Congenital hypopigmented macules on a healthy child


You are asked to evaluate an African American boy aged 4 years with a birthmark on his back and right arm. He is healthy with normal growth and development. What's the diagnosis?

You are asked to evaluate an African American boy aged 4 years with a birthmark on his back and right arm. He is healthy with normal growth and development.

Blaschkoid Hypopigmentation

Lines of Blaschko are thought to represent pathways of epidermal migration and proliferation during fetal development.11 They differ from dermatomes that represent areas of skin innervated by a single nerve. Lines of Blaschko are usually invisible unless genetic mutations result in mosaicism that alters the pigmentation, proliferation, and/or differentiation of epidermal cells.11 The lines are visible and present in S-shaped, V-shaped, or even U-shaped patterns.2 They are usually seen on either the scalp, face, trunk, and/or limbs.2

Genetic mosaicism can occur due to chromosomal abnormalities such as a nondisjunction event that takes place before zygote formation (meiosis) or after a postzygotic event (mitosis). In both cases, cells will have three copies of a chromosome, leading to trisomy. To create a diploid zygote, the embryo undergoes trisomic rescue where one of the chromosomes in the trisomy is lost to form a diploid cell. However, not all the cells will have one chromosome from each parent after trisomic rescue. Instead, some cells will be heterodisomic or isodisomic. The result is at least 2 different cell lines present in an individual derived from 1 zygote. In our patient’s case, these 2 cell lines may have differing amounts of melanocytes present which can give rise to different skin lesion phenotypes such as hyperpigmentation or hypopigmentation.3 The resulting phenotype is known as Blaschko lines. In addition to hyperpigmentation and hypopigmentation, Blaschko lines can sometimes be seen as warty or inflamed before becoming hyperpigmented.2

Another type of mosaicism that can cause Blaschko lines is through epigenetics and termed as lyonization.8 This occurs in females where one X-chromosome in somatic cells is inactivated. In some cases, lyonization could lead to a manifesting heterozygote in the form of Blaschko lines.4

Differential of hypopigmentation

Ash leaf macules of tuberous sclerosis

Waardenburg syndrome


Nevus depigmentosus

Ash leaf macules of tuberous sclerosis: When looking at the patient’s findings, he presents with hypopigmented macules since birth. A diagnosis that can be associated with this symptom is tuberous sclerosis. However, tuberous sclerosis presents with characteristic ash-leaf spots that differ from the swirls and delineation nature of Blaschko lines.6 Other cutaneous findings in tuberous sclerosis include facial angiofibromas, periungual fibromas, hypomelanotic macules, and connective tissue nevi. Compared to Blaschko lines forming through errors of cell migration in embryogenesis, tuberous sclerosis is caused by mutations in tuberous sclerosis complex (TSC).13 This mutation leads to activation of the mTOR signaling pathway that decreases melanocyte production leading to the hypopigmented macules seen in patients with tuberous sclerosis.13

Waardenburg syndrome: Waardenburg syndrome is a genetic condition that affects the skin through genetic mutations in the MITF gene. When MITF is genetically altered, it has been shown to affect melanocytes, leading to hypopigmentation of the skin.12 A key difference between Waardenburg syndrome and Blaschko lines is that Waardenburg syndrome not only affects the skin, but also affects ears, eyes, and hair through genetic mutations in SOX 10, EDN3, EDNRB, and PAX312. Patients can have congenital hearing loss, different colored irises, and a patch of white hair above their forehead known as “white forelock."12 Depending on what genes are affected, Waardenburg Syndrome can be further differentiated into Types I-Types IV. Types I and II have an autosomal dominant inheritance while Types III and IV have an autosomal recessive inheritance.12

Piebaldism: Another diagnosis that can lead to hypopigmented macules as a cutaneous finding includes Piebaldism, an autosomal dominant inherited condition. Piebaldism results when genes, KIT and SNIA2, are mutated.10 KIT2 is an important signaling protein of melanocytes during embryogenesis. It activates the Ras/MARK pathway which contributes to production of melanin.9 SIAD2 is crucial to neural crest cell production which helps produce melanocytes.10 When either of these proteins are mutated, melanocyte production is decreased and hypopigmented macules can be seen on exam. In contrast to Blaschko lines, the hypopigmented areas are symmetrical on each side of the body.10 In addition to hypopigmentation, Piebaldism shares the “white forelock” characteristic seen in Waardenburg syndrome.

Nevus depigmentosus: Nevus depigmentosus, or achromic nevus, is a congenital skin condition seen at birth or during changes in development. Patients present with a serrated, unilateral, pale patch of skin that remains stable over time and does not cross the midline.5 Genetic mosaicism can lead to nevus and thereby cause a decreased production of melanocytes or even decreased production in melanin.7 There are 3 variants of Nevus depigmentosus: Isolated (solitary patch), Segmental (patch following Blaschko lines), and Systematized (swirled areas of skin).7 In 50% of patients diagnosed with Nevus depigmentosus, the discolored patch of skin is isolated.7 This single, isolated patch distinguishes nevus depigmentosus from the many lines of Blaschko all over our bodies.


Genetic mosaicism can be tested prenatally through amniocentesis from the uterus or chorionic villus sampling from the placenta. Furthermore, a karyotype can be done after birth to detect any chromosomal abnormalities if present. When a child presents with cutaneous lesions at birth, he or she can be evaluated based on history, presentation, and initial differential diagnoses listed above. Our patient was diagnosed with hypopigmented Blaschko lines by looking at the delinear presentation of the lines, characteristics of pigmentation, and their location.1


Although not required, for patients that wish to treat hyperpigmented Blaschko lines, they have the option to be treated with laser or topical hydroquinone and sunscreen. The treatment for patients with hypopigmented Blaschko lines is the option to use cosmetic cover up, pigmentary tattoos, dermabrasion, and phototherapy.

Our Patient

Our patient’s mother was worried about the lesions on her son’s back which were present since birth so she brought the patient in to be evaluated. The patient was noted to have hypopigmented Blaschko macules on the midline of his back and extensor surface of his right arm. Furthermore, the patient had an MRI brain/spine done with no abnormal findings. In light of his normal growth and development and MRI findings, we were able to reassure his mother that he would continue to grow and develop normally.

When caring for patients with lesions similar to our patient, it is important to thoroughly educate these patients on the causes behind Blaschko lines. We must also be mindful to understand the role that these lesions may play on the emotional and mental health of our patient.


  1. Alkhowailed, Mohammad S et al. “Clinical Approach to Linear Hyperpigmentation: A Review Article.” Clinical, cosmetic and investigational dermatology vol. 14 23-35. 8 Jan. 2021, doi:10.2147/CCID.S280819
  2. Cunliffe, Tim. “Blaschko's Lines.” Primary Care Dermatology Society, 26 Aug. 2021,
  3. Di Lernia, Vito. “Linear and whorled hypermelanosis.” Pediatric dermatology vol. 24,3 (2007): 205-10. doi:10.1111/j.1525-1470.2007.00387.x
  4. Happle, R. “Lyonization and the lines of Blaschko.” Human genetics vol. 70,3 (1985): 200-6. doi:10.1007/BF00273442
  5. Hewedy, E. , Hassan, A. , Salah, E. , Sallam, F. , Dawood, N. , Al-Bakary, R. , & Al-Sharnoby, H. (2013). Clinical and ultrastructural study of nevus depigmentosus. Journal of Microscopy and Ultrastructure, 1 (1). doi: 10.1016/j.jmau.2013.06.006
  6. Jindal, Rashmi et al. “Ash-leaf spots or naevus depigmentosus: a diagnostic challenge.” BMJ case reports vol. 2013 bcr2012007008. 10 Jun. 2013, doi:10.1136/bcr-2012-007008
  7. Jun Yi Wong, Daniel. “Achromic Naevus.” Achromic Naevus | DermNet NZ, 2013,
  8. Kouzak, Samara Silva et al. “Cutaneous mosaicisms: concepts, patterns and classifications.” Anais brasileiros de dermatologia vol. 88,4 (2013): 507-17. doi:10.1590/abd1806-4841.20132015
  9. Oiso, Naoki, et al. “Piebaldism.” The Journal of Dermatology, vol. 40, no. 5, 2012, pp. 330–335.,
  10. “Piebaldism: Medlineplus Genetics.” MedlinePlus, U.S. National Library of Medicine, 18 Aug. 2020,
  11. Senner, Sonja, et al. “Linear Patterns of the Skin and Their Dermatoses.” JDDG: Journal Der Deutschen Dermatologischen Gesellschaft, vol. 18, no. 4, ser. 2020, 15 Apr. 2020, pp. 341–364. 2020,
  12. “Waardenburg Syndrome.” NORD (National Organization for Rare Disorders), 22 June 2015,
  13. Yang, Fei et al. “Dysregulation of autophagy in melanocytes contributes to hypopigmented macules in tuberous sclerosis complex.” Journal of dermatological science vol. 89,2 (2018): 155-164. doi:10.1016/j.jdermsci.2017.11.002
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