooth crown and root as well as lateral cephalograms were compared with those from a Japanese control group. The outcome of orthodontic treatment was evaluated by comparing cephalograms taken before and after treatment. RESULTS:Radiculomegaly was found not only in the upper and lower canines but also the upper central incisors and lower first premolars. Macrodontia was found in the upper central incisors, upper canines, lower canines, and lower first premolars. Microdontia was found in the upper lateral incisor. Lateral cephalometric analysis showed a remarkable hypoplastic midface in both the sagittal and vertical dimensions, coupled with a significantly decreased cranial base length and an increased gonial angle. Serial lateral cephalograms during orthodontic treatment from 13 to 23 years of age demonstrated only slight maxillary growth and significant downward mandibular growth with clockwise rotation in addition to pronounced labial tipping of the upper central incisors. CONCLUSIONS:Characteristic dental anomalies together with a unique craniofacial dysmorphology were clarified. Successful oral rehabilitation was achieved by integrated orthodontic-prosthodontic treatment.
10.1597/02-133
Oculo-facio-cardio-dental syndrome in a mother and daughter.
McGovern E,Al-Mudaffer M,McMahon C,Brosnahan D,Fleming P,Reardon W
International journal of oral and maxillofacial surgery
Oculo-facio-cardio-dental (OFCD) syndrome is a rare X-linked dominant syndrome characterized by canine teeth with extremely large roots (radiculomegaly), congenital cataract, dysmorphic facial features and congenital heart disease. A case of mother-daughter vertical transmission of OFCD is reported. Dental findings were important in confirming the diagnosis in the mother.
10.1016/j.ijom.2006.05.001
Three cases of oculo-facio-cardio-dental (OFCD) syndrome.
Tsukawaki Hiroyuki,Tsuji Michiko,Kawamoto Tatsuo,Ohyama Kimie
The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association
OBJECTIVE:Oculo-facio-cardio-dental (OFCD) syndrome is a rare condition with ocular, facial, cardiac, and dental disorders. The purpose of this report is to describe three Japanese female patients by using facial measurements, tooth measurements, and cephalometric analysis. DESIGN:Facial measurements, tooth measurements, and the results of cephalometric analyses were compared with Japanese standards using panoramic roentgenograms, dental casts, and lateral cephalograms. RESULTS:A long face and thick upper and lower lips were noted for all cases from facial measurements, and a long crown length and long dental root were noted for all cases from tooth measurements. Relative mandibular protrusion and a large anterior lower facial height, accompanied by a steep mandible and large gonial angle, were seen from the cephalometric analyses. CONCLUSIONS:The results of a long face and long dental root were in accordance with previous reports. In addition, thick upper and lower lips, relative mandibular protrusion, large anterior lower facial height accompanied by a steep mandible, and a large gonial angle may be characterized as specific features of this syndrome.
10.1597/04-089r.1
Patient with oculo-facio-cardio-dental syndrome treated with surgical orthodontics.
Sakaguchi Katsuyoshi,Yagi Takakazu,Nagata Junko,Kubota Takeshi,Sugihara Kazumasa,Miyawaki Shouichi
American journal of orthodontics and dentofacial orthopedics : official publication of the American Association of Orthodontists, its constituent societies, and the American Board of Orthodontics
Oculo-facio-cardio-dental (OFCD) syndrome is a rare syndrome characterized by ocular, facial, cardiac, and dental disorders. Only about 20 cases have been reported to date. The most prominent of the various features of this syndrome is canine radiculomegaly. Other features include a long and narrow face, a high nasal bridge, a broad and pointed nose, a bifid nose, ear deformity, cleft palate or submucous cleft palate, maxillary growth retardation, a large gonial angle, open apices, delayed eruption, persistent deciduous teeth, extreme overbite, and constricted maxilla. Orthodontic and prosthodontic treatment has been reported for several patients, but surgical-orthodontic treatment for OFCD has not been reported. An 18-year-old woman with skeletal Class III malocclusion and OFCD syndrome was treated with edgewise appliance therapy combined with orthognathic surgery. We applied a light force during the treatment so as not to induce ankylosis. At the end of the surgical and orthodontic treatments, functional occlusion and an improved facial profile were achieved. After the retention period, stomatognathic function was improved. The results of this treatment suggest that surgical-orthodontic treatment is an effective method for improving skeletal disharmony, facial profile, occlusion, and stomatognathic function in patients with OFCD.
10.1016/j.ajodo.2011.10.020
Oculo-Facio-Cardio-Dental Syndrome: A Case Report about a Rare Pathological Condition.
Martinho José,Ferreira Hugo,Paulo Siri,Paula Anabela,Marto Carlos-Miguel,Carrilho Eunice,Marques-Ferreira Manuel
International journal of environmental research and public health
(1) Background: Oculo-facio-cardio-dental (OFCD) syndrome is a rare pathological condition with an X-linked dominant trait that only occurs in females; no males are born with OFCD syndrome. This syndrome is characterized by congenital cataracts with secondary glaucoma ocular defects, ventricular and atrial septal defects, or mitral valve prolapses. Facial traits are a long narrow face and a high nasal bridge with a bifid nasal tip. Dental anomalies include radiculomegaly, oligodontia, root dilacerations, malocclusion, and delayed eruption. (2) Methods: This clinical report describes a 26-year-old girl who suffers from OFCD syndrome and who was treated with a multidisciplinary approach. The treatment plan included orthodontic treatment, orthognathic surgery, namely LeFort I and a Bilateral Sagittal Split Osteotomy, and occlusal rehabilitation with implants. (3) Discussion: Early diagnosis and multidisciplinary treatment of orthodontic, orthognathic surgery and occlusal rehabilitation with implants make it possible to maintain tooth function and improve aesthetics with good prognoses for success. In this paper, we report a case of a female patient with OFCD syndrome, who was referred for orthodontic treatment and occlusal rehabilitation and treated with a multidisciplinary approach.
10.3390/ijerph16060928
Oculo-facio-cardio-dental (OFCD) syndrome: the first Italian case of BCOR and co-occurring OTC gene deletion.
Di Stefano C,Lombardo B,Fabbricatore C,Munno C,Caliendo I,Gallo F,Pastore L
Gene
Oculo-facio-cardio-dental (OFCD) syndrome is a rare genetic disorder affecting ocular, facial, dental and cardiac systems. The syndrome is an X-linked dominant trait and it might be lethal in males. This syndrome is usually caused by mutations in the BCL6 interacting co-repressor gene (BCOR). We described a female child with mild phenotype of oculo-facio-cardio-dental syndrome. Array-comparative genomic hybridization (a-CGH) analysis revealed a de novo heterozygous deletion in the Xp11.4 region of approximately 2.3 Mb, involving BCOR and ornithine carbamoyl-transferase (OTC) genes. The deletion observed was subsequently confirmed by real time PCR. In this study we report a first case with co-occurrence of BCOR and OTC genes completely deleted in OFCD syndrome.
10.1016/j.gene.2015.01.044
A rare syndrome with unusual dental findings: Oculo-facio-cardio-dental syndrome.
Verma Geeta,Singh Gulshan Kumar,Tandon Pradeep,Verma Sneh Late
Journal of oral and maxillofacial pathology : JOMFP
Radiculomegaly of a tooth is a rare condition. When it is associated with other dental abnormalities, facial dysmorphism and congenital cataracts, the condition is named as oculofaciocardiodental (OFCD) syndrome. This is an X-linked dominant trait, reported only in women, suggesting that it is lethal in males. The most consistent and pathognomic dental finding of OFCD is radiculomegaly (extremely long roots), particularly of the canines and occasionally of other teeth including premolars and incisors, which can easily be diagnosed on dental panoramic radiographs by a dentist or an orthodontist. Till date, 21 cases have been reported worldwide. The aim of this report is to present a new case of a 24 year old female affected by this syndrome and to evaluate it from a dental perspective to call the attention of dentists to this rare anomaly.
10.4103/0973-029X.140928