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European Journal of Pediatrics Jun 2023Oculocutaneous albinism (OCA) is a group of rare, genetic disorders caused by absent/reduced melanin biosynthesis. The aim of this study was to explore the neurovisual,...
UNLABELLED
Oculocutaneous albinism (OCA) is a group of rare, genetic disorders caused by absent/reduced melanin biosynthesis. The aim of this study was to explore the neurovisual, cognitive, adaptive, and behavioral profile of children affected by OCA, also evaluating any possible effect of the visual acuity deficit on the clinical profile and genotype-phenotype correlations. Eighteen children (9 males, mean age 84 months ± 41; range 18-181 months) with a molecular confirmed diagnosis of OCA were enrolled in the study. We collected data on clinical history, neurodevelopmental profile, neurological and neurovisual examination, and cognitive, adaptive, and emotional/behavioral functioning. A global neurodevelopmental impairment was detected in 56% of the children, without evolving into an intellectual disability. All the patients showed signs and symptoms of visual impairment. Low adaptive functioning was observed in 3 cases (17%). A risk for internalizing behavioral problems was documented in 6 cases (33%), for externalizing problems in 2 (11%), and for both in 5 (28%). Twelve children (67%) showed one or more autistic-like features. Correlation analyses revealed significant associations between the visual acuity level and performance intelligence quotient (p = 0.001), processing speed index (p = 0.021), Vineland total score (p = 0.020), Vineland communication (p = 0.020), and socialization (p = 0.037) domains. No significant correlations were found between genotype and phenotype.
CONCLUSION
Children with OCA may present a global neurodevelopmental delay that seems to improve with age and emotional/behavioral difficulties, along with the well-known visual impairment. An early neuropsychiatric evaluation and habilitative training are recommended to improve vision-related performance, neurodevelopment, and any psychological difficulties.
WHAT IS KNOWN
• Children with oculocutaneous albinism show dermatological and ophthalmological problems. • An early visual impairment may have negative implications on motor, emotional, and cognitive processes that would allow the child to organize his or her experiences.
WHAT IS NEW
• In addition to a variable combination of ocular signs and symptoms, children with oculocutaneous albinism may present an early neurodevelopmental delay and emotional/behavioral difficulties. • An early visual treatment is recommended to improve vision-related performance, neurodevelopment, and any psychological difficulties.
Topics: Male; Female; Humans; Albinism, Oculocutaneous; Visual Acuity; Genetic Association Studies; Emotions; Vision Disorders
PubMed: 37009951
DOI: 10.1007/s00431-023-04938-w -
Saudi Journal of Ophthalmology :... 2023The objective of this study on patients with albinism in different age groups was to compare their level of visual impairment with the low-vision intervention (LVI) and...
PURPOSE
The objective of this study on patients with albinism in different age groups was to compare their level of visual impairment with the low-vision intervention (LVI) and its benefit.
METHODS
The medical records of 72 patients with low vision secondary to albinism who were referred to the low vision care clinic from 2015 to 2017 were analyzed. This included the demographic profile such as age, gender, occupation, ocular history, visual acuity status, and type of low-vision device (LVD) preferred. The LVDs prescribed and its subsequent improvement was compared.
RESULTS
In this data, 70 (97.2%) people had oculocutaneous albinism and 2 (2.8%) had ocular albinism. Majority of the patients had hyperopic astigmatism 42 (58.3%) and with-the-rule astigmatism 58 (93.5%). Presenting mean visual acuity for distance was noted to be 0.88 logMAR which improved to 0.83 logMAR with the help of spectacle correction. The most commonly prescribed LVD was a dome magnifier for 15 (34.9%) patients. In all the patients, there was statistically significant improvement ( < 0.05) in near vision with the help of LVDs.
CONCLUSION
The study highlights the importance of appropriate LVI for each subdivided age group. Patients with albinism who have received medical and surgical treatment have no or a limited role in restoring useful vision.
PubMed: 36968775
DOI: 10.4103/sjopt.sjopt_266_21 -
Saudi Journal of Ophthalmology :... 2023The purpose of the study was to analyze the demographics, visual acuity (VA), etiologies, recommended low vision assistive products (LVAP), and the acceptance rates of...
PURPOSE
The purpose of the study was to analyze the demographics, visual acuity (VA), etiologies, recommended low vision assistive products (LVAP), and the acceptance rates of LVAP in various age groups.
METHODS
This was a long-term retrospective review of all the patients presenting to the low vision clinic of our tertiary eye care hospital from January 2011 to December 2016. Data obtained included age, gender, VA, visual fields, ocular pathology causing the low vision, and types of LVAP advised. The primary outcome was to analyze the type of LVAP prescribed in different age groups, and the secondary outcome was the acceptance rate of LVAP.
RESULTS
We analyzed the results of 8309 patients, out of which 2844 (34%. 2) were <15 years of age, 2425 (29.5%) were between 16-40 years, and 3013 (36.3%) were above 40 years. A total of 5522 (66.4%) had best-corrected visual acuity (BCVA) ranging from 6/18-3/60, and 2796 (33.6%) had BCVA from 3/60-No PL. Approximately 38% improved with LVAPs. The most common etiology was retinitis pigmentosa in 1545 (18.6%) patients, followed by congenital nystagmus in 1482 (17.8%), and the least was albinism 383 (4.6%). Maximum prescribed and accepted LVAP were hand and stand magnifiers among 1017 (44.3%) and 512 (52.6%) patients, respectively.
CONCLUSION
Products that are easy to use, require lesser adaptability, are cheap, and require lower maintenance have maximum acceptance rates. We suggest that great emphasis should be laid on training, education, and guidance for low vision rehabilitation centers.
PubMed: 36968774
DOI: 10.4103/sjopt.sjopt_253_21 -
International Journal of Ophthalmology 2023
PubMed: 36935786
DOI: 10.18240/ijo.2023.03.23 -
Oxford Medical Case Reports Feb 2023Hermansky-Pudlak syndrome (HPS) is a rare multisystem disorder inherited in an autosomal recessive manner. Its prevalence is 1 in 500 000 to 1 000 000 people...
Hermansky-Pudlak syndrome (HPS) is a rare multisystem disorder inherited in an autosomal recessive manner. Its prevalence is 1 in 500 000 to 1 000 000 people worldwide. The cause of this disorder is genetic mutations that lead to defective organelles of lysosomes. In this report, a 49-year-old man is introduced who was referred to the medical center with ocular albinism and recently exacerbated shortness of breath. Imaging showed peripheral reticular opacities, ground-glass opacities of the lungs with subpleural sparing in some regions, and thickening of bronchovascular bundles, which were all in favor of non-specific interstitial pneumonia. This imaging pattern is an unusual finding in a patient with HPS.
PubMed: 36860960
DOI: 10.1093/omcr/omad001 -
Journal of Neurochemistry Apr 2023Dopamine (DA) is involved in neurological and physiological functions such as motor control. L-3,4-dihydroxyphenylalanine (L-DOPA), a precursor of DA, is conventionally...
Coupling between GPR143 and dopamine D2 receptor is required for selective potentiation of dopamine D2 receptor function by L-3,4-dihydroxyphenylalanine in the dorsal striatum.
Dopamine (DA) is involved in neurological and physiological functions such as motor control. L-3,4-dihydroxyphenylalanine (L-DOPA), a precursor of DA, is conventionally believed to be an inert amino acid precursor of DA, and its major therapeutic effects in Parkinson's disease (PD) are mediated through its conversion to DA. On the contrary, accumulating evidence suggests that L-DOPA itself is a neurotransmitter. We here show that L-DOPA potentiates DA D2 receptor (DRD2) signaling through GPR143, the gene product of X-linked ocular albinism 1, a G-protein-coupled receptor for L-DOPA. In Gpr143-gene-deficient (Gpr143 ) mice, quinpirole, a DRD2/DRD3 agonist, -induced hypolocomotion was attenuated compared to wild-type (WT) mice. Administration of non-effective dose of L-DOPA methyl ester augmented the quinpirole-induced hypolocomotion in WT mice but not in Gpr143 mice. In cells co-expressing GPR143 and DRD2, L-DOPA enhanced the interaction between GPR143 and DRD2 and augmented quinpirole-induced decrease in cAMP levels. This augmentation by L-DOPA was not observed in cells co-expressing GPR143 and DRD1 or DRD3. Chimeric analysis in which the domain of GPR143 was replaced with GPR37 revealed that GPR143 interacted with DRD2 at the fifth transmembrane domain. Intracerebroventricular administration of a peptide that disrupted the interaction mitigated quinpirole-induced behavioral changes in WT mice but not in Gpr143 mice. These findings provide evidence that coupling between GPR143 and DRD2 is required for selective DRD2 modulation by L-DOPA in the dorsal striatum.
Topics: Animals; Mice; Corpus Striatum; Dopamine; Levodopa; Parkinson Disease; Quinpirole; Receptors, Dopamine D1; Receptors, Dopamine D2; Receptors, G-Protein-Coupled
PubMed: 36807226
DOI: 10.1111/jnc.15789 -
Genes Jan 2023The diagnostic yield of genetic testing for ocular/oculocutaneous albinism (OA/OCA) in a diverse pediatric population in the United States (U.S.) is unclear. Phenotypes...
The diagnostic yield of genetic testing for ocular/oculocutaneous albinism (OA/OCA) in a diverse pediatric population in the United States (U.S.) is unclear. Phenotypes of 53 patients who presented between 2006-2022 with OA/OCA were retrospectively correlated with genetic testing results. Genetic diagnostic yield was defined as detection of pathogenic/likely pathogenic variant(s) matching the anticipated inheritance for that gene-disease relationship. Variant reclassifications of those with variants of uncertain significance (VUS) and without positive diagnostic yield were completed. Overall initial genetic diagnostic yield of OA/OCA was 66%. There was no significant difference ( = 0.59) between race and ethnicities (Black (78%), White (59%), Hispanic/Latino (64%)); however, the diagnostic yield of OA (33%) was significantly lower ( = 0.007) than OCA (76%). Causative variants in (28%) and (20%) were most common. Further, Hermansky-Pudlak syndrome variants were identified in 9% of patients. Re-classification of VUS in non-diagnostic cases resulted in genetic diagnoses for 29% of individuals and increased overall diagnostic yield to 70% of all subjects. There is a high diagnostic yield of genetic testing of patients overall with OA/OCA in a diverse U.S. based pediatric population. Presence or absence of cutaneous involvement of albinism significantly affects genetic diagnostic yield.
Topics: Child; Humans; Retrospective Studies; Mutation; Membrane Transport Proteins; Genetic Testing; Albinism, Ocular; Hermanski-Pudlak Syndrome
PubMed: 36672876
DOI: 10.3390/genes14010135 -
Neuron Jan 2023Visual impairments in albinism result from decreased ipsilateral retinal projections. In this issue of Neuron, Slavi, Balasubramanian, and colleagues demonstrate how low...
Visual impairments in albinism result from decreased ipsilateral retinal projections. In this issue of Neuron, Slavi, Balasubramanian, and colleagues demonstrate how low CyclinD2 in the ciliary marginal zone perturbs generation of ipsilaterally projecting RGCs and that restoring CyclinD2 improves vision in albino mice.
Topics: Animals; Mice; Retinal Ganglion Cells; Retina; Albinism; Vision, Ocular; Visual Pathways
PubMed: 36603550
DOI: 10.1016/j.neuron.2022.12.017 -
Genes Nov 2022Albinism is a genetic disorder, present worldwide, caused by mutations in genes affecting melanin production or transport in the skin, hair and eyes. To date, mutations...
Albinism is a genetic disorder, present worldwide, caused by mutations in genes affecting melanin production or transport in the skin, hair and eyes. To date, mutations in at least 20 different genes have been identified. Oculo-cutaneous Albinism type IV (OCA4) is the most frequent form in Asia but has been reported in all populations, including Europeans. Little is known about the genotype-phenotype correlation. We identified two main phenotypes via the analysis of 30 OCA4 patients with a molecularly proven diagnosis. The first, found in 20 patients, is clinically indistinguishable from the classical OCA1 phenotype. The genotype-to-phenotype correlation suggests that this phenotype is associated with homozygous or compound heterozygous nonsense or deletion variants with frameshift leading to translation interruption in the gene. The second phenotype, found in 10 patients, is characterized by very mild hypopigmentation of the hair (light brown or even dark hair) and skin that is similar to the general population. In this group, visual acuity is variable, but it can be subnormal, foveal hypoplasia can be low grade or even normal, and nystagmus may be lacking. These mild to moderate phenotypes are associated with at least one missense mutation in .
Topics: Humans; Piebaldism; Mutation; Mutation, Missense; Phenotype; Genotype
PubMed: 36553465
DOI: 10.3390/genes13122198 -
Cureus Oct 2022Albinism is a group of heritable illnesses defined by a lack or loss of melanin in tissues originating from the ectoderm (most notably the skin, hair, and eyes). The...
Albinism is a group of heritable illnesses defined by a lack or loss of melanin in tissues originating from the ectoderm (most notably the skin, hair, and eyes). The most common kind of albinism is oculocutaneous albinism (OCA). Clinical evidence of less pigmentation of the hair and skin, as well as the characteristic ocular symptoms, are used to diagnose OCA. Nystagmus is one of the impacts of albinism on the eyes. Nystagmus is a term for involuntary ocular movements that are usually conjugate and rhythmic. Almost always, vertigo, dizziness, and loss of balance occur when nystagmus is accompanied by a condition of the inner ear's vestibular system or the brain. Nystagmus, which is induced by the rotation of an optokinetic drum or the rotation of the body in space, aids in visual maintenance. This case report describes the case of a 10-year-old male child with nystagmus associated with albinism, with typical complaints of dizziness that are scored on a Vanderbilt Pediatric Dizziness Handicap Inventory for Patient Caregivers (DHI-PC). Vestibular rehabilitation for nystagmus aids gaze stabilization, ocular muscle strength improvement, and vestibular function maintenance. The patient recovered with well-planned vestibular rehabilitation, which included gaze stability exercises, Cawthorne-Cooksey exercises, habituation exercises, eyeball resistance exercises, eye-hand coordination exercises, and parent education and home exercise programs.
PubMed: 36407240
DOI: 10.7759/cureus.30452