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Indian Journal of Ophthalmology Mar 2016Oculodentodigital dysplasia is a rare, autosomal dominant disorder with high penetrance and variable expressivity, caused by mutations in the connexin 43 or gap junction...
Oculodentodigital dysplasia is a rare, autosomal dominant disorder with high penetrance and variable expressivity, caused by mutations in the connexin 43 or gap junction protein alpha-1 gene. It has been diagnosed in fewer than 300 people worldwide with an incidence of around 1 in 10 million. It affects many parts of the body, particularly eyes (oculo), teeth (dento), and fingers and/or toes (digital). The common clinical features include facial dysmorphism with thin nose, microphthalmia, syndactyly, tooth anomalies such as enamel hypoplasia, anodontia, microdontia, early tooth loss and conductive deafness. Other less common features are abnormalities of the skin and its appendages, such as brittle nails, sparse hair, and neurological abnormalities. To prevent this syndrome from being overlooked, awareness of possible symptoms is necessary. Early recognition can prevent blindness, dental problems and learning disabilities. Described here is the case of a 21-year-old male who presented to the ophthalmology outpatient department with a complaint of bilateral progressive loss of vision since childhood.
Topics: Abnormalities, Multiple; Craniofacial Abnormalities; Eye Abnormalities; Foot Deformities, Congenital; Humans; Male; Microphthalmos; Syndactyly; Tooth Abnormalities; Vision, Low; Visual Acuity; Young Adult
PubMed: 27146935
DOI: 10.4103/0301-4738.180191 -
Saudi Journal of Ophthalmology :... 2019To report a critical case series of six patients with posterior microphthalmos (PM).
AIM
To report a critical case series of six patients with posterior microphthalmos (PM).
METHOD
Complete ophthalmologic examinations of all patients were performed using best-corrected visual acuity (BCVA), cycloplegic refraction, applanation tonometry, slit lamp biomicroscopy of the anterior segment, fundoscopy, A and B mode ultrasonography (USG), keratometry, and optic coherence tomography (OCT).
RESULTS
The most significant clinical characteristics of male patients aged 10-25 years was the presence of shorter posterior segments (mean: 15.27-18.91 mm) accompanying high hyperopia (mean +9.00 - +18.50 diopter) despite the normal anterior segment findings. The BCVA ranged between 20/320 and 40/100. Retinal folds were detected bilaterally on the papillomacular band in all patients. Although neurosensory retina was included in the fold in OCT images, retinal pigment epithelium, choroid, and sclera were not included in the fold. Pigmentary retinopathy was detected in one patient.
CONCLUSION
Despite normal anterior segment, posterior microphthalmos is characterized with high hyperopia, and shorter axial length and bilateral papillomacular retinal fold. Refractive amblyopia, uveal effusion syndrome, retinal detachment and macular hole are complications that can be corrected. Posterior microphthalmos must be kept in mind in patients with a normal anterior segment, and high hyperopia.
PubMed: 30930662
DOI: 10.1016/j.sjopt.2018.10.007 -
European Journal of Human Genetics :... Oct 2023Biallelic pathogenic variants in ALDH1A3 are responsible for approximately 11% of recessively inherited cases of severe developmental eye anomalies. Some individuals can...
Biallelic pathogenic variants in ALDH1A3 are responsible for approximately 11% of recessively inherited cases of severe developmental eye anomalies. Some individuals can display variable neurodevelopmental features, but the relationship to the ALDH1A3 variants remains unclear. Here, we describe seven unrelated families with biallelic pathogenic ALDH1A3 variants: four compound heterozygous and three homozygous. All affected individuals had bilateral anophthalmia/microphthalmia (A/M), three with additional intellectual or developmental delay, one with autism and seizures and three with facial dysmorphic features. This study confirms that individuals with biallelic pathogenic ALDH1A3 variants consistently manifest A/M, but additionally display neurodevelopmental features with significant intra- and interfamilial variability. Furthermore, we describe the first case with cataract and highlight the importance of screening ALDH1A3 variants in nonconsanguineous families with A/M.
Topics: Humans; Microphthalmos; Anophthalmos; Mutation; Aldehyde Oxidoreductases; Eye Abnormalities; Phenotype
PubMed: 36997679
DOI: 10.1038/s41431-023-01342-8 -
Indian Journal of Ophthalmology Jul 2022Fraser syndrome is a rare congenital disorder comprising cryptophthalmos, syndactyly, and many times, urogenital anomalies. Herein, the authors aimed to study and report... (Review)
Review
PURPOSE
Fraser syndrome is a rare congenital disorder comprising cryptophthalmos, syndactyly, and many times, urogenital anomalies. Herein, the authors aimed to study and report the clinical features and orbital anomalies in cases diagnosed with Fraser syndrome.
METHODS
The authors retrospectively evaluated the records of patients with Fraser syndrome who had presented to a tertiary eye care hospital in northern India in the last 2 years (from January 2019 to December 2020). The clinical features were studied, entered in MS Excel, and the data was evaluated.
RESULTS
Data of 15 patients with Fraser syndrome were found. Majority of the patients were males and presented in the pediatric age group. Bilateral involvement was more common, and the most common variant of cryptophthalmos was abortive. Complete and medial madarosis of the eyebrows was the most common periocular finding. Complete cryptophthalmos was associated with cystic globes, whereas abortive forms had superior symblepharon. Common systemic features included syndactyly, bifid nose, and urogenital anomaly.
CONCLUSION
Fraser syndrome is an extremely rare developmental disorder; it encompasses a wide range of ocular, periocular, and orbital anomalies, along with multiple pre-existing systemic anomalies. The treating ophthalmologist should always be careful in examining these patients.
Topics: Abnormalities, Multiple; Child; Eyelids; Female; Fraser Syndrome; Humans; Male; Microphthalmos; Rare Diseases; Retrospective Studies; Syndactyly
PubMed: 35791156
DOI: 10.4103/ijo.IJO_2627_21 -
American Journal of Ophthalmology Case... Dec 2020We report a case of posterior microphthalmos with characteristic papillomacular retinal folds, pigmentary retinopathy, and optic disc drusen.
PURPOSE
We report a case of posterior microphthalmos with characteristic papillomacular retinal folds, pigmentary retinopathy, and optic disc drusen.
OBSERVATIONS
A 19-year-old female presented with decreased visual acuity and was found to have bilateral posterior microphthalmos with the presence of papillomacular retinal folds, crowded optic nerves with buried disc drusen, and peripheral retinal pigmentary changes. Optical coherence tomography showed presence of retinal folds involving the inner retinal layers and loss of foveal contour.
CONCLUSIONS AND IMPORTANCE
Posterior microphthalmos can present with an array of unique clinical findings involving the posterior segment. It is important to recognize these findings as these patients often have decreased visual acuity and are at risk for the development of other posterior complications.
PubMed: 32964171
DOI: 10.1016/j.ajoc.2020.100915 -
Ophthalmic Genetics Jun 2021: To describe a family with presumed gonadosomatic mosaicism diagnosed upon ophthalmic examination of the proband's mother.: The family underwent comprehensive...
: To describe a family with presumed gonadosomatic mosaicism diagnosed upon ophthalmic examination of the proband's mother.: The family underwent comprehensive ophthalmic and physical examination. Variant detection was performed using trio exome analysis on peripheral leukocyte DNA from blood and saliva samples. Variant segregation analysis was performed using a custom panel NGS sequencing. An identified variant in the gene was confirmed in the proband by Sanger sequencing.: We report an individual with bilateral microphthalmia, developmental delay, hearing loss, and dysmorphic features. Her mother was found to have asymptomatic uveal coloboma affecting her anterior segment. Her father, aunt, and sisters were unaffected. Trio exome sequence analysis showed an apparent heterozygous deletion in the proband, NM_003106.3:c.70_89del, NP_003097.1:p.(Asn24Argfs*65), classified as pathogenic. Testing of the other family members' peripheral blood and saliva was negative for this variant. The iris transillumination abnormalities in the proband's mother supports a gonadosomatic mosaicism scenario.: The results from this family underscore the importance of performing detailed evaluations of the parents of apparently sporadically affected individuals with heritable ophthalmic disorders. The identification of mildly affected individuals could substantially alter recurrence risks.
Topics: Adult; Craniofacial Abnormalities; Developmental Disabilities; Female; Hearing Loss; High-Throughput Nucleotide Sequencing; Humans; Infant, Newborn; Male; Microphthalmos; Mosaicism; Pedigree; SOXB1 Transcription Factors; Sex Chromosome Disorders; Exome Sequencing
PubMed: 33719903
DOI: 10.1080/13816810.2021.1888127 -
BMJ Case Reports May 2021A 12-year-old girl presented with an unusually large mass under the right lower eyelid and a smaller mass under the left lower lid since the last 6 months. The parents...
Bilateral severe microphthalmos with bilateral colobomatus orbitopalpebral cyst: accessibility of speciality eye-care and rehabilitation services in low and middle-income countries.
A 12-year-old girl presented with an unusually large mass under the right lower eyelid and a smaller mass under the left lower lid since the last 6 months. The parents had noticed the absence of the right eyeball and a very small left eyeball and no vision in both eyes since birth but did not approach the healthcare system. The patient was diagnosed as a case of bilateral severe microphthalmos with colobomatous cyst with late presentation and was treated surgically. The parents were counselled for education and training of the child in schools for visually impaired. Early treatment and rehabilitation help patients lead a normal life in these cases. In rural areas, patients face challenges in getting access to the specialty eye-care services due to several barriers, including lack of availability and affordability. This case highlights the disparities in essential health services in low and middle-income countries.
Topics: Child; Coloboma; Cysts; Developing Countries; Eye; Female; Health Services Accessibility; Humans; Microphthalmos
PubMed: 34031083
DOI: 10.1136/bcr-2021-241783 -
The British Journal of Ophthalmology Nov 2023Microphthalmia, anophthalmia and coloboma (MAC) are clinically and genetically heterogenous rare developmental eye conditions, which contribute to a significant...
BACKGROUND/AIMS
Microphthalmia, anophthalmia and coloboma (MAC) are clinically and genetically heterogenous rare developmental eye conditions, which contribute to a significant proportion of childhood blindness worldwide. Clear understanding of MAC aetiology and comorbidities is essential to providing patients with appropriate care. However, current management is unstandardised and molecular diagnostic rates remain low, particularly in those with unilateral presentation. To further understanding of clinical and genetic management of patients with MAC, we charted their real-world experience to ascertain optimal management pathways and yield from molecular analysis.
METHODS
A prospective cohort study of consecutive patients with MAC referred to the ocular genetics service at Moorfields Eye Hospital between 2017-2020.
RESULTS
Clinical analysis of 50 MAC patients (15 microphthalmia; 2 anophthalmia; 11 coloboma; and 22 mixed) from 44 unrelated families found 44% had additional ocular features (complex) and 34% had systemic involvement, most frequently intellectual/developmental delay (8/17). Molecular analysis of 39 families using targeted gene panels, whole genome sequencing and microarray comparative genomic hybridisation identified genetic causes in, 28% including novel variants in six known MAC genes (, , , , and ), and a molecular diagnostic rate of 33% for both bilateral and unilateral cohorts. New phenotypic associations were found for (bilateral sensorineural hearing loss) and (unilateral microphthalmia).
CONCLUSION
This study highlights the importance of thorough clinical and molecular phenotyping of MAC patients to provide appropriate multidisciplinary care. Routine genetic testing for both unilateral and bilateral cases in the clinic may increase diagnostic rates in the future, helping elucidate genotype-phenotype correlations and informing genetic counselling.
Topics: Humans; Anophthalmos; Microphthalmos; Coloboma; Prospective Studies; Eye Abnormalities; Eye Proteins; Intracellular Signaling Peptides and Proteins
PubMed: 36192130
DOI: 10.1136/bjo-2022-321991 -
Molecular Vision 2011Optic nerve aplasia (ONA, OMIM 165550) is a very rare unilateral or bilateral condition that leads to blindness in the affected eye, and is usually associated with other...
PURPOSE
Optic nerve aplasia (ONA, OMIM 165550) is a very rare unilateral or bilateral condition that leads to blindness in the affected eye, and is usually associated with other ocular abnormalities. Although bilateral ONA often occurs in association with severe congenital anomalies of the brain, nonsyndromic sporadic forms with bilateral ONA have been described. So far, no autosomal-dominant nonsyndromic ONA has been reported. The genetic basis of this condition remains largely unknown, as no developmental genes other than paired box gene 6 (PAX6) are known to be implicated in sporadic bilateral ONA.
METHODS
The individuals reported underwent extensive ophthalmological, endocrinological, and neurologic evaluation, including neuroimaging of the visual pathways. In addition genomewide copy number screening was performed.
RESULTS
Here we report an autosomal-dominant form of nonsyndromic ONA in a Belgian pedigree, with unilateral microphthalmia and ONA in the second generation (II:1), and bilateral ONA in two sibs of the third generation (III:1; III:2). No PAX6 mutation was found. Genome wide copy number screening revealed a microdeletion of maximal 363 kb of chromosome 10q23.33q23.33 in all affected individuals (II:1, III:1; III:2) and in unaffected I:1, containing three genes: exocyst complex component 6 (EXOC6), cytochrome p450, subfamily XXVIA, polypeptide 1 (CYP26A1), and cytochrome p450, subfamily XXVIC, polypeptide 1 (CYP26C1). The latter two encode retinoic acid-degrading enzymes.
CONCLUSIONS
This is the first study reporting an autosomal-dominant form of nonsyndromic ONA. The diagnostic value of neuroimaging in uncovering ONA in microphthalmic patients is demonstrated. Although involvement of other genetic factors cannot be ruled out, our study might point to a role of CYP26A1 and CYP26C1 in the pathogenesis of nonsyndromic ONA.
Topics: Asymptomatic Diseases; Child, Preschool; Chromosome Mapping; Chromosomes, Human, Pair 10; Cytochrome P-450 Enzyme System; Cytochrome P450 Family 26; DNA Mutational Analysis; Eye Proteins; Female; Gene Dosage; Genes, Dominant; Genetic Linkage; Genome-Wide Association Study; Humans; Male; Microphthalmos; Middle Aged; Mutation; Neuroimaging; Optic Nerve; Pedigree; Phenotype; Retinoic Acid 4-Hydroxylase; Tretinoin; Vision Tests
PubMed: 21850183
DOI: No ID Found