Oculofaciocardiodental syndrome: Difference between revisions
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==Historical Aspect of Oculofaciocardiodental Syndrome== | ==Historical Aspect of Oculofaciocardiodental Syndrome== | ||
* Obwegeser and Gorlin (1997), who referred to this condition as the oculofaciocardiodental (OFCD) syndrome, stated that Hayward (1980) was probably the first to report the association of congenital cataracts and radiculomegaly of the canine teeth. Marashi and Gorlin (1990, 1992) reported additional examples.<ref>{{ | * Obwegeser and Gorlin (1997), who referred to this condition as the oculofaciocardiodental (OFCD) syndrome, stated that Hayward (1980) was probably the first to report the association of congenital cataracts and radiculomegaly of the canine teeth. Marashi and Gorlin (1990, 1992) reported additional examples.<ref>{{cite journal|doi=10.1043/0003-3219}}</ref> | ||
* Gorlin et al. (1996) reviewed all reported cases and concluded that the OFCD syndrome consists of (1) eye anomalies (congenital cataract, microphthalmia, or secondary glaucoma); (2) facial abnormalities (long narrow face, high nasal bridge, pointed nose with cartilages separated at the tip, cleft palate, or submucous cleft palate); (3) cardiac anomalies (atrial septal defect, ventricular septal defect, or floppy mitral valve); and (4) dental abnormalities (canine radiculomegaly, delayed dentition, oligodontia, persistent primary teeth, or variable root length). They suggested that inheritance might be X-linked dominant, lethal in the male. The syndrome had been observed in 2 generations and in 7 females but not in males. | * Gorlin et al. (1996) reviewed all reported cases and concluded that the OFCD syndrome consists of (1) eye anomalies (congenital cataract, microphthalmia, or secondary glaucoma); (2) facial abnormalities (long narrow face, high nasal bridge, pointed nose with cartilages separated at the tip, cleft palate, or submucous cleft palate); (3) cardiac anomalies (atrial septal defect, ventricular septal defect, or floppy mitral valve); and (4) dental abnormalities (canine radiculomegaly, delayed dentition, oligodontia, persistent primary teeth, or variable root length). They suggested that inheritance might be X-linked dominant, lethal in the male. The syndrome had been observed in 2 generations and in 7 females but not in males. | ||
Revision as of 23:38, 22 July 2020
| Oculofaciocardiodental syndrome |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Associate Editor in Chief: Berna Zorkun DMD [2]
Synonyms and related keywords: MCOPS2 or Microphthalmia, cataracts, radiculomegaly, and septal heart defects or Microphthalmia, syndromic 2, Oculo-facio-cardio-dental syndrome, OFCD syndrome
Overview
Oculofaciocardiodental syndrome (OFCD) is a rare congenital condition affecting eyes, heart, face and teeth. This syndrome is a X-linked syndrome and it has been seen in heterygous female only. Due to its lethal affects on male, there has been no report of affected male. Common signs ad symptoms include cataract, small deep-set eyes, long narrow face, heart defects and teeth with large roots.
Incidence
Oculofaciocardiodental syndrome is very rare; the incidence is estimated to be less than 1 in 1 million people.
Genetics
The genetic analysis in oculofaciocardiodental syndrome patients shows mutations in BCOR gene on chromosome Xp11.4 which has functions like maintaining tissue homeostasis and gene silencing by epigenetic mechanisms. BCOR gene provides instructions for making BCL6 corepressor protein. The BCL6 corepressor play an essential role in early embryonic development, including the formation of the eyes and several other tissues and organs like cardiovascular system and face tissues. It can also involve in specifying the left and right sides of the body in the developing embryo.[1]
Historical Aspect of Oculofaciocardiodental Syndrome
- Obwegeser and Gorlin (1997), who referred to this condition as the oculofaciocardiodental (OFCD) syndrome, stated that Hayward (1980) was probably the first to report the association of congenital cataracts and radiculomegaly of the canine teeth. Marashi and Gorlin (1990, 1992) reported additional examples.[2]
- Gorlin et al. (1996) reviewed all reported cases and concluded that the OFCD syndrome consists of (1) eye anomalies (congenital cataract, microphthalmia, or secondary glaucoma); (2) facial abnormalities (long narrow face, high nasal bridge, pointed nose with cartilages separated at the tip, cleft palate, or submucous cleft palate); (3) cardiac anomalies (atrial septal defect, ventricular septal defect, or floppy mitral valve); and (4) dental abnormalities (canine radiculomegaly, delayed dentition, oligodontia, persistent primary teeth, or variable root length). They suggested that inheritance might be X-linked dominant, lethal in the male. The syndrome had been observed in 2 generations and in 7 females but not in males.
- Schulze et al. (1999) reviewed the 9 previously reported cases of OFCD syndrome and reported 3 additional female patients. In addition to the known features of the syndrome, fusion of teeth and hyperdontia of permanent upper teeth were seen. Structural and morphologic dental changes were also noted.
- Ng et al. (2002) studied an African American family, previously reported by Hoefnagel et al. (1963) and Ogunye et al. (1975), with 6 affected males exhibiting microphthalmia or clinical anophthalmia associated with the variable features of microcephaly, mental retardation, large posteriorly rotated and anteverted ears, renal aplasia, cryptorchidism, and hypospadias, in an X-linked recessive inheritance pattern consistent with Lenz microphthalmia syndrome (MCOPS1; 309800).
- Hedera and Gorski (2003) described another instance of mother-daughter OFCD transmission. In addition to the clinical features typically seen in OFCD, the affected daughter exhibited several other congenital anomalies including intestinal malrotation and hypoplastic thumbs. The typical features in both were congenital cataracts, microphthalmia, characteristic dental anomalies, and facial dysmorphism. Favoring X-linked dominant inheritance was the finding of a skewed X-chromosome inactivation in both mother and daughter. Similar patterns of nonrandom lyonization have been documented in other X-linked diseases with male hemizygote lethality such as incontinentia pigmenti (308300) and focal dermal hypoplasia (305600).
- Oberoi et al. (2005) reported 2 new cases of the OFCD syndrome characterized by cataracts, microphthalmia, facial anomalies, cleft palate, cardiac septal defects, and canine radiculomegaly. The first patient was a 17-year-old female in whom bilateral cataracts were noted at birth and an atrial septal defect was repaired at age 4 years. She had a long thin face with a prominent nasal bridge and short nasal tip. She had notched alae with a midline crease in the nasal tip, submucous cleft palate, and a single maxillary central incisor. Some primary teeth were retained at the age of 17 years, and eruption pattern was asymmetric, with delayed eruption of the primary teeth. The second patient reported by Oberoi et al. (2005) was found to have bilateral cataracts and a cardiac murmur at birth. She had limited pronation of her left arm secondary to radial-ulnar synostosis. At the age of 9 years, she had a long, narrow face and microphthalmia with ptosis and deep-set eyes with blepharophimosis. The nasal root was narrow with a bulbous and bifid nasal tip. There was delayed eruption of the maxillary permanent central and lateral incisors. The patient had a deletion in the BCOR gene confirmed by molecular analysis.
Diagnosis
Diagnosis of oculofaciocardiodental syndrome is hard for medical specialists and the syndrome is often unrecognized.
Cardiac Abnormalities
- Ventricular septal defect
- Atrial septal defect
- Mild cardiomegaly
- Atrial hypertrophy
- Ventricular hypertrophy
- Benign peripheral pulmonic stenosis
- Mitral valve prolapse
Dental Abnormalities
The specific dental findings (visible on a panoramic radiograph of the jaws) can be easily diagnosed by an orthodontist or a dentist.
- Radiculomegaly: The most consistent and pathognomic dental finding of oculofaciocardiodental syndrome is radiculomegaly (extremely long roots), particularly of the canines and occasionally of other teeth including premolars and incisors.
- Slow and delayed dental eruption: The dental eruption in both the deciduous and the permanent dentition is consistently slow and delayed.
- Oligodontia
- Fused teeth
- Supernumerary teeth
- Malformed permanent teeth
- Enamel defects
- Root dilacerations
- Malposition
- Malocclusion
Facial Abnormalities
- Long narrow face
- High nasal bridge
- Broad nasal tip with separated nasal cartilages
- Laterally curved and thick eyebrows
- Long philtrum
- Clefts of the hard / soft palate
Ocular Abnormalities
- Bilateral congenital cataracts
- Microphthalmia
- Regressive vision impairment
- Secondary glaucoma
- Ptosis
- Exotropia: Exotropia is very common.
Others
- Syndactyly of the second and third toes
- Hammer-type flexion of the second and fourth toes
- Radio-ulnar synostosis
- Vertebral and rib anomalies
- Intestinal malrotation
- Hearing impairment
- Mental and psychomotor retardation
Inheritance
This condition is inherited in an X-linked dominant pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In females (who have two X chromosomes), a mutation in one of the two copies of the gene in each cell is sufficient to cause the disorder. Some cells produce a normal amount of BCL6 co-repressor protein and other cells produce none. The resulting overall reduction in the amount of this protein leads to the signs and symptoms of OFCD syndrome.
In males (who have only one X chromosome), mutations result in a total loss of the BCL6 co-repressor protein. A lack of this protein appears to be lethal very early in development, so no males are born with OFCD syndrome.
Management
Management of oculofaciocardiodental syndrome requires appropriate cardiac, ophthalmic and dental care.
Source
References
- ↑ Hilton, Emma N.; Manson, Forbes D.C.; Urquhart, Jill E.; Johnston, Jennifer J.; Slavotinek, Anne M.; Hedera, Peter; Stattin, Eva-Lena; Nordgren, Ann; Biesecker, Leslie G.; Black, Graeme C.M. (2007). "Left-sided embryonic expression of the BCL-6 corepressor, BCOR, is required for vertebrate laterality determination". Human Molecular Genetics. 16 (14): 1773–1782. doi:10.1093/hmg/ddm125. ISSN 1460-2083.
- ↑ . doi:10.1043/0003-3219. Missing or empty
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