Close
New

Medscape is available in 5 Language Editions – Choose your Edition here.

 

Dermatologic Manifestations of Albinism Clinical Presentation

  • Author: Raymond E Boissy, PhD; Chief Editor: William D James, MD  more...
 
Updated: Jul 21, 2016
 

History

The characteristic hypopigmentation of albinism is apparent at birth. An increase in the pigmentation of the skin and/or the hair may occur with age, especially in individuals who are mildly affected specifically with the non–oculocutaneous albinism type 1 subtypes.

In Chediak-Higashi syndrome, respiratory infections can occur within a few days of birth. Recurrent infections and bleeding diathesis increase with the age of the patient with Chediak-Higashi syndrome. The accelerated phase of Chediak-Higashi syndrome generally manifests by the first decade of life.[5, 6]

In Hermansky-Pudlak syndrome, the bleeding diathesis can occur within a few days of birth generally during circumcision. Throughout life, patients with Hermansky-Pudlak syndrome experience mild-to-moderate bleeding events, including bruising, epistaxis, gingival bleeding, prolonged bleeding during menstruation or after tooth extraction, postpartum hemorrhage, and bleeding colitis. The respiratory system is the primary organ system affected. Restrictive lung disease usually progresses slowly for the first few decades of life and then advances rapidly. The occurrence and the extent of other organ system dysfunctions are variable.

In Griscelli syndrome, the immunodeficiency or neurological defects can occur shortly after birth.

Next

Physical

Oculocutaneous albinism type 1 primarily manifests with complete absence of pigment in the skin, the hair, and the eyes, and this category is termed oculocutaneous albinism type 1A.[7] However, some patients can present with moderate pigmentation in these tissues (termed oculocutaneous albinism type 1B) or pigment in hair follicles of the cooler areas of the body, such as the arms and the legs (termed oculocutaneous albinism type 1TS, ie, temperature sensitive). All forms of oculocutaneous albinism type 1 also present with photophobia, moderate-to-severe reduced visual acuity, and nystagmus. The latter two ocular dysfunctions result from a misrouting of the optic fibers from the retina to the visual cortex of the brain.

Oculocutaneous albinism type 2 does not present with complete absence of pigment but rather manifests with a minimal-to-moderate amount of pigment remaining in the skin, the hair, and the eyes. Many patients with oculocutaneous albinism type 2 can develop pigmented freckles, lentigines, and/or nevi with age. The ocular presentations are similar to those in oculocutaneous albinism type 1.

Oculocutaneous albinism type 3 manifests with minimal pigment reduction in the skin, the hair, and the eyes. This form of albinism was previously referred to as Rufous albinism and possibly Brown albinism. Hair coloration of individuals with oculocutaneous albinism type 3 generally has a yellow or reddish hue. The reduction of cutaneous and ocular pigmentation may only be apparent in comparison with the complexion coloration of family members. The ocular presentations are similar to those in oculocutaneous albinism type 1, but they are not as severe.

Oculocutaneous albinism types 4, 5, 6, and 7 manifest with a phenotype resembling oculocutaneous albinism type 2.[8, 9]

Ocular albinism manifests with ocular depigmentation and iris translucency. In addition, patients with ocular albinism present with congenital motor nystagmus that may be accompanied by reduced visual acuity, refractive errors, fundus hypopigmentation, lack of foveal reflex, and strabismus. Cutaneous depigmentation is not apparent.

Chediak-Higashi syndrome manifests with moderate-to-complete absence of pigment in the skin, the hair, and the eyes. The hypopigmentation of the hair in Chediak-Higashi syndrome generally has a distinct silvery, metallic sheen. Respiratory tract infections frequently occur shortly after birth.

Hermansky-Pudlak syndrome manifests with a variable amount of depigmentation in the skin, the hair, and the eyes. Ophthalmic findings vary.

Griscelli syndrome manifests with a mild form of albinism (ie, pale skin). Distinctive in Griscelli syndrome is the presentation of silvery gray hair at birth.

Previous
Next

Causes

The causes of these diseases are mutations in specific genes.

Oculocutaneous albinism type 1 results from mutations in the tyrosinase gene, which maps to band 11q14-3 and is inherited as an autosomal recessive trait. The tyrosinase gene encodes an enzyme that initiates the synthesis of melanin using the substrate tyrosine. Specifically, tyrosinase hydroxylates tyrosine to dihydroxyphenylalanine (DOPA) and subsequently dehydroxylates DOPA to DOPA-oxidase. More than 70 mutations have been identified in tyrosinase that result in the dysfunction or lack of synthesis of this enzyme. Most patients with oculocutaneous albinism type 1 have compound heterozygosity for mutations in the tyrosinase gene.[10, 11, 12]

Oculocutaneous albinism type 2 results from mutation in the P gene, which maps to band 15q12 and is inherited as an autosomal recessive trait. The P gene encodes a 110-kd protein with 12 putative transmembrane domains localized to the limiting membrane of the pigment granule (ie, melanosome). The function of the P protein in melanin synthesis has yet to be determined.[11, 13]

Oculocutaneous albinism type 3 results from mutation in the tyrosinase-related protein-1 (Tyrp1) gene, which maps to band 9p23 and is inherited as an autosomal recessive trait.[14] The Tyrp1 gene encodes a protein that has been shown to have a dihydroxyindole carboxylic acid (DHICA) oxidase activity in the murine system. DHICA oxidase is a catalytic step downstream from tyrosinase in the biosynthesis of melanin from tyrosine. The function of Tyrp1 in human melanogenesis may be involved as (1) an ionic transporter, (2) a chaperone, and/or (3) a stabilizer of the melanosome complex.[11]

Oculocutaneous albinism type 4 results from mutations in the SLC45A2 gene, formerly called the membrane-associated transporter protein (MATP) gene, which maps to band 5p13.3 and is inherited as an autosomal recessive trait. The SLC45A2 gene encodes a 58-kd protein with 12 predicted transmembrane domains. The function of MATP in melanogenesis is presently unknown.[11, 12, 13]

Oculocutaneous albinism type 5 results from mutations in an unknown gene, which maps to band 4q24 and is inherited as an autosomal recessive trait. The protein and its function is unknown.[9]

Oculocutaneous albinism type 6 results from mutations in the SLC24A5 gene, which maps to band 15q21.1 and is inherited as an autosomal recessive trait. The SLC45A5 gene encoded an uncharacterized membrane-associated transport protein and its function is unknown.[9]

Oculocutaneous albinism type 7 results from mutations in an unknown gene, which maps to band 10q22.2-3 and is inherited as an autosomal recessive trait. The protein is being provisionally labeled as C10orf11 and its function is unknown.[9]

Ocular albinism results from mutation in a gene on the X chromosome, which maps to band Xp22.3-22.2 and is inherited as an X-linked recessive trait. The function of the ocular albinism gene product is unknown.[15]

Chediak-Higashi syndrome results from mutation in the LYST gene, which maps to band 1q42-43 and is inherited as an autosomal recessive trait. The LYST gene encodes a large 429-kd protein that putatively functions in the translocation of material from the Golgi apparatus to target sites in affected cells. As a result, the synthesis of melanosomes by the melanocyte, of delta granules by the platelet, and of lysosomes by some of the leukocytes (ie, neutrophils and natural killer lymphocytes) is impaired.[16]

Hermansky-Pudlak syndrome is inherited as an autosomal recessive trait and exists with loci heterogeneity. The initial form of Hermansky-Pudlak syndrome identified, termed Hermansky-Pudlak syndrome type 1, results from a gene that maps to band 10q23.1-23.3. To date, 8 genetically distinct forms of Hermansky-Pudlak syndrome have been identified in the human population (see Hermansky-Pudlak syndrome). Most of the Hermansky-Pudlak syndrome gene products combine to form several complexes that facilitate the trafficking of molecules from the Golgi to target organelles.[17]

Griscelli syndrome is inherited as an autosomal recessive trait. Two primary genetic variants are known. One results from mutations in the RAB27A gene located at band 15q21 that encodes the GTP-binding protein Rab27a. The other results from mutations in the MYO5A gene located at band 15q21 that encodes the unconventional myosin motor protein myosin5a. Both gene loci are distinct from each other. In the melanocyte, these 2 gene products, along with a third bridging protein (ie, melanophilin) form a complex that facilitates the translocation of melanosomes along microtubules in the dendrites of the melanocyte and their subsequent capture by actin filaments at the dendritic tips.[18]

Previous
Next

Complications

Complications of oculocutaneous albinism type 1 include photophobia, severe-to-moderate reduced visual acuity, and nystagmus. The ocular complications in oculocutaneous albinism type 2, oculocutaneous albinism type 3, and oculocutaneous albinism type 4 are similar to those in oculocutaneous albinism type 1, but, in oculocutaneous albinism type 3, they are not as severe.

Complications of Chediak-Higashi syndrome include easy bruising, mucosal bleeding, epistaxis and petechiae, recurrent infections primarily involving the respiratory system, and neutropenia. In the accelerated phase, fever; anemia; neutropenia; and, occasionally, thrombocytopenia, hepatosplenomegaly, lymphadenopathy, and jaundice may occur. Neurologic problems in Chediak-Higashi syndrome may include a peripheral and cranial neuropathy, autonomic dysfunction, weakness and sensory deficits, loss of deep tendon reflexes, clumsiness with a wide-based gait, seizures, and decreased motor nerve conduction velocities.

Long-term complications of Hermansky-Pudlak syndrome include pulmonary fibrosis, granulomatous colitis, gingivitis, and kidney failure.

Previous
 
 
Contributor Information and Disclosures
Author

Raymond E Boissy, PhD Director of Basic Science Research, Professor, Departments of Dermatology and Cell Biology, University of Cincinnati College of Medicine

Raymond E Boissy, PhD is a member of the following medical societies: Sigma Xi

Disclosure: Received none from University of Cincinnati for none.

Specialty Editor Board

Richard P Vinson, MD Assistant Clinical Professor, Department of Dermatology, Texas Tech University Health Sciences Center, Paul L Foster School of Medicine; Consulting Staff, Mountain View Dermatology, PA

Richard P Vinson, MD is a member of the following medical societies: American Academy of Dermatology, Texas Medical Association, Association of Military Dermatologists, Texas Dermatological Society

Disclosure: Nothing to disclose.

Van Perry, MD Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas School of Medicine at San Antonio

Van Perry, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

Chief Editor

William D James, MD Paul R Gross Professor of Dermatology, Vice-Chairman, Residency Program Director, Department of Dermatology, University of Pennsylvania School of Medicine

William D James, MD is a member of the following medical societies: American Academy of Dermatology, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

Additional Contributors

Jean Paul Ortonne, MD Chair, Department of Dermatology, Professor, Hospital L'Archet, Nice University, France

Jean Paul Ortonne, MD is a member of the following medical societies: American Academy of Dermatology

Disclosure: Nothing to disclose.

James J Nordlund, MD Professor Emeritus, Department of Dermatology, University of Cincinnati College of Medicine

James J Nordlund, MD is a member of the following medical societies: American Academy of Dermatology, Sigma Xi, Society for Investigative Dermatology

Disclosure: Nothing to disclose.

References
  1. Chiang PW, Spector E, Tsai AC. Oculocutaneous albinism spectrum. Am J Med Genet A. 2009 Jul. 149A(7):1590-1. [Medline].

  2. Dessinioti C, Stratigos AJ, Rigopoulos D, Katsambas AD. A review of genetic disorders of hypopigmentation: lessons learned from the biology of melanocytes. Exp Dermatol. 2009 Sep. 18(9):741-9. [Medline].

  3. Oetting WS, Brilliant MH, King RA. The clinical spectrum of albinism in humans. Mol Med Today. 1996 Aug. 2(8):330-5. [Medline].

  4. Oetting WS, King RA. Molecular basis of albinism: mutations and polymorphisms of pigmentation genes associated with albinism. Hum Mutat. 1999. 13(2):99-115. [Medline].

  5. Pujani M, Agarwal K, Bansal S, Ahmad I, Puri V, Verma D, et al. Chediak-Higashi syndrome - a report of two cases with unusual hyperpigmentation of the face. Turk Patoloji Derg. 2011. 27(3):246-8. [Medline].

  6. Roy A, Kar R, Basu D, Srivani S, Badhe BA. Clinico-hematological profile of Chediak-Higashi syndrome: experience from a tertiary care center in south India. Indian J Pathol Microbiol. 2011 Jul-Sep. 54(3):547-51. [Medline].

  7. Lin YY, Wei AH, He X, Zhou ZY, Lian S, Zhu W. A comprehensive study of oculocutaneous albinism type 1 reveals three previously unidentified alleles on the TYR gene. Eur J Dermatol. 2014 Mar-Apr. 24(2):168-73. [Medline].

  8. Hida T, Okura M, Tanaka T, Yamashita T. A case of oculocutaneous albinism type 4: aberrant expression of SLC45A2 transcript with exon skipping. J Dermatol. 2014 Oct 9. [Medline].

  9. Kamaraj B, Purohit R. Mutational analysis of oculocutaneous albinism: a compact review. Biomed Res Int. 2014. 2014:905472. [Medline].

  10. Ray K, Chaki M, Sengupta M. Tyrosinase and ocular diseases: some novel thoughts on the molecular basis of oculocutaneous albinism type 1. Prog Retin Eye Res. 2007 Jul. 26(4):323-58. [Medline].

  11. Rooryck C, Morice-Picard F, Elcioglu NH, Lacombe D, Taieb A, Arveiler B. Molecular diagnosis of oculocutaneous albinism: new mutations in the OCA1-4 genes and practical aspects. Pigment Cell Melanoma Res. 2008 Oct. 21(5):583-7. [Medline].

  12. Zuhlke C, Criee C, Gemoll T, Schillinger T, Kaesmann-Kellner B. Polymorphisms in the genes for oculocutaneous albinism type 1 and type 4 in the German population. Pigment Cell Res. 2007 Jun. 20(3):225-7. [Medline].

  13. Suzuki T, Tomita Y. Recent advances in genetic analyses of oculocutaneous albinism types 2 and 4. J Dermatol Sci. 2008 Jul. 51(1):1-9. [Medline].

  14. Forshew T, Khaliq S, Tee L, et al. Identification of novel TYR and TYRP1 mutations in oculocutaneous albinism. Clin Genet. 2005 Aug. 68(2):182-4. [Medline].

  15. Hutton SM, Spritz RA. A comprehensive genetic study of autosomal recessive ocular albinism in Caucasian patients. Invest Ophthalmol Vis Sci. 2008 Mar. 49(3):868-72. [Medline].

  16. Kaplan J, De Domenico I, Ward DM. Chediak-Higashi syndrome. Curr Opin Hematol. 2008 Jan. 15(1):22-9. [Medline].

  17. Wei ML. Hermansky-Pudlak syndrome: a disease of protein trafficking and organelle function. Pigment Cell Res. 2006 Feb. 19(1):19-42. [Medline].

  18. Menasche G, Fischer A, de Saint Basile G. Griscelli syndrome types 1 and 2. Am J Hum Genet. 2002 Nov. 71(5):1237-8; author reply 1238. [Medline]. [Full Text].

  19. Minakawa S, Kaneko T, Matsuzaki Y, Akasaka E, Mizukami H, Abe Y, et al. Case of oculocutaneous albinism complicated with squamous cell carcinoma, Bowen's disease and actinic keratosis. J Dermatol. 2014 Sep. 41(9):863-4. [Medline].

  20. Chatterjee K, Rasool F, Chaudhuri A, Chatterjee G, Sehgal VN, Singh N. Basal cell carcinoma, oculo-cutaneous albinism and actinic keratosis in a native Indian. Indian J Dermatol. 2013 Sep. 58(5):377-9. [Medline]. [Full Text].

  21. Carden SM, Boissy RE, Schoettker PJ, Good WV. Albinism: modern molecular diagnosis. Br J Ophthalmol. 1998 Feb. 82(2):189-95. [Medline].

  22. King RA, Hearing VJ, Creel DJ. Albinism. Scriver CR, Beaudet AL, Sly WS, Valle DL, eds. The Metabolic and Molecular Bases of Inherited Disease. 7th ed. New York, NY: McGraw-Hill; 1995. Vol 3: 4353-92.

 
Previous
Next
 
Infant with oculocutaneous albinism type 1 presenting with hypomelanotic skin, white hair, and pink irides and pupils resulting from the dysfunction of tyrosinase in the melanocytes of these tissues and the subsequent lack of melanin synthesis. From Carden et al, Br J Ophthal, 1998, 82:189-195, with permission from BMJ Publishing Group.
Neonate with oculocutaneous albinism type 3 presenting with minimally pigmented skin and light hair coloration resulting from the dysfunction of tyrosinase-related protein-1 in the melanocytes of these tissues and the subsequent reduction in melanin synthesis. The infant's parents are African American. From Carden et al, Br J Ophthal, 1998, 82:189-195, with permission from BMJ Publishing Group.
Infant with Chediak-Higashi syndrome presenting with hypomelanotic skin and white hair with a metallic sheen. From Carden et al, Br J Ophthal, 1998, 82:189-195, with permission from BMJ Publishing Group.
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.