Case Report: a Black and White Twin

Home , Albinism, Melanin

MJ Claas, A Timmermans and HW Bruinse Department of Obstetrics, Wilhelmina Children’s Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands

Apgar scores at 1 and 5 min of 8 and 9 and 10 and 10, respectively. Albinism is an autosomal recessive disorder that is caused by a defective At physical examination, great differences between child I and synthesis of melanin, resulting in a generalized reduction of pigmentation child II were noticed. Child I appeared to have a light brown skin, in the skin, hair and eyes, and leading to an increased risk of skin cancer black curly hair and brown eyes, whereas the second child had a and vision problems. We report a case of a 22-year-old primigravida of striking white skin, red-blond curly hair and blue eyes (Figure 1). Negroid origin who delivered dichorial diamniotic twins: two daughters were An explanation for the great difference in appearance between born with a totally different appearance. The first child had a light brown the two children could be heteropaternity. Wenk et al.1 reported skin, black curly hair and brown eyes, whereas the second had a striking three cases of heteropaternity in a large parentage test database and white skin, red-blond curly hair and blue eyes. Oculocutaneous albinism quoted a frequency of 2.4% for such cases among dizygotic twins (OCA) and heteropaternal superfecundation were considered in the whose parents were involved in paternity suits. James2 estimated the differential diagnosis. Genetic testing confirmed the diagnosis of OCA type 2 incidence of heteropaternal superfecundation to be 1 pair in 400 in the second child. The diagnosis of albinism has clinical implications and twin births for white women in the United States. Reports suggest must be considered when a black and white twin is born. that the frequency of heteropaternity is underestimated, as the Journal of Perinatology (2010) 30, 434–436; doi:10.1038/jp.2009.156 incidence of heteropaternity depends on promiscuity in the 1–4 Keywords: oculocutaneous albinism; black and white twin; population and the extent of performing DNA analyses. heteropaternity Additional medical history has revealed that the mother and the biological father of the twins are of Congolese origin, and that they both have a Negroid appearance. The mother firmly stated not Introduction having had another partner at the time of the conception. The family history of the mother mentions that both her parents are of Albinism is an autosomal recessive disorder that is caused by a Congolese origin, and that her mother, aunt and grandmother defective synthesis of melanin. Albinism is characterized by a were born with a white skin and red-blond curly hair. Her mother generalized reduction of pigment in the skin, hair and eyes. and grandmother had green eyes and her aunt had blue eyes. The worldwide prevalence of albinism is 1 in 20 000 people. On account of this information, albinism in child II became Albinism is present in all races, although an increased prevalence more likely. is found in Negroid races. In Europe, 1 in 70 people is a carrier of Ophthalmologic examination of child II at the age of 1 month the albino gene and 1 in 17 000 to 20 000 people is actually an confirmed a blue iris; no pigment was observed in the fundus and albino. In Africa, 1 in 22 to 35 people carries a gene for albinism the papilla was grayish. These findings correspond to the clinical and 1 in 2000 to 5000 people actually is an albino.2,3 picture of oculocutaneous albinism (OCA). Examination at 3 months of age showed a horizontal nystagmus and the absence of Case following and fixating objects. At 5 months of age, the nystagmus was still present, resulting in head nodding; nevertheless, the child A 22-year-old healthy primigravida of Negroid origin spontaneously had started following objects. At 7 months, a nystagmus increasing conceived a dichorial diamniotic twin (confirmed by pathology in bright light was still present, and it was noted that the color of examination of the placenta). Pregnancy was uneventful until she the iris had changed from blue to green. Visual acuity was tested at was admitted at 40 weeks of gestation with preeclampsia. Induction 9 months and showed no abnormalities. of labor followed, and subsequently a cesarean section was performed because of dystocia. Two daughters were born, with

Correspondence: Dr MJ Claas, Department of Obstetrics, Wilhelmina Children’s Hospital, Discussion University Medical Centre, KE 04.123.1, PO Box 85090, Utrecht 3508 AB, The Netherlands. E-mail: [email protected] Albinism is an autosomal recessive disorder that is caused by a Received 12 August 2009; accepted 27 August 2009 defective synthesis of melanin. In the synthesis of melanin, the Case report: a black and white twin MJ Claas et al 435

The retina is damaged by defective filtration of ultraviolet radiation by the iris, leading to decreased visual acuity (usually in the range 20/60 to 20/400) or even blindness. The vision problems are mainly caused by foveal hypoplasia and misrouting of the optic nerve fibers, because of the absence or reduced presence of melanin. Foveal hypoplasia leads to an inaccurate projection of the image on the macula lutea because of the widespread localization of the cones, resulting in reduced vision and nystagmus that presents from the age of 3 to 4 months.5,6 There is no curative treatment for albinism. Photoprotection, however, can reduce the main complications such as skin cancer and loss of vision. Examples of preventive measures are covering clothing, sunglasses and sunscreen. An annual check-up of the Figure 1 A black and white twin. skin is advised for early diagnosis and treatment of premalignant or malignant skin disorders. Improvement of the vision can be accomplished by means of sunglasses, the use of indirect light and enzyme tyrosinase is of major importance, because it conducts the contrast, and of course optimal dioptry correction. Complaints of first step of the melanin biosynthetic pathway. There are different nystagmus can be treated with contacts or surgical correction of types of OCA. Most relevant are OCA types 1 and 2. Type 1 is called the eye muscles.5,6 the tyrosinase negative form, and is divided into 1A and 1B, The most prevalent skin disorders in albinos are basal cell and these two types result from a mutation of the tyrosinase carcinoma and squamous cell carcinoma, whereas melanoma are gene (TYR gene) on chromosome 11. In type 1A, the TYR gene rare.5 The highest prevalence of squamous cell carcinoma is produces a completely inactive tyrosinase enzyme, and hence no consistently shown in the albino population.7–10 Lookingbill et al.9 melanin is formed in any melanocyte. In type 1B, the TYR gene studied albinos in Tanzania and found actinic keratosis in 91% of produces a partially active tyrosinase enzyme, resulting in a the albino patients of 20 years and older, and in 34% of the diminished synthesis of melanin. In OCA type 2, a mutation in patients who were 30 years and older they diagnosed skin cancer. the OCA 2 or P gene on chromosome 15 is present. The OCA 2 Death from skin cancer resulted from erosion through the eyes, protein produced is important for normal biogenesis of melano- skull or large blood vessels. This occurred with squamous cell somes, and for normal processing and transport of melanosomal carcinoma, whereas the basal cell carcinoma is less aggressive and proteins such as tyrosinase. Owing to the OCA 2 mutation, does not metastasize.5 Aquaron studied 273 patients with OCA with tyrosinase is retained in perinuclear compartments, resulting in a 15-year follow-up, and concluded that the majority of the albinos a diminished synthesis of melanin. As functional tyrosinase is die from skin cancer.10 Albinism is a rare disease, but the increased produced in OCA type 2, it is named the tyrosinase-positive form.5,6 risk of skin cancer and vision problems indicates the importance of OCA types 1 and 2 differ on the bases of genetics and the degree the diagnosis. When a black and white twin is born, one should of skin and hair hypopigmentation and ocular manifestations, consider the diagnosis albinism. with OCA type 1 being more severe. Genetic testing, by demonstration of the mutated TYR or OCA 2 gene in a blood sample, confirms the diagnosis of albinism. Conflict of interest Prenatal diagnosis of albinism is also possible by demonstration of The authors declare no conflict of interest. the mutated tyrosinase gene after amniocentesis or from a fetal skin biopsy.5 The child described in the case was diagnosed with OCA type 2 by means of DNA analysis in a blood sample (direct sequencing Acknowledgments showed an exon 7 deletion in the P gene). However, albinism is We thank the mother of the twin for her consent to publish this case report. merely clinically diagnosed by the patient’s appearance, being characterized by a general reduction of pigment in the skin, hair and eyes. References Exposure of the non- or reduced pigmented skin to sun 1 Wenk RE, Houtz T, Brooks M, Chiafari FA. How frequent is heteropaternal radiation leads to sunburns, pigmented spots and skin cancer. superfecundation? Acta Genet Med Gemellol 1992; 41: 43–47. Ocular manifestations of albinism include photofobia with painful 2 James WH. The incidence of superfecundation and of double paternity in the general eyes because of hypopigmentation and translucency of the iris. population. Acta Genet Med Gemellol 1993; 42: 257–262.

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3 Blickstein I. Superfecundation and superfetation: lessons from the past 7 Bothwell J. Pigmented lesions in tyrosinase-positive oculocutaneous albinos: a study in on early human development. J Matern Fetal Neonat Med 2003; 14(4): black South Africans. Int J. Dermatology 1997; 36: 831–836. 217–219. 8 Yakubu A, Mabogunje OA. Skin cancer in African albinos. Acta Oncol 1993; 32(6): 4 Girela E, Lorente JA, Alvarez JC, Rodrigo MD, Lorente M, Villanueva E. Indisputable 621–622. double paternity in dizygous twins. Fertil Steril 1997; 67: 1159–1161. 9 Lookingbill DP, Lookingbill GL, Leppard B. Actinic damage and skin cancer in albinos 5 Okulicz JF, Shah RS, Schwartz RA, Janniger CK. Oculocutaneous albinism. J Eur Acad in northern Tanzania: ﬁndings in 164 patients enrolled in an outreach skin care Dermatol Venereol 2003; 17(3): 251–256. program. J Am Acad Dermatol 1995; 32(4): 653–658. 6Grnskov K, Ek J, Brondum-Nielsen K. Oculocutaneous albinism. Orphanet J Rare Dis 10 Aquaron R. Oculocutaneous albinism in Cameroon. A 15-year follow-up study. 2007; 2: 43. Ophthalmic Paediatr Genet 1990; 11(4): 255–263.

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