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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 -
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 -
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 -
International Journal of Applied &... 2021Dandy-Walker Syndrome (D-WS) is a rare disorder with an incidence of 1%-2% of all central nervous system anomalies. The diagnosis can be challenging, especially in the...
Dandy-Walker Syndrome (D-WS) is a rare disorder with an incidence of 1%-2% of all central nervous system anomalies. The diagnosis can be challenging, especially in the prenatal period. Here, we present an extremely rare case of D-WS associated with bilateral congenital cataracts. A 36 weeks and 6 days old male baby presented with a Dandy-Walker variant associated with bilateral congenital cataract. Ophthalmological examination revealed microphthalmos and congenital cataracts present in both eyes with sclerocornea, iris coloboma, and zone 3 retinopathy of prematurity involving only the right eye. However, the right eye was salvageable. Skull transillumination was negative with no cranial bruit. He was admitted to the neonatal intensive care unit with breathing difficulties, maintained SpO with oxygen through prongs, and noninvasive continuous positive airway pressure for 7 days. He had two episodes of hypoglycemia with hypothermia. There was no significant finding in sepsis evaluation. The abdominal ultrasonography was normal. Echocardiogram was suggestive of patent foramen ovale. Mother's torch panel tested positive for cytomegalovirus immunoglobulin G antibodies. Magnetic resonance imaging brain suggested variant D-WS with dilation of cerebellar fossa and occipital lateral ventricle horn and lack of usual corpus callus structure. Intravenous antibiotics cefotaxime and amikacin were administered along with fluid supplementation. He was shifted to mother feed. The neonate was referred to the pediatric surgery department for further management.
PubMed: 34912695
DOI: 10.4103/ijabmr.ijabmr_343_21 -
Journal of AAPOS : the Official... Dec 2021We report the case of a 4-month-old boy diagnosed with DiGeorge syndrome with novel ocular features. The patient was diagnosed through genetic testing, with a noted...
We report the case of a 4-month-old boy diagnosed with DiGeorge syndrome with novel ocular features. The patient was diagnosed through genetic testing, with a noted 22q11.2 deletion, and had the additional clinical findings of cardiac anomalies, Hirschsprung's disease, and intracranial microhemorrhages. Eye findings included bilateral microphthalmia, persistent fetal vasculature, chorioretinal coloboma, and a unilateral orbital cyst. Given no known additional inciting exposures, a dysgenic mechanism resulting in failed closure of developmental fissures associated with the chromosomal deletion likely gave rise to these combined pathologies.
Topics: Chromosome Deletion; Cysts; DiGeorge Syndrome; Humans; Infant; Male; Microphthalmos; Orbital Diseases
PubMed: 34597781
DOI: 10.1016/j.jaapos.2021.06.001 -
International Journal of Molecular... Feb 2021EPHA2 is a transmembrane tyrosine kinase receptor that, when disrupted, causes congenital and age-related cataracts. Cat-Map reports 22 pathogenic variants associated...
EPHA2 is a transmembrane tyrosine kinase receptor that, when disrupted, causes congenital and age-related cataracts. Cat-Map reports 22 pathogenic variants associated with congenital cataracts, variable microcornea, and lenticonus, but no previous association with microphthalmia (small, underdeveloped eye, ≥2 standard deviations below normal axial length). Microphthalmia arises from ocular maldevelopment with >90 monogenic causes, and can include a complex ocular phenotype. In this paper, we report two pathogenic variants in unrelated families presenting with bilateral microphthalmia and congenital cataracts. Whole genome sequencing through the 100,000 Genomes Project and cataract-related targeted gene panel testing identified autosomal dominant heterozygous mutations segregating with the disease: (i) missense c.1751C>T, p.(Pro584Leu) and (ii) splice site c.2826-9G>A. To functionally validate pathogenicity, morpholino knockdown of / in zebrafish resulted in significantly reduced eye size ± cataract formation. Misexpression of N-cadherin and retained fibre cell nuclei were observed in the developing lens of the knockdown morphant fish by 3 days post-fertilisation, which indicated a putative mechanism for microphthalmia pathogenesis through disruption of cadherin-mediated adherens junctions, preventing lens maturation and the critical signals stimulating eye growth. This study demonstrates a novel association of with microphthalmia, suggesting further analysis of pathogenic variants in unsolved microphthalmia cohorts may increase molecular diagnostic rates.
Topics: Adolescent; Adult; Alternative Splicing; Animals; Cataract; Child; Embryo, Nonmammalian; Ephrin-A2; Female; High-Throughput Nucleotide Sequencing; Humans; Male; Microphthalmos; Middle Aged; Morpholinos; Mutation, Missense; Oligonucleotides, Antisense; Pedigree; Receptor, EphA2; Zebrafish; Zebrafish Proteins
PubMed: 33671840
DOI: 10.3390/ijms22042190 -
The Pan African Medical Journal 2022
Topics: Humans; Microphthalmos; Siblings; Anophthalmos
PubMed: 36523275
DOI: 10.11604/pamj.2022.43.69.35059