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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 -
Neuron Jan 2023In albinism, aberrations in the ipsi-/contralateral retinal ganglion cell (RGC) ratio compromise the functional integrity of the binocular circuit. Here, we focus on the...
In albinism, aberrations in the ipsi-/contralateral retinal ganglion cell (RGC) ratio compromise the functional integrity of the binocular circuit. Here, we focus on the mouse ciliary margin zone (CMZ), a neurogenic niche at the embryonic peripheral retina, to investigate developmental processes regulating RGC neurogenesis and identity acquisition. We found that the mouse ventral CMZ generates predominantly ipsilaterally projecting RGCs, but this output is altered in the albino visual system because of CyclinD2 downregulation and disturbed timing of the cell cycle. Consequently, albino as well as CyclinD2-deficient pigmented mice exhibit diminished ipsilateral retinogeniculate projection and poor depth perception. In albino mice, pharmacological stimulation of calcium channels, known to upregulate CyclinD2 in other cell types, augmented CyclinD2-dependent neurogenesis of ipsilateral RGCs and improved stereopsis. Together, these results implicate CMZ neurogenesis and its regulators as critical for the formation and function of the mammalian binocular circuit.
Topics: Animals; Mice; Albinism; Cell Division; Mammals; Neurogenesis; Retina; Retinal Ganglion Cells; Visual Pathways
PubMed: 36351424
DOI: 10.1016/j.neuron.2022.10.025 -
Transactions of the American... 1996The purpose of this investigation was to study vision in albinism from 3 perspectives: first, to determine the characteristics of grating acuity development in children... (Comparative Study)
Comparative Study
PURPOSE
The purpose of this investigation was to study vision in albinism from 3 perspectives: first, to determine the characteristics of grating acuity development in children with albinism; second, to study the effect of illumination on grating acuity; and third, to define the effect of melanin pigment in the macula on visual acuity.
METHODS
I. Binocular and monocular grating acuity was measured with the acuity card procedure in 40 children with albinism during the first 3 years of life. Recognition acuity was eventually measured in 27 of these patients. Ocular pigment was documented by a previously established method of grading iris transillumination and macular transparency. II. Grating acuity under standard and increased illumination levels was measured in 20 adults with albinism (group I) compared with that in 20 adults with nystagmus due to conditions other than albinism (group II) and 20 adults without ocular abnormalities (group III). Recognition acuity measured with the ETDRS charts was also recorded for each group. III. Best-corrected binocular acuity was measured in 29 patients with albinism who were identified with melanin pigment in their maculas by direct ophthalmoscopy.
RESULTS
I. Both binocular and monocular grating acuity was reduced 2 to 3 octaves below the norm for ages 6 months to 3 years. Limited data available in the first 6 months of life did not show failure of vision to develop. Grating acuity measurements overestimated eventual recognition acuity. Mean recognition acuity was 20/111. A relationship between grating acuity development and presence or absence of ocular pigment was not found. II. Grating acuity was significantly better for groups I and II under the condition of increased illumination (P < .03). For patients with albinism, grating acuity under standard illumination was significantly better than recognition acuity (P < .001). For all groups, grating acuity under increased illumination was significantly better than recognition acuity (P < .01). III. Mean recognition acuity in patients with albinism and melanin pigment in their maculas (20/47) was significantly better than measured recognition acuity in Project I (P < .001). All had foveal hypoplasia, but 8 patients had an incompletely developed annular reflex in the macula, 6 patients showed stereoacuity, and 3 patients had no nystagmus.
CONCLUSIONS
I. Grating acuity development in albinism seems to progress along a curve that is asymptotic to visual development in a normal population. II. Increasing illumination does not reduce grating acuity in patients with albinism. Grating acuity overestimates recognition acuity in these patients. III. Ophthalmoscopic detection of melanin pigment in the macula in patients with albinism is associated with better vision.
Topics: Adolescent; Adult; Albinism, Ocular; Albinism, Oculocutaneous; Child; Child, Preschool; Evoked Potentials, Visual; Female; Fundus Oculi; Humans; Infant; Light; Macula Lutea; Male; Melanins; Middle Aged; Nystagmus, Pathologic; Vision, Binocular; Vision, Ocular; Visual Acuity
PubMed: 8981720
DOI: No ID Found -
Investigative Ophthalmology & Visual... Jan 2022The purpose of this study was to further expand the mutational spectrum of the Foveal Hypoplasia, Optic Nerve Decussation defect, and Anterior segment abnormalities... (Comparative Study)
Comparative Study
PURPOSE
The purpose of this study was to further expand the mutational spectrum of the Foveal Hypoplasia, Optic Nerve Decussation defect, and Anterior segment abnormalities (FHONDA syndrome), to describe the phenotypic spectrum, and to compare it to albinism.
SUBJECTS AND METHODS
We retrospectively collected molecular, ophthalmic, and electrophysiological data of 28 patients molecularly confirmed with FHONDA from the Netherlands (9), Israel (13), France (2), and the United States of America (4). We compared the data to that of 133 Dutch patients with the 3 most common types of albinism in the Netherlands: oculocutaneous albinism type 1 (49), type 2 (41), and ocular albinism (43).
RESULTS
Patients with FHONDA had a total of 15 different mutations in SLC38A8, of which 6 were novel. Excluding missing data, all patients had moderate to severe visual impairment (median visual acuity [VA] = 0.7 logMAR, interquartile range [IQR] = 0.6-0.8), nystagmus (28/28), and grade 4 foveal hypoplasia (17/17). Misrouting was present in all nine tested patients. None of the patients had any signs of hypopigmentation of skin and hair. VA in albinism was better (median = 0.5 logMAR, IQR = 0.3-0.7, P 0.006) and the phenotypes were more variable: 14 of 132 without nystagmus, foveal hypoplasia grades 1 to 4, and misrouting absent in 16 of 74.
CONCLUSIONS
Compared to albinism, the FHONDA syndrome appears to have a more narrow phenotypic spectrum, consisting of nonprogressive moderately to severely reduced VA, nystagmus, severe foveal hypoplasia, and misrouting. The co-occurrence of nystagmus, foveal hypoplasia, and misrouting in the absence of hypopigmentation implies that these abnormalities are not caused by lack of melanin, which has important implications for understanding the pathogenesis of these features.
Topics: Adolescent; Adult; Aged; Albinism, Oculocutaneous; Amino Acid Transport Systems, Neutral; Anterior Eye Segment; Child; Child, Preschool; DNA; DNA Mutational Analysis; Female; Follow-Up Studies; Fovea Centralis; Humans; Infant; Male; Middle Aged; Mutation; Phenotype; Retrospective Studies; Syndrome; Visual Acuity; Young Adult
PubMed: 35029636
DOI: 10.1167/iovs.63.1.19 -
Journal of Neuroscience Research Jan 2019Albinism, typically characterized by decreased melanin synthesis, is associated with significant visual deficits owing to developmental changes during neurosensory... (Review)
Review
Albinism, typically characterized by decreased melanin synthesis, is associated with significant visual deficits owing to developmental changes during neurosensory retina development. All albinism is caused by genetic mutations in a group of diverse genes including enzymes, transporters, G-protein coupled receptor. Interestingly, these genes are not expressed in the neurosensory retina. Further, regardless of cause of albinism, all forms of albinism have the same retinal pathology, the extent of which is variable. In this review, we explore the possibility that this similarity in retinal phenotype is because all forms of albinism funnel through the same final common pathway. There are currently seven known genes linked to the seven forms of ocular cutaneous albinism. These types of albinism are the most common, and result in changes to all pigmented tissues (hair, skin, eyes). We will discuss the incidence and mechanism, where known, to develop a picture as to how the mutations cause albinism. Next, we will examine the one form of albinism which causes tissue-specific pathology, ocular albinism, where the eye exhibits the retinal albinism phenotype despite near normal melanin synthesis. We will discuss a potential way to treat the disease and restore normal retinal development. Finally, we will briefly discuss the possibility that this same pathway may intersect with the most common cause of permanent vision loss in the elderly.
Topics: Albinism, Ocular; Eye Proteins; Humans; Melanins; Membrane Glycoproteins; Mutation; Pigmentation; Retina; Retinal Pigment Epithelium
PubMed: 29761529
DOI: 10.1002/jnr.24246 -
Genes Jun 2022Oculocutaneous albinism (OCA) is an autosomal recessive syndromic and non-syndromic defect with deficient or a complete lack of the melanin pigment. The characteristics... (Review)
Review
Oculocutaneous albinism (OCA) is an autosomal recessive syndromic and non-syndromic defect with deficient or a complete lack of the melanin pigment. The characteristics of OCA appears in skin, hair, and eyes with variable degree of pigmentation. Clinical manifestations of OCA include nystagmus, photophobia, reduced visual acuity, hypo-plastic macula, and iris trans-illumination. There are eight OCA types (OCA1-8) documented with non-syndromic characteristics. Molecular studies identified seven genes linked to the OCA phenotype (, , , , , and ) and one locus (OCA5) in consanguineous and sporadic albinism. The complications of OCA result in skin cancer and variable syndromes such as Hermansky-Pudlak syndrome (HPS) Chediak-Higashi syndrome (CHS). In the Pakistani population, autosomal recessive non-syndromic OCA is common and is associated with a large number of consanguineous families, and mutations in genes of non-syndromic types are reported. This review highlights the updates on the genetic mutation of OCA genes reported from Pakistani families. Several studies reported the genetic mutations in OCA1, OCA2, OCA3, OCA4, and OCA6 albinism in Pakistani families. A locus, OCA5, was also reported from the Pakistani population, but the gene has not been identified. A new type of OCA8 was identified due to the gene mutation, and it is also reviewed here.
Topics: Albinism; Albinism, Oculocutaneous; Carrier Proteins; Humans; Mutation; Pakistan
PubMed: 35741834
DOI: 10.3390/genes13061072 -
Indian Journal of Ophthalmology Jul 2022To study the retinal and choroidal thickness variations on enhanced depth imaging optical coherence tomography scans in ocular albinism (OA) and compare with age-matched... (Observational Study)
Observational Study
PURPOSE
To study the retinal and choroidal thickness variations on enhanced depth imaging optical coherence tomography scans in ocular albinism (OA) and compare with age-matched healthy subjects.
METHODS
This retrospective observational study had 48 eyes of 24 patients diagnosed clinically as OA and age, sex, and axial length-matched control healthy subjects. All patients underwent detailed ophthalmic examination and a single-line horizontal-raster enhanced depth imaging - optical coherence tomography scan (Spectralis, Heidelberg Engineering). Retinal and choroidal thickness was measured, compared, and analyzed between the two groups. Mann-Whitney U test was used for analysis between the two groups. P < 0.05 was considered significant.
RESULTS
The mean age was 28.3 ± 11.6 and 29.9 ± 10.6 years in the OA group and control group, respectively. Spherical equivalents ranged from -8.5D to +10.5D in the OA group and from -8.0D to +10.0D in the control group. The mean axial length between the two groups (P = 0.652) were comparable. The average retinal thickness (272 ± 34.3 vs. 213 ± 13.8 μm; P < 0.001) was greater in the OA group as compared to controls. The mean choroidal thickness (184 ± 78.4 vs. 287 ± 46.4 μm; P < 0.001) was significantly thinner in the OA group.
CONCLUSION
Acquisition of OCT scans in OA can be challenging. This study showed that the subfoveal retinal thickness and choroidal thickness measured across the scans were significantly different in the OA group compared to controls. In the future, more studies are required to evaluate the role of the choroid and its relationship to emmetropization in albinism.
Topics: Adolescent; Adult; Albinism, Ocular; Choroid; Humans; Retina; Retrospective Studies; Tomography, Optical Coherence; Young Adult
PubMed: 35791146
DOI: 10.4103/ijo.IJO_2907_21 -
BMC Medical Informatics and Decision... Jun 2023Reduced or absence of melanin poses physical, social, and psychological challenges to individuals with albinism. Mobile health (mHealth) applications have the potential...
BACKGROUND
Reduced or absence of melanin poses physical, social, and psychological challenges to individuals with albinism. Mobile health (mHealth) applications have the potential to improve the accessibility of information and services while reducing time and costs. This study aimed to develop and evaluate a mHealth application for self-management of albinism.
METHODS
This applied study was conducted in two stages (development and evaluation) in 2022. Initially, the functional requirements were determined, and the conceptual model of the application was then developed using Microsoft Visio 2021. In the second phase, the application was evaluated using the Mobile Application Usability Questionnaire (MAUQ) involving patients with albinism to reflect their views on the usability of the application.
RESULTS
The key capabilities of the application included: reminders, alerts, educational content, useful links, storage and exchange of images of skin lesions, specialist finder, and notifications for albinism-relevant events. Twenty-one users with albinism participated in the usability testing of the application. The users were predominantly satisfied with the application (5.53 ± 1.10; Max: 7.00).
CONCLUSIONS
The findings of this study suggest that the developed mobile application could assist individuals with albinism to effectively manage their condition by considering the users' requirements and services that the application should deliver.
Topics: Humans; Mobile Applications; Self-Management; Albinism; Physical Examination; Telemedicine
PubMed: 37312174
DOI: 10.1186/s12911-023-02202-7 -
Genes Jul 2022Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive syndromic form of albinism, characterized by oculocutaneous albinism (OCA) and other systemic...
Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive syndromic form of albinism, characterized by oculocutaneous albinism (OCA) and other systemic complications. The purpose of this study was to investigate patients with HPS-associated gene mutations and describe associated ocular and extraocular phenotypes. Fifty-four probands clinically diagnosed as albinism were enrolled. Ophthalmic examinations and genetic testing were performed in all subjects. The phenotypic and genetic features were evaluated. HPS-associated gene mutation was identified in four of the patients with albinism phenotype. Clinically, photophobia, and nystagmus was detected in all (4/4) patients, and strabismus was found in one (1/4) patient. Fundus examination revealed fundus hypopigmentation and foveal hypoplasia in all (8/8) eyes. Eight novel causative mutations were detected in these four HPS probands. Five (62.5%, 5/8) of the mutations were nonsense, two of the mutations were missense (25%, 2/8), and one of the mutations was frameshift (12.5%, 1/8). All patients in our study carried compound heterozygous variants, and all these pathogenic variants were identified to be novel, with most (62.5%, 5/8) of the mutations being nonsense. Our results improved the understanding of clinical ocular features, and expanded the spectrum of known variants and the genetic background of HPS.
Topics: Eye; Genetic Testing; Hermanski-Pudlak Syndrome; Humans; Mutation; Phenotype
PubMed: 35886065
DOI: 10.3390/genes13071283 -
Genes Mar 2021Albinism encompasses a group of hereditary disorders characterized by reduced or absent ocular pigment and variable skin and/or hair involvement, with syndromic forms...
Albinism encompasses a group of hereditary disorders characterized by reduced or absent ocular pigment and variable skin and/or hair involvement, with syndromic forms such as Hermansky-Pudlak syndrome and Chédiak-Higashi syndrome. Autosomal recessive oculocutaneous albinism (OCA) is phenotypically and genetically heterogenous (associated with seven genes). X-linked ocular albinism (OA) is associated with only one gene, . We report the clinical and genetic outcomes of 44 patients, from 40 unrelated families of diverse ethnicities, with query albinism presenting to the ocular genetics service at Moorfields Eye Hospital NHS Foundation Trust between November 2017 and October 2019. Thirty-six were children (≤ 16 years) with a median age of 31 months (range 2-186), and eight adults with a median age of 33 years (range 17-39); 52.3% ( = 23) were male. Genetic testing using whole genome sequencing (WGS, = 9) or a targeted gene panel ( = 31) gave an overall diagnostic rate of 42.5% (44.4% (4/9) with WGS and 41.9% (13/31) with panel testing). Seventeen families had confirmed mutations in ( = 9), , ( = 4), ( = 1), ( = 1), ( = 1), and ( = 1). Molecular diagnosis of albinism remains challenging due to factors such as missing heritability. Differential diagnoses must include -associated foveal hypoplasia and syndromic forms of albinism.
Topics: Adolescent; Adult; Albinism, Ocular; Albinism, Oculocutaneous; Child; Child, Preschool; Diagnosis, Differential; Female; Genetic Testing; Humans; Infant; Male; Mutation; Pedigree; Phenotype; Prospective Studies; Whole Genome Sequencing; Young Adult
PubMed: 33808351
DOI: 10.3390/genes12040508