Oculocutaneous albinism (OCA) could be either non-syndromic or syndromic. There are significant challenges in clinically recognizing and differentiating Hermansky-Pudlak syndrome (HPS) from non-syndromic OCA.
In a prospective consecutive case series, 63 patients (less than 18 years old) with a molecular genetic diagnosis of albinism (except OCA1A), Ocular albinism (OA) and Hermansky-Pudlak syndrome seen over a 3-year period were evaluated and analyzed. Hair colour, iris colour was graded, compared and correlated with the degree of fundus pigmentation and foveal development.
A total of 63 patients were evaluated. Forty-five patients had non-syndromic OCA (11 OCA1B, 24 OCA2, 9 OCA4, and 1 OCA6), 5 patients had OA and 13 patients had HPS. All 3 BLOC-related HPS categories were seen (1 with BLOC1, 7 with BLOC-2 and 5 with BLOC-3 related HPS). All patients with OA were hyperopic, had darker fundus pigmentation, but had poor foveal development. All HPS patients had lighter fundus pigmentation. The degree of fundus pigmentation correlated positively with the iris pigmentation and also with the foveal development only in OCA2.
Careful observation of the phenotype by comparison of the skin, hair, iris colour, with the degree of fundus pigmentation and foveal development may help clinically differentiate HPS from OCA patients of Chinese ethnicity even in the absence of any bleeding tendency.

To characterize the genotypic and phenotypic spectrum of foveal hypoplasia (FH).
Multicenter, observational study.
A total of 907 patients with a confirmed molecular diagnosis of albinism, PAX6, SLC38A8, FRMD7, AHR, or achromatopsia from 12 centers in 9 countries (n = 523) or extracted from publicly available datasets from previously reported literature (n = 384).
Individuals with a confirmed molecular diagnosis and availability of foveal OCT scans were identified from 12 centers or from the literature between January 2011 and March 2021. A genetic diagnosis was confirmed by sequence analysis. Grading of FH was derived from OCT scans.
Grade of FH, presence or absence of photoreceptor specialization (PRS+ vs. PRS-), molecular diagnosis, and visual acuity (VA).
The most common genetic etiology for typical FH in our cohort was albinism (67.5%), followed by PAX6 (21.8%), SLC38A8 (6.8%), and FRMD7 (3.5%) variants. AHR variants were rare (0.4%). Atypical FH was seen in 67.4% of achromatopsia cases. Atypical FH in achromatopsia had significantly worse VA than typical FH (P < 0.0001). There was a significant difference in the spectrum of FH grades based on the molecular diagnosis (chi-square = 60.4, P < 0.0001). All SLC38A8 cases were PRS- (P = 0.003), whereas all FRMD7 cases were PRS+ (P < 0.0001). Analysis of albinism subtypes revealed a significant difference in the grade of FH (chi-square = 31.4, P < 0.0001) and VA (P = 0.0003) between oculocutaneous albinism (OCA) compared with ocular albinism (OA) and Hermansky-Pudlak syndrome (HPS). Ocular albinism and HPS demonstrated higher grades of FH and worse VA than OCA. There was a significant difference (P < 0.0001) in VA between FRMD7 variants compared with other diagnoses associated with FH.
We characterized the phenotypic and genotypic spectrum of FH. Atypical FH is associated with a worse prognosis than all other forms of FH. In typical FH, our data suggest that arrested retinal development occurs earlier in SLC38A8, OA, HPS, and AHR variants and later in FRMD7 variants. The defined time period of foveal developmental arrest for OCA and PAX6 variants seems to demonstrate more variability. Our findings provide mechanistic insight into disorders associated with FH and have significant prognostic and diagnostic value.

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, GPR143. 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% (n = 23) were male. Genetic testing using whole genome sequencing (WGS, n = 9) or a targeted gene panel (n = 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 TYR (n = 9), OCA2, (n = 4), HPS1 (n = 1), HPS3 (n = 1), HPS6 (n = 1), and GPR143 (n = 1). Molecular diagnosis of albinism remains challenging due to factors such as missing heritability. Differential diagnoses must include SLC38A8-associated foveal hypoplasia and syndromic forms of albinism.

OBJECTIVE: The presence or absence of functional changes associated with solitary, congenital, hypopigmented lesions of the retinal pigment epithelium (RPE) have been a matter of controversy. This case report describes retinal and functional findings in a young patient with such a lesion.
METHODS: A 10-year-old Hispanic female with a solitary congential hypopigmented spot of the RPE was examined using fundus photography, fluorescein angiography, autofluorescence imaging (AF) and optical coherence tomography (OCT). Functional analyses were performed using the Humphrey 24 - 2 visual field, Goldmann perimetry and the multifocal ERG (mfERG).
RESULTS: A small visual field defect was demonstrated on both Goldmann perimetry (I/ 2e test object) and on Humphrey 24 - 2 visual field testing (significant at the 0.5 % level for pattern deviation). The multifocal ERG response amplitudes were decreased in the corresponding area and increased in implicit time. Autofluorescence imaging showed an absence of fluorescence corresponding to the area of the lesion. OCT findings were indicative of a small amount of subretinal fluid or schisis-like changes overlying the RPE anomaly.
CONCLUSIONS: The results indicate that solitary, albinotic spots of the RPE can be associated with visual field defects and outer retinal deficits; these may be related to impaired RPE function and/or chronic exudative changes.

OBJECTIVE: Autosomal recessive ocular albinism (AROA) is a group of genetic disorders in which reduced pigmentation of the eye is associated with decreased visual acuity, nystagmus, strabismus, and photophobia, although pigmentation of skin and hair is relatively normal. Previous studies have shown that AROA in some cases constitutes a clinically mild presentation of oculocutaneous albinism (OCA), due to mutations in either the TYR (OCA1) or OCA2 (P) genes. The purpose of this study was to characterize the relative prevalence of different genetic forms of AROA, and to characterize a sample repertoire of gene mutations in a large series of Caucasian patients with AROA.
METHODS: Thirty-six unrelated Caucasian patients carrying the clinical diagnosis of AROA were studied by DNA sequence analysis of the four classic OCA genes: TYR, OCA2 (P), TYRP1, and SLC45A2 (MATP), as appropriate. In all patients with no apparent pathologic mutations in these genes, DNA sequence analysis was performed of a candidate OCA gene, SILV, and the two genes most often involved in Hermansky-Pudlak syndrome, HPS1 and HPS4, the most frequent syndromic form of OCA.
RESULTS: TYR gene mutations were identified in 20 (56%) patients, OCA2 mutations in 3 (8%), mutations in both TYR and OCA2 in 2 (6%), and possible TYRP1 mutations in 2 (6%). In at least nine patients, no mutations were found in any of the genes studied. Almost all patients with OCA1-related AROA were compound heterozygous for severe OCA1 mutant alleles and the common R402Q variant.
CONCLUSIONS: Most patients with AROA represent phenotypically mild variants of OCA, well over half of which is OCA1.

We report here a clinical study investigating the main visual problems associated with albinism, with a view to determining the best treatment. We came across 42 cases of albinism during the course of this study, corresponding to a prevalence for albinism of 0.15%. One in ten albinos were of the yellow mutant type and more of the albinos were men than were women (sex ratio 1.21). The maximum visual acuity recorded was 3/10 and 40.47% of the patient had a best visual acuity score no higher than 1/10. Vision was best in the yellow mutants and it improved with age. We found that 33.33% of the albino patients had a squint and 35.71% had torticullis at primary fixation. In contrast to the results of previous studies, the most common ametropia was myopic astigmatism (61.9%). These findings have potential implications for the treatment of visual problems in albinos.

In a national retrospective register study 112 patients with ocular albinism (OA) were identified, including 60 male patients with proven or presumed X-linked ocular albinism (XLOA). Based on the birth year cohorts 1960-1989, an XLOA point prevalence at birth of 1 in 60,000 live-born was calculated. We identified 14 XLOA families in the Danish population, and obtained DNA from affected persons in nine families. Mutation analysis of the OA1 gene demonstrated seven presumed pathogenic mutations in the nine families with XLOA: five single nucleotide substitutions predicting a change of conserved amino acids (G35D, L39R, D78V, W133R and E233K) when compared with the mouse OA1 homologue, one deletion leading to the skipping of exon 2, and one single nucleotide substitution expected to affect the 5\' splice site of intron 2 were found. Subsequent genealogical investigations in the three families harbouring the same mutation disclosed that two of the three pedigrees belonged to the same family. All mutations predict crucial changes in the protein structure. Clinical examination failed to identify any phenotype-genotype pattern except a milder phenotype devoid of iris translucency in the patient with the 5\'splice site mutation of intron 2.

The genetic anomaly in albinism prevents adequate melanin metabolism within the fetal eye cup and stalk. This results in severe disruption of pre- and postnatal retinal development and the condition of abnormal temporal retinal projections. The obligate misrouting of retinal-geniculate-cortical projections in albinism can be detected in the topographical representation across the occiput of the visual evoked potential (VEP). Age-dependent misrouting detection methods are described which yield 100% detection rates with zero false positives across the life span. By combining appropriate state-defined neonatal recording procedures with the albino infant VEP test paradigm, the presence of aberrant optic pathway projections was observed in a 5-day-old full-term infant. Maximum asymmetry was observed within a long-latency window of the response which shifted during the postpartum period to shorter latencies. Longitudinal studies show two specific latency regions of significant VEP asymmetry. The first occurs within 40-70 ms after stimulus onset and remains constant across the age range. The second, more robust, cluster of asymmetry occurs within a longer latency window and shows an age-related shift towards shorter latencies. The decreasing latency of this asymmetry is concomitant with normal maturational changes of the evoked response. These results show that VEP misrouting can be extended to reliable albino diagnosis within the neonatal period and to the assessment of visual maturation.