-
Journal of Medical Case Reports Jan 2024Oculo-facio-cardio-dental (OFCD) syndrome is a rare condition that affects the eyes, face, heart, and teeth of patients. One notable dental characteristic of OFCD is...
BACKGROUND
Oculo-facio-cardio-dental (OFCD) syndrome is a rare condition that affects the eyes, face, heart, and teeth of patients. One notable dental characteristic of OFCD is radiculomegaly, or root gigantism, which highlights the role of dentists in detecting this syndrome. OFCD is an X-linked dominant syndrome that results from a variant in the BCOR gene. Our study presents the first documented case of OFCD in Vietnam and reports a novel BCOR gene variant observed in this case.
CASE PRESENTATION
A 19-year-old Vietnamese female patient with an extremely long root with an abscess was clinically examined for the expression of OFCDs. The radiograph and the variant in BCOR gene were also evaluated. We identified abnormalities in the teeth, as well as ocular, facial, and cardiac features, with radiculomegaly of the canines being a specific symptom for OFCDs. The patient's genetic analysis revealed a pathogenic heterozygous deletion at intron 11 of the BCOR gene, representing a novel variant.
CONCLUSION
Oculo-facio-cardio-dental syndrome (OFCD) is an extremely rare condition characterized by abnormalities in the eyes, face, heart, and teeth, often caused by variants in the BCOR gene. Radiculomegaly, or enlarged dental roots, is a key diagnostic feature of OFCD, and early detection is crucial for preventing future dental complications.
Topics: Female; Humans; Young Adult; Eye Abnormalities; Face; Heart Defects, Congenital; Heart Septal Defects; Microphthalmos; Syndrome
PubMed: 38178193
DOI: 10.1186/s13256-023-04244-x -
European Journal of Medical Genetics Feb 2024Infants with anophthalmia and microphthalmia (an/microphthalmia) have often other associated congenital anomalies. The reported frequency and the types of these...
Infants with anophthalmia and microphthalmia (an/microphthalmia) have often other associated congenital anomalies. The reported frequency and the types of these associated anomalies vary between different studies. The purpose of this investigation was to assess the frequency and the types of associated anomalies among cases with an/microphthalmia in a geographically well defined population of northeastern France of 387,067 consecutive pregnancies from 1979 to 2007. Of the 98 infants with an/microphthalmia born during this period (prevalence at birth of 2.53 per 10,000), 88.8 % had associated anomalies. Cases with associated anomalies were divided into recognizable conditions (25 (25.5%) cases with chromosomal and 17 (17.3%) cases with non chromosomal conditions), and non recognizable conditions (45-45.9%- cases with multiple congenital anomalies -MCA). Trisomy 13 and trisomy 18 were the most frequent chromosomal abnormalities. Amniotic bands sequence, oculo-auriculo-vertebral spectrum, CHARGE syndrome and VACTERL association were most often present in recognizable non chromosomal conditions. Anomalies in the musculoskeletal, cardiovascular and central nervous systems were the most common other anomalies in cases with MCA and non recognizable conditions. However, given the limitation of the limited numbers of cases there should be urging caution in interpreting these results. In conclusion the frequency of associated anomalies in infants with anophthalmia and microphthalmia emphasizes the need for a thorough investigation of these cases. Routine screening for other anomalies especially musculoskeletal, cardiac and central nervous systems anomalies may need to be considered in infants with anophthalmia and microphthalmia, and referral of these cases for genetic counselling seems warranty.
Topics: Infant; Infant, Newborn; Pregnancy; Female; Humans; Anophthalmos; Microphthalmos; Heart Defects, Congenital; Limb Deformities, Congenital; CHARGE Syndrome; Prevalence
PubMed: 38110175
DOI: 10.1016/j.ejmg.2023.104892 -
Oman Journal of Ophthalmology 2023Achondroplasia is an autosomal dominant congenital disorder of endochondral ossification, induced by abnormal activity of fibroblast growth factor receptor 3. Affected...
Achondroplasia is an autosomal dominant congenital disorder of endochondral ossification, induced by abnormal activity of fibroblast growth factor receptor 3. Affected individuals have short stature and often present with neurological and skeletal complications. Most have normal intelligence. Ocular association with achondroplasia include simple microphthalmos, congenital-onset glaucoma with presumed Axenfeld-Rieger anomaly, telecanthus, exotropia, inferior oblique overaction, angle anomalies, Duane retraction syndrome, cone-rod dystrophy, fundus albipunctatus, chorioretinal coloboma, macular coloboma, keratoconus, and developmental cataract. A 6-year-old achondroplasia boy with developmental delay had a high axial length (high myopia) in both eyes. This child had a left eye subluxated cataractous lens, while the other eye showed mild lens changes. All achondroplasia patients should be routinely screened in detail for lens and other ophthalmological anomalies so that they can undergo timely intervention and management.
PubMed: 38059098
DOI: 10.4103/ojo.ojo_42_23 -
BMC Ophthalmology Oct 2023We report a case of uveal effusion in a nanophthalmic eye after topical use of brimonidine.
BACKGROUND
We report a case of uveal effusion in a nanophthalmic eye after topical use of brimonidine.
CASE PRESENTATION
A 42-year-old male patient with nanophthalmos experienced sudden blurred vision in the right eye after using topical brimonidine when picking up tennis balls repeatedly 6 weeks after bilateral YAG peripheral iridotomy. Ocular examination showed wide choroidal and exudative retinal detachment in the temporal and inferior region, involving the macula. Acute uveal effusion in the right, bilateral nanophthalmos was diagnosed. Oral and topical corticosteroids, combined with topical nonsteroids and atropine led to a complete resolution of the uveal effusion after one month.
CONCLUSION
This case suggested a possible causal relationship between the topical use of brimonidine and acute uveal effusion in patients with nanophthalmos. Topical brimonidine should be used with caution in nanophthalmic eyes.
Topics: Male; Humans; Adult; Microphthalmos; Brimonidine Tartrate; Choroid; Choroid Diseases; Ophthalmologic Surgical Procedures
PubMed: 37814274
DOI: 10.1186/s12886-023-03107-9 -
BMC Ophthalmology Sep 2023Microophthalmos or 'dwarf eye' is characterized by an axial length 2 standard deviation less than age-matched controls. It is classified into nanophthalmos, relative...
BACKGROUND
Microophthalmos or 'dwarf eye' is characterized by an axial length 2 standard deviation less than age-matched controls. It is classified into nanophthalmos, relative anterior microphthalmos, and posterior microphthalmos based on the anterior segment: posterior segment ratio. Nanophthalmos can occur in association with optic disc drusen, foveoschisis, and retinitis pigmentosa, as an autosomal recessive syndrome linked to mutations in the MFRP gene. We report a case of bilateral nanophthalmos and pigmentary retinopathy with angle closure glaucoma and optic disc pit in one eye. We believe this to be the first case presenting with optic disc pit in association with nanophthalmos.
CASE PRESENTATION
A 56-year-old female presented with bilateral small eyes, high hypermetropia, shallow anterior chamber depth, increased lens thickness, mid-peripheral retinal flecks, and macular edema. She also had high intraocular pressure in the right eye, with a disc cupping of 0.9 with an Optic disc pit. The macular edema in the right eye was found to occur in association with the Optic disc pit, whereas, in the left eye, it was associated with intra-retinal hemorrhages and diagnosed as macular branch retinal vein occlusion secondary to hypertension. She was started on anti-glaucoma medications in both eyes and planned for Anti-VEGF injection in the left eye.
CONCLUSION
This case report is unique as it reports an association of Nanophthalmos with Optic Disc pit, with an associated angle closure glaucoma in the same eye, an association which has never been previously reported in the literature.
Topics: Female; Humans; Middle Aged; Microphthalmos; Optic Disk; Glaucoma, Angle-Closure; Macular Edema; Eye Abnormalities; Retinitis Pigmentosa; Membrane Proteins
PubMed: 37752465
DOI: 10.1186/s12886-023-03132-8 -
Klinische Monatsblatter Fur... Mar 2024Congenital aniridia is a severe malformation of almost all eye segments. In addition, endocrinological, metabolic, and central nervous systems diseases may be present....
PURPOSE
Congenital aniridia is a severe malformation of almost all eye segments. In addition, endocrinological, metabolic, and central nervous systems diseases may be present. In order to develop better treatment options for this rare disease, an aniridia center must be established. The purpose of this work is to summarize ophthalmic findings of aniridia subjects examined at the Department of Ophthalmology, Saarland University Medical Center in Homburg.
METHODS
Our retrospective single-center study included patients who underwent a comprehensive ophthalmic examination through the head of the KiOLoN ("Kinderophthalmologie", Orthoptics, Low Vision and Neuroophthalmology) Unit of the department between June 2003 and January 2022. Data at the first examination time point have been included.
RESULTS
Of 286 subjects, 556 eyes of (20.1 ± 20.1 years; 45.5% males) were included. There was nystagmus in 518 (93.7%) eyes, and strabismus in 327 (58.8%) eyes. There were 436 (78.4%) eyes with age-appropriate axial length, 104 (18.7%) eyes with microphthalmos, and 13 (2.3%) eyes with buphthalmos. There was iris malformation with atypical coloboma in 34 eyes (6.1%), more than 6 clock hours of iris remnants in 61 eyes (10.9%), less than 6 clock hours of iris remnants in 96 eyes (17.2%), and complete aniridia in 320 (57.5%) eyes. The patients were graded according to the following aniridia-associated keratopathy (AAK) stages: Stage 0 (96 eyes [17.2%], no keratopathy), Stage 1 (178 eyes [32.0%]), Stage 2 (107 eyes [19.2%]), Stage 3 (67 eyes [12.0%]), Stage 4 (62 eyes [11.1%]), Stage 5 (45 eyes [8.0%]). There was secondary glaucoma in 307 (55.5%), macular hypoplasia in 395 (71.4%), and congenital optic nerve head pathology in 223 (40.3%) eyes. The iris malformation type was significantly positively correlated with AAK stage, lens properties, presence of glaucoma, congenital macular, and optic nerve head properties (p < 0.001 for all), while complete aniridia showed the most complications.
CONCLUSIONS
At the Homburg Aniridia Center, the most common ophthalmic signs in congenital aniridia were AAK, iris malformation, cataract, and macular hypoplasia. The iris malformation type may indicate future expression of AAK, cataract, and glaucoma development and it is correlated with a congenital optic nerve head and macular pathology. Our registry will support further detailed longitudinal analysis of ophthalmic and systemic diseases of aniridia subjects during long-term follow-up.
Topics: Male; Humans; Aged, 80 and over; Female; Cross-Sectional Studies; Retrospective Studies; Aniridia; Cataract; Corneal Diseases; Glaucoma; Vision Disorders
PubMed: 37647922
DOI: 10.1055/a-2065-8405 -
Genes Aug 2023Anophthalmia and microphthalmia (A/M) are among the most severe congenital developmental eye disorders. Despite the advancements in genome screening technologies, more...
Anophthalmia and microphthalmia (A/M) are among the most severe congenital developmental eye disorders. Despite the advancements in genome screening technologies, more than half of A/M patients do not receive a molecular diagnosis. We included seven consanguineous families affected with A/M from Pakistani cohort and an unknown molecular basis. Single gene testing of was performed, followed by genome sequencing for unsolved probands in order to establish a genetic diagnosis for these families. All seven families were provided with a genetic diagnosis. The identified variants were all homozygous, classified as (likely) pathogenic and present in an A/M-associated gene. Targeted sequencing revealed two previously reported pathogenic variants in four families. In the remaining families, genome sequencing revealed a known pathogenic variant, a novel 13bp deletion in , and one novel deep intronic splice variant in . An in vitro splice assay was performed for the splice variant which revealed a severe splicing defect. Our study confirmed the utility of genome sequencing as a diagnostic tool for A/M-affected individuals. Furthermore, the identification of a novel deep intronic pathogenic variant in highlights the role of non-coding variants in A/M-disorders and the value of genome sequencing for the identification of this type of variants.
Topics: Humans; Anophthalmos; Microphthalmos; Chromosome Mapping; Genetic Testing; Eye Abnormalities
PubMed: 37628625
DOI: 10.3390/genes14081573 -
Annual Review of Genomics and Human... Aug 2023The axial length of the eye is critical for normal visual function by enabling light to precisely focus on the retina. The mean axial length of the adult human eye is... (Review)
Review
The axial length of the eye is critical for normal visual function by enabling light to precisely focus on the retina. The mean axial length of the adult human eye is 23.5 mm, but the molecular mechanisms regulating ocular axial length remain poorly understood. Underdevelopment can lead to microphthalmia (defined as a small eye with an axial length of less than 19 mm at 1 year of age or less than 21 mm in adulthood) within the first trimester of pregnancy. However, continued overgrowth can lead to axial high myopia (an enlarged eye with an axial length of 26.5 mm or more) at any age. Both conditions show high genetic and phenotypic heterogeneity associated with significant visual morbidity worldwide. More than 90 genes can contribute to microphthalmia, and several hundred genes are associated with myopia, yet diagnostic yields are low. Crucially, the genetic pathways underpinning the specification of eye size are only now being discovered, with evidence suggesting that shared molecular pathways regulate under- or overgrowth of the eye. Improving our mechanistic understanding of axial length determination will help better inform us of genotype-phenotype correlations in both microphthalmia and myopia, dissect gene-environment interactions in myopia, and develop postnatal therapies that may influence overall eye growth.
Topics: Adult; Female; Pregnancy; Humans; Microphthalmos; Myopia; Gene-Environment Interaction; Multiple Birth Offspring; Pregnancy Trimester, First
PubMed: 37624667
DOI: 10.1146/annurev-genom-102722-090617 -
Genes Jul 2023Mutations in the mouse microphthalmia-associated transcription factor () gene affect retinal pigment epithelium (RPE) differentiation and development and can lead to...
Mutations in the mouse microphthalmia-associated transcription factor () gene affect retinal pigment epithelium (RPE) differentiation and development and can lead to hypopigmentation, microphthalmia, deafness, and blindness. For instance, an association has been established between loss-of-function mutations in the mouse gene and a variety of human retinal diseases, including Waardenburg type 2 and Tietz syndromes. Although there is evidence showing that mice with the homozygous mutation manifest microphthalmia and osteopetrosis, there are limited or no data on the effects of the heterozygous condition in the eye. mice can therefore be regarded as an important model system for the study of human disease. Thus, we characterized mice at 1, 3, 12, and 18 months old in comparison with age-matched wild-type mice. The light- and dark-adapted electroretinogram (ERG) recordings showed progressive cone-rod dystrophy in mice. The RPE response was reduced in the mutant in all age groups studied. Progressive loss of pigmentation was found in mice. Histological retinal sections revealed evidence of retinal degeneration in mice at older ages. For the first time, we report a mouse model of progressive cone-rod dystrophy and RPE dysfunction with a mutation in the gene.
Topics: Animals; Mice; Cone-Rod Dystrophies; Microphthalmia-Associated Transcription Factor; Microphthalmos; Retinal Dystrophies; Retinal Pigment Epithelium
PubMed: 37510362
DOI: 10.3390/genes14071458 -
Scientific Reports Jul 2023Nanophthalmos is characterised by shorter posterior and anterior segments of the eye, with a predisposition towards high hyperopia and primary angle-closure glaucoma....
Nanophthalmos is characterised by shorter posterior and anterior segments of the eye, with a predisposition towards high hyperopia and primary angle-closure glaucoma. Variants in TMEM98 have been associated with autosomal dominant nanophthalmos in multiple kindreds, but definitive evidence for causation has been limited. Here we used CRISPR/Cas9 mutagenesis to recreate the human nanophthalmos-associated TMEM98 p.(Ala193Pro) variant in mice. The p.(Ala193Pro) variant was associated with ocular phenotypes in both mice and humans, with dominant inheritance in humans and recessive inheritance in mice. Unlike their human counterparts, p.(Ala193Pro) homozygous mutant mice had normal axial length, normal intraocular pressure, and structurally normal scleral collagen. However, in both homozygous mice and heterozygous humans, the p.(Ala193Pro) variant was associated with discrete white spots throughout the retinal fundus, with corresponding retinal folds on histology. This direct comparison of a TMEM98 variant in mouse and human suggests that certain nanophthalmos-associated phenotypes are not only a consequence of a smaller eye, but that TMEM98 may itself play a primary role in retinal and scleral structure and integrity.
Topics: Animals; Humans; Mice; Fundus Oculi; Glaucoma, Angle-Closure; Hyperopia; Membrane Proteins; Microphthalmos; Phenotype
PubMed: 37419942
DOI: 10.1038/s41598-023-37855-x