Typical presentation of autosomal recessive oculocutaneous albinism in two siblings

oc000249 10.3205/oc000249 urn:nbn:de:0183-oc0002497 Case Report Typical presentation of autosomal recessive oculocutaneous albinism in two siblings Nishant Nishant Prateek P

Department of Ophthalmology, All India Institute of Medical Sciences, Patna, India

author Aftab Aftab Naila N

Department of Ophthalmology, All India Institute of Medical Sciences, Patna, India

author Saha Saha Bhawesh B

Department of Ophthalmology, All India Institute of Medical Sciences, Patna, India

author Raj Raj Amit A

Department of Ophthalmology, AIIMS OPD Building, Room No. 447, Phulwarisharif, Patna 801507, Bihar, India, Phone: +91 9646741005Department of Ophthalmology, All India Institute of Medical Sciences, Patna, India

dramitraj@aiimspatna.org author German Medical Science GMS Publishing House

Düsseldorf

610 fovea centralis hypomelanosis iris low vision melanin 20250410 engl This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). 2193-1496 15 GMS Ophthalmology Cases GMS Ophthalmol Cases 01 Objective: We report the case history and clinical findings in two siblings, a 13-year-old male and a 10-year-old female, who presented with complaints of poor vision since childhood. Both children had blonde hair a</PlainText></TextGroup>nd depigmented skin.</Pgraph><Pgraph><Mark1>Methods:</Mark1> Ocular examination revealed white eyebrows, white eyelashes, diminished vision in all eyes, hypochromic irides and pendular nystagmus. On dilated fundus examination, hypopigmented fundi with conspicuously visible choroidal vessels were noted. No foveolar reflex could be discerned and spectral domain optical coherence tomography (SD-OCT) of the macula showed an absence of the foveal pit in all four eyes. On pedigree charting the subjects were the 2<Superscript>nd</Superscript> and 3<Superscript>rd</Superscript> offspring of a non-consanguineous married couple. One of the mother’s siblings and one of the grandmother’s siblings also had a similar disorder.</Pgraph><Pgraph><Mark1>Results:</Mark1> The poor definition of the foveal pit at the centre of the macula, i.e. foveal hypoplasia, accounted for poor visual acuity and nystagmus. Both cases had no syndromic associations. Spectacle correction was prescribed to both children, and low-vision aids and sun protection advised.</Pgraph><Pgraph><Mark1>Conclusion:</Mark1> Oculocutaneous albinism (OCA) represents a range of inherited, congenital disorders of hypomelanosis, involving the skin, hai<TextGroup><PlainText>r, a</PlainText></TextGroup>nd eyes with an estimated prevalence of 1 in 17,000 cases. Affected children suffer severe visual disability while early identification may potentially mitigate it, hence there is need to sensitize primary care practitioners regarding the general symptoms of OCA.</Pgraph></Abstract> <TextBlock name="Introduction" linked="yes"> <MainHeadline>Introduction</MainHeadline><Pgraph>Absence of melanin pigmentation results in albinism which is classically characterised in two groups according to the distribution of the hypomelanosis – oculocutaneous albinism (OCA) and ocular albinism. Non-syndromic OCA represents a range of inherited, congenital disorders of hypomelanosis, involving the skin, hair and eyes, with an estimated prevalence of 1 in 17,000 to 1 in 20,000 <TextLink reference="1"></TextLink>, <TextLink reference="2"></TextLink>, <TextLink reference="3"></TextLink>. There are at least four main types and four minor types of non-syndromic albinism, differing in the genes mutated and in few clinical features <TextLink reference="4"></TextLink>. Here, we exhibit the typical presentation of OCA in two siblings.</Pgraph></TextBlock> <TextBlock name="Case description" linked="yes"> <MainHeadline>Case description</MainHeadline><Pgraph>Two Asian Indian siblings – a 13-year-old male (sibling 1, Figure 1A <ImgLink imgNo="1" imgType="figure" />) and a 10-year-old female (sibling 2, Figure 1B <ImgLink imgNo="1" imgType="figure" />) – presented with complaints of poor vision in both eyes since early childhood. There was no history of use of spectacles. Presenting uncorrected visual acuity was poorer than 6/60 in both eyes (Table 1 <ImgLink imgNo="1" imgType="table" />). On examination, both children had blonde hair, eyebrows, and eyelashes, depigmented skin, as well as pendular nystagmus. The boy had alternating exotropia of 15 degrees.</Pgraph><Pgraph>Anterior segment examination of both children showed hypochromic irides with transillumination defects in both eyes (Figure 2 <ImgLink imgNo="2" imgType="figure" />). The fundi were hypopigmented with conspicuous choroidal vessels and no foveolar reflex (F<TextGroup><PlainText>igure 3 </PlainText></TextGroup><ImgLink imgNo="3" imgType="figure" />).</Pgraph><Pgraph>Stereoacuity testing and cycloplegic retinoscopy were done followed by post-mydriatic test. The result<TextGroup><PlainText>s are s</PlainText></TextGroup>ummarised in Table 1 <ImgLink imgNo="1" imgType="table" />.</Pgraph><Pgraph>Spectral domain optical coherence tomography of the macula of both children showed absence of foveal pit suggestive of foveal hypoplasia in both eyes (Figure 4 <ImgLink imgNo="4" imgType="figure" />). </Pgraph><Pgraph>The subjects were the 2<Superscript>nd</Superscript> and 3<Superscript>rd</Superscript> offspring of a non-co<TextGroup><PlainText>nsanguineo</PlainText></TextGroup>us married couple. One each of the mother’s siblings and paternal grandmother’s siblings also had a similar disorder. A pedigree chart was traced (<TextGroup><PlainText>Figure 5 </PlainText></TextGroup><ImgLink imgNo="5" imgType="figure" />). The children were referred to a paediatrician for systemic examination and investigations, which showed no internal syndromic associations of the ocular conditi<TextGroup><PlainText>on of the p</PlainText></TextGroup>robands. The eldest sibling did not have any ophthalmologic or internal clinical signs.</Pgraph><Pgraph>Spectacle correction was prescribed to both children along with low-vision aids in the form of magnifying glasses. Ultraviolet-blocking photochromatic lenses or powered sunglasses were requested and skin protection advised. Guarded visual prognosis was explained to the parents. Surgical correction of strabismus/nystagmus was discussed with the parents but they declined consent. They were asked to follow up 6-monthly. Genetic counselling was also done. Genetic testing could not be performed due to non-availability of facility for the same in the institution or nearby, as well as financial constraints.</Pgraph></TextBlock> <TextBlock name="Discussion" linked="yes"> <MainHeadline>Discussion</MainHeadline><Pgraph>Our patients exhibit typical features of non-syndromic OCA <TextLink reference="1"></TextLink>, <TextLink reference="5"></TextLink>. OCA is characterized by the systemic findings of hypopigmented skin, hair, eyelashes and eyebrows in addition to the ocular findings. The latter range from nystagmus which is usually pendular and horizontal, poor visual acuity (6/60 or less), loss of stereopsis, intense photophobia, strabismus, large angle kappa, hypochromatic irides with transillumination defects giving the appearance of light blue to almost pink eyes, decreased pigmentation of the retinal pigment epithelium, to the ab-sence or poor definition of foveal pit <TextLink reference="1"></TextLink>, <TextLink reference="3"></TextLink>. Abnormal course of retinal vessels along optic disc is often noted, consisting of an initial nasal deflection followed by an abrupt divergence and reversal of direction to form the temporal vascular arcades <TextLink reference="6"></TextLink>.</Pgraph><Pgraph>All types of OCA are inherited as autosomal recessive disorders. Parents of an affected child are obligate carriers, and offspring of an affected person are obligate carriers. Recurrence risk for another affected child is 25%; in our case, the siblings are consecutive children. Carriers are asymptomatic. Healthy siblings are at 67% risk of being carriers; hence genetic counselling was done for the eldest sibling as well <TextLink reference="1"></TextLink>. In most cases, there <TextGroup><PlainText>is no</PlainText></TextGroup> previous family history of albinism. In our case, we were able to trace a detailed pedigree chart and determi<TextGroup><PlainText>ne th</PlainText></TextGroup>at there was no history of consanguinity. Persons with OCA have normal fertility, and consanguineous marriages can be detrimental as they could propagate the disorder <TextGroup><PlainText>to the</PlainText></TextGroup> next generation. We could not perform a genetic analysis for our patients due to lack of accessible genetic testing facilities as well as financial constraints. This is a limitation of the current case report. It has been shown in an Indian study that genetic testing is helpful in informed decision-making for participating carrier families <TextLink reference="7"></TextLink>. </Pgraph><Pgraph>As regards the management and prognosis of patien<TextGroup><PlainText>ts o</PlainText></TextGroup>f OCA, refractive correction and visual aids shoul<TextGroup><PlainText>d be p</PlainText></TextGroup>rovided to such patients, especially children at schools in forms of high contrast written material, large type textbooks, optical devices such as magnifiers, large monitors, computer software and smartphone-based assistive apps for the visually impaired <TextLink reference="8"></TextLink>. Protection from ultraviolet radiation is also necessary as they have a higher tendency to develop cutaneous malignancies. OCA patients have a normal lifespan with no increase in risk of medical problems as compared to general population except for skin malignancies, which require regular check-ups. D<TextGroup><PlainText>evelop</PlainText></TextGroup>ment and intelligence are normal, and well-re<TextGroup><PlainText>habilitat</PlainText></TextGroup>ed children are able to lead otherwise healthy and productive lives.</Pgraph></TextBlock> <TextBlock name="Conclusion" linked="yes"> <MainHeadline>Conclusion</MainHeadline><Pgraph>This report thus represents a typical presentation of oculo-cutaneous albinism in two siblings. Genetic counselling is essential for promoting informed choices, adaptati<TextGroup><PlainText>on t</PlainText></TextGroup>o individual risks and assessing disease occurrence in the family. Affected children suffer severe visual disability while early identification may potentially mitigate it, hence there is a need to sensitize primary care practitioners regarding general symptoms of OCA.</Pgraph></TextBlock> <TextBlock name="Notes" linked="yes"> <MainHeadline>Notes</MainHeadline><SubHeadline>Patient consent</SubHeadline><Pgraph>Patient consent to publish this case report with full face photographs and ocular imaging was obtained.</Pgraph><SubHeadline>Competing interests</SubHeadline><Pgraph>The authors declare that they have no competing interests.</Pgraph></TextBlock> <References linked="yes"> <Reference refNo="1"> <RefAuthor>Grønskov K</RefAuthor> <RefAuthor>Ek J</RefAuthor> <RefAuthor>Brondum-Nielsen K</RefAuthor> <RefTitle>Oculocutaneous albinism</RefTitle> <RefYear>2007</RefYear> <RefJournal>Orphanet J Rare Dis</RefJournal> <RefPage>43</RefPage> <RefTotal>Grønskov K, Ek J, Brondum-Nielsen K. Oculocutaneous albinism. Orphanet J Rare Dis. 2007 Nov;2:43. 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DOI: 10.1080/10400435.2020.1839144</RefTotal> <RefLink>https://doi.org/10.1080/10400435.2020.1839144</RefLink> </Reference> </References> <Media> <Tables> <Table format="png"> <MediaNo>1</MediaNo> <MediaID>1</MediaID> <Caption><Pgraph><Mark1>Table 1: Visual acuity, refraction and stereoacuity tests of our subjects</Mark1></Pgraph></Caption> </Table> <NoOfTables>1</NoOfTables> </Tables> <Figures> <Figure width="527" height="380" format="png"> <MediaNo>1</MediaNo> <MediaID>1</MediaID> <Caption><Pgraph><Mark1>Figure 1: Full face images of sibling 1 (A) and sibling 2 (B), respectively</Mark1></Pgraph></Caption> </Figure> <Figure width="846" height="325" format="png"> <MediaNo>2</MediaNo> <MediaID>2</MediaID> <Caption><Pgraph><Mark1>Figure 2: Anterior segment photographs showing hypochromic irides in diffuse illumination, and iris transillumination</Mark1></Pgraph></Caption> </Figure> <Figure width="672" height="465" format="png"> <MediaNo>3</MediaNo> <MediaID>3</MediaID> <Caption><Pgraph><Mark1>Figure 3: Fundus photographs showing hypopigmented fundi with conspicuous choroidal vessels</Mark1></Pgraph></Caption> </Figure> <Figure width="873" height="390" format="png"> <MediaNo>4</MediaNo> <MediaID>4</MediaID> <Caption><Pgraph><Mark1>Figure 4: Spectral domain optical coherence tomography (horizontal line scans) through the approximate position of the fovea showing no foveal dip in any of the eyes</Mark1></Pgraph></Caption> </Figure> <Figure width="753" height="475" format="png"> <MediaNo>5</MediaNo> <MediaID>5</MediaID> <Caption><Pgraph><Mark1>Figure 5: Pedigree chart of 3 generations showing the index cases in generation III, with one each of the mother’s siblings and paternal grandmother’s siblings also affected</Mark1></Pgraph></Caption> </Figure> <NoOfPictures>5</NoOfPictures> </Figures> <InlineFigures> <NoOfPictures>0</NoOfPictures> </InlineFigures> <Attachments> <NoOfAttachments>0</NoOfAttachments> </Attachments> </Media> </OrigData> </GmsArticle>