Albinism, Oculocutaneous, Type VI Clinical CharacteristicsOcular Features: Nystagmus is usually present from birth and visual acuity is in the range of 20/100. There is marked hypopigmentation in the retina and the iris often transilluminates. OCT usually shows foveal flattening consistent with hypoplasia. Most patients experience severe photophobia and many have strabismus. Systemic Features: There is usually complete loss or a severe reduction of melanin in skin, hair, and eyes. Hair color is blond but may become tinged with brown in older individuals. The skin may have pigmented nevi and has a tendency to tan in some patients. GeneticsThis is an autosomal recessive disorder resulting from mutations in SLC24A5 (15q21.1). Pedigree: Autosomal recessiveTreatmentTreatment Options: No effective treatment is available. Visual function can be improved with low vision aids. ReferencesArticle Title: SLC24A5 Mutations are Associated with Non-Syndromic Oculocutaneous Albinism Morice-Picard F, Lasseaux E, Fran?ssois S, Simon D, Rooryck C, Bieth E, Colin E, Bonneau D, Journel H, Walraedt S, Leroy BP, Meire F, Lacombe D, Arveiler B. SLC24A5 Mutations are Associated with Non-Syndromic Oculocutaneous Albinism. J Invest Dermatol. 2013 Aug 28. [Epub ahead of print] PubMed PMID: 23985994. PubMed ID: 23985994 Exome sequencing identifies SLC24A5 as a candidate gene for nonsyndromic oculocutaneous albinism Wei AH, Zang DJ, Zhang Z, Liu XZ, He X, Yang L, Wang Y, Zhou ZY, Zhang MR, Dai LL, Yang XM, Li W. Exome sequencing identifies SLC24A5 as a candidate gene for nonsyndromic oculocutaneous albinism. J Invest Dermatol. 2013 Jul;133(7):1834-40. PubMed PMID: 23364476. PubMed ID: 23364476 Read more about Albinism, Oculocutaneous, Type VI
SLC24A5 Mutations are Associated with Non-Syndromic Oculocutaneous Albinism Morice-Picard F, Lasseaux E, Fran?ssois S, Simon D, Rooryck C, Bieth E, Colin E, Bonneau D, Journel H, Walraedt S, Leroy BP, Meire F, Lacombe D, Arveiler B. SLC24A5 Mutations are Associated with Non-Syndromic Oculocutaneous Albinism. J Invest Dermatol. 2013 Aug 28. [Epub ahead of print] PubMed PMID: 23985994. PubMed ID: 23985994
Exome sequencing identifies SLC24A5 as a candidate gene for nonsyndromic oculocutaneous albinism Wei AH, Zang DJ, Zhang Z, Liu XZ, He X, Yang L, Wang Y, Zhou ZY, Zhang MR, Dai LL, Yang XM, Li W. Exome sequencing identifies SLC24A5 as a candidate gene for nonsyndromic oculocutaneous albinism. J Invest Dermatol. 2013 Jul;133(7):1834-40. PubMed PMID: 23364476. PubMed ID: 23364476
Macular Dystrophy, Fenestrated Type Clinical CharacteristicsOcular Features: The earliest fundus findings consisting of a yellowish refractile sheen (about 1 disc diameter in size) with red fenestrations in the central macula were found in a 4 year old. Changes in macular pigmentation were noted at the age of 16 years. Visual acuity remains normal. By the third decade of life an annular zone of hypopigmentation could be seen around the sheen and this gradually enlarged. The sheen seemed to emanate below the retinal vessels but anterior to the RPE. At the center a ‘bull’s eye’ pattern of hyperpigmentation appeared. By the 6th decade of life paracentral scotomas were present causing some visual disturbance. Fluorescein angiography reveals no abnormalities in the sensory retina or retinal vasculature but an annular zone of window defects around the ‘bull’s eye’ can be seen. The scotopic ERG can be normal while the amplitudes of the photopic ERG may show a mild reduction in amplitude and the EOG light-dark ratio can also be slightly reduced. Mild red-green color deficits can be demonstrated. Systemic Features: No systemic abnormalities have been reported. GeneticsNo locus or mutation has been identified but the transmission pattern is compatible with autosomal dominant inheritance in the two reported families. Pedigree: Autosomal dominantTreatmentTreatment Options: No treatment is available. ReferencesArticle Title: Fenestrated sheen macular dystrophy Sneed SR, Sieving PA. Fenestrated sheen macular dystrophy. Am J Ophthalmol. 1991 Jul 15;112(1):1-7. PubMed ID: 1882912 Fenestrated sheen macular dystrophy. A new autosomal dominant maculopathy O'Donnell FE Jr, Welch RB. Fenestrated sheen macular dystrophy. A new autosomal dominant maculopathy. Arch Ophthalmol. 1979 Jul;97(7):1292-6. PubMed ID: 454265 Read more about Macular Dystrophy, Fenestrated Type
Fenestrated sheen macular dystrophy Sneed SR, Sieving PA. Fenestrated sheen macular dystrophy. Am J Ophthalmol. 1991 Jul 15;112(1):1-7. PubMed ID: 1882912
Fenestrated sheen macular dystrophy. A new autosomal dominant maculopathy O'Donnell FE Jr, Welch RB. Fenestrated sheen macular dystrophy. A new autosomal dominant maculopathy. Arch Ophthalmol. 1979 Jul;97(7):1292-6. PubMed ID: 454265
Alagille Syndrome Clinical CharacteristicsOcular Features: The ocular findings in Alagille syndrome are often of little functional significance but can be sufficient to suggest the diagnosis without further study of the systemic features. Posterior embryotoxon is found in 95% of individuals while iris abnormalities such as ectopic pupils are seen in 45%, abnormal fundus pigmentation is common (hypopigmentation in 57%, diffuse pigment speckling in 33%), and optic disc anomalies have been reported in 76%. One study found that 90% of individuals have optic disk drusen by ultrasonography. The anterior chamber anomalies are considered by some to be characteristic of Axenfeld anomaly. The presence of these ocular findings in children with cholestasis should suggest Alagille syndrome. Ocular examination of the parents can also be helpful in this autosomal dominant disorder as some of the same changes are present in one parent in more than a third of cases. Systemic Features: A variety of systemic features, some of them serious malformations, occur in Alagille syndrome. Among the most common is a partial intrahepatic biliary atresia leading to cholestasis and jaundice. Skeletal malformations include 'butterfly' vertebrae, shortened digits, short stature, a broad forehead, and a pointed chin. The tip of the nose may appear bulbous. These features have suggested to some that there is a characteristic facial dysmorphology. Vascular malformations are common including aneurysms affecting major vessels, valvular insufficiency, coarctation of the aorta, and stenosis and these are often responsible for the most serious health problems. In fact, vascular events have been reported to be responsible for mortality in 34% of one cohort. Chronic renal insufficiency develops in a minority of patients. This disorder should always be considered in children with cholestasis, especially when accompanied by cystic kidney disease. Brain MRIs may show diffuse or focal hyperintensity of white matter even in the absence of hepatic encephalopathy. GeneticsThis is an autosomal dominant condition secondary to various mutations in the JAG1 gene located on chromosome 20 (20p12). Penetrance is nearly 100% but there is considerable variation in expression. A far less common variant of this disorder, ALGS2 (610205), is caused by a mutation in the NOTCH2 gene (1p13-p11). Pedigree: Autosomal dominantTreatmentTreatment Options: No cure is available but individual organ disease may be treatable. The ocular abnormalities generally do not cause vision difficulties. Reversible of white matter changes has been noted in a single child following liver transplantation. ReferencesArticle Title: Alagille Syndrome: An Overview Jesina D. Alagille Syndrome: An Overview. Neonatal Netw. 2017 Nov 1;36(6):343-347. PubMed ID: 29185945 Anterior Chamber Pathology in Alagille Syndrome Ho DK, Levin AV, Anninger WV, Piccoli DA, Eagle RC Jr. Anterior Chamber Pathology in Alagille Syndrome. Ocul Oncol Pathol. 2016 Oct;2(4):270-275. PubMed ID: 27843908 CT-defined phenotype of pulmonary artery Rodriguez RM, Feinstein JA, Chan FP. CT-defined phenotype of pulmonary arterystenoses in Alagille syndrome. Pediatr Radiol. 2016 Apr 4. [Epub ahead of print]. PubMed ID: 27041277 Reversible diffuse white matter lesion in Alagille syndrome Takenouchi T, Shimozato S, Kosaki K, Momoshima S, Takahashi T. Reversible diffuse white matter lesion in Alagille syndrome. Pediatr Neurol. 2011 Jul;45(1):54-6. PubMed ID: 21723462 Alagille syndrome: clinical and ocular pathognomonic features El-Koofy NM, El-Mahdy R, Fahmy ME, El-Hennawy A, Farag MY, El-Karaksy HM. Alagille syndrome: clinical and ocular pathognomonic features. Eur J Ophthalmol. 2010 Jul 28. pii: 192165A5-8631-4C06-9C47-9AD63688B02A. [Epub ahead of print] PubMed ID: 20677167 Medical management of Alagille syndrome Kamath BM, Loomes KM, Piccoli DA. Medical management of Alagille syndrome. J Pediatr Gastroenterol Nutr. 2010 Jun;50(6):580-6. PubMed ID: 20479679 Vascular anomalies in Alagille syndrome: a significant cause of morbidity and mortality Kamath BM, Spinner NB, Emerick KM, Chudley AE, Booth C, Piccoli DA, Krantz ID. Vascular anomalies in Alagille syndrome: a significant cause of morbidity and mortality. Circulation. 2004 Mar 23;109(11):1354-8. PubMed ID: 14993126 Ocular abnormalities in Alagille syndrome Hingorani M, Nischal KK, Davies A, Bentley C, Vivian A, Baker AJ, Mieli-Vergani G, Bird AC, Aclimandos WA. Ocular abnormalities in Alagille syndrome. Ophthalmology. 1999 Feb;106(2):330-7. PubMed ID: 9951486 Read more about Alagille Syndrome
Alagille Syndrome: An Overview Jesina D. Alagille Syndrome: An Overview. Neonatal Netw. 2017 Nov 1;36(6):343-347. PubMed ID: 29185945
Anterior Chamber Pathology in Alagille Syndrome Ho DK, Levin AV, Anninger WV, Piccoli DA, Eagle RC Jr. Anterior Chamber Pathology in Alagille Syndrome. Ocul Oncol Pathol. 2016 Oct;2(4):270-275. PubMed ID: 27843908
CT-defined phenotype of pulmonary artery Rodriguez RM, Feinstein JA, Chan FP. CT-defined phenotype of pulmonary arterystenoses in Alagille syndrome. Pediatr Radiol. 2016 Apr 4. [Epub ahead of print]. PubMed ID: 27041277
Reversible diffuse white matter lesion in Alagille syndrome Takenouchi T, Shimozato S, Kosaki K, Momoshima S, Takahashi T. Reversible diffuse white matter lesion in Alagille syndrome. Pediatr Neurol. 2011 Jul;45(1):54-6. PubMed ID: 21723462
Alagille syndrome: clinical and ocular pathognomonic features El-Koofy NM, El-Mahdy R, Fahmy ME, El-Hennawy A, Farag MY, El-Karaksy HM. Alagille syndrome: clinical and ocular pathognomonic features. Eur J Ophthalmol. 2010 Jul 28. pii: 192165A5-8631-4C06-9C47-9AD63688B02A. [Epub ahead of print] PubMed ID: 20677167
Medical management of Alagille syndrome Kamath BM, Loomes KM, Piccoli DA. Medical management of Alagille syndrome. J Pediatr Gastroenterol Nutr. 2010 Jun;50(6):580-6. PubMed ID: 20479679
Vascular anomalies in Alagille syndrome: a significant cause of morbidity and mortality Kamath BM, Spinner NB, Emerick KM, Chudley AE, Booth C, Piccoli DA, Krantz ID. Vascular anomalies in Alagille syndrome: a significant cause of morbidity and mortality. Circulation. 2004 Mar 23;109(11):1354-8. PubMed ID: 14993126
Ocular abnormalities in Alagille syndrome Hingorani M, Nischal KK, Davies A, Bentley C, Vivian A, Baker AJ, Mieli-Vergani G, Bird AC, Aclimandos WA. Ocular abnormalities in Alagille syndrome. Ophthalmology. 1999 Feb;106(2):330-7. PubMed ID: 9951486
