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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 -
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 -
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 -
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 -
Cureus Feb 2024Foveal hypoplasia is a retinal disorder characterized by the anatomic absence of the foveal pit. It might be isolated or associated with poor vision and several...
Foveal hypoplasia is a retinal disorder characterized by the anatomic absence of the foveal pit. It might be isolated or associated with poor vision and several conditions such as albinism, aniridia, microphthalmos, congenital nystagmus, or other diseases. Genetic and non-genetic causes can play a role in foveal pit development. However, the exact mechanism that causes foveal pit absence has not been determined. This study reports a five-year-old boy who presented to the eye clinic with bilateral poor vision since birth. Optical coherence tomography (OCT) was performed and confirmed the absence of the foveal pit in both eyes. Diagnosis of foveal hypoplasia was made. The parents reported a positive family history of similar conditions, specifically, a paternal grandfather, a male paternal cousin, and a brother. To the best of our knowledge, this is the first reported case of foveal hypoplasia, with a positive family history in the male gender specifically. Thus, inheritance is presumed to be X-linked recessive. We acknowledge that further investigation by genetic testing would offer further insight into this case.
PubMed: 38465154
DOI: 10.7759/cureus.53891