Extracutaneous findings may be evident, but the majority of children (especially if small, localized areas of hypopigmentation) have no systemic involvement. Skin Other possible associated findings Parents will often express concerns based on outdated limited studies that focus on children with extracutaneous findings. As the majority of children will have no significant systemic findings, most parents can be reassured after collaborative evaluation with the primary care clinician and perhaps pediatric dermatology. Unlike the name implies, lesions are not devoid of pigment entirely as in vitiligo. Skin Well-defined nonprogressive hypopigmented patch, usually solitary, most often seen on the trunk but can be present anywhere; rare associated systemic findings (neurologic, ocular, and/or musculoskeletal); risk is greater in patients with extensive lesions involving large areas. Age at diagnosis is earlier in black children owing to a contrast of lesion compared with adjacent normal skin and later in lighter skin children for the same reason. Clinical variants Coupe clinical criteria Treatment is cosmetic. Various procedures are reported with variable success rates. Cosmetic camouflage makeup is often easy and very effective. With subtle lesions keeping the surrounding skin covered with sunscreen and allowing a little tanning of the hypopigmented nevus can provide camouflage. Other options Parents are often worried first about a fungal infection and then if the lesions will ever resolve. Treatment results are varied and often incomplete. However, one can reassure parents that the lesions will not progress. 4.1. Nevus depigmentosus. Types Four main types. Proposed diagnostic criteria for WS1 Two major or 1 major plus 2 minor Early evaluation for hearing and eye defects, rare association with musculoskeletal abnormalities of the arms and chest, and protection and camouflage of pigmentary anomalies should be a high priority. A good family history may uncover other affected family members in up to 50% of cases. Is this vitiligo? No, this can be easily differentiated from vitiligo, as piebaldism is a congenital and familial disorder. Will this ever go away? This is a lifelong condition. However, areas of involvement may enlarge or improve. There are also rare associations with neurofibromatosis, Hirschsprung disease, and other medical conditions; therefore, regular follow-up with their primary care provider and dermatologist is important. Can I pass this on to my children? Yes, this is an autosomal dominant disorder. 4.3. Symmetric stable hypopigmented/depigmented macules in piebaldism. In many cultures, albinism carries significant stigma with it. This must be discussed with the parents. Some types of OCA can improve over time. A careful exam of the newborn revealing even subtle pigmentation of hair, eyes, and nevi should predict a milder course with some progressive pigmentation and improvement in visual function. 4.4. Partial albinism. Skin Neurologic Infancy to early childhood, brain tumors including cortical tubers, subependymal nodules and giant cell astrocytomas leading to intractable seizures. Cardiac Infancy to early childhood, congenital cardiac rhabdomyomas. Pulmonary Adulthood, pulmonary lymphangiomyomatosis in women between the third and fifth decades. Renal Late childhood, renal hamartomas. Ophthalmologic Adulthood, retinal hamartomas, increased incidence with age. Dental Late childhood, dental pits. Multidisciplinary approach; MRI or CT of brain to identify subependymal giant-cell tumors; ultrasound, CT, or MRI of the kidneys to identify angiomyolipomas; in women with TSC, pulmonary function testing, and CT of the lungs to identify subclinical lymphangiomyomatosis. The Tuberous Sclerosis Alliance suggests the following surveillance: Will these skin findings get worse with time? Facial angiofibromas can become more numerous with age, but there are treatments available for this. Will my child have trouble in school? Some children may require extra support in school. Your pediatrician will help monitor your child’s development and provide referrals if necessary. Will this affect my child’s life expectancy? Certain tumors that can be associated with TSC can be life-threatening which is why routine monitoring and surveillance are so important, even if your child is not having specific symptoms. Will my child pass this off to his or her children? An adult with TSC has a 75% chance of passing this condition along to his/her child so it is important to meet with a genetic counsellor prior to becoming pregnant.
CHAPTER
4
WHITE LESIONS (MACULES, PATCHES, AND PAPULES)
Nevoid Hypopigmentation
Synonym
Congenital mosaic hypopigmentation, Blaschkoid dyspigmentation, incontinentia pigmenti achromians, hypomelanosis of Ito, nevus depigmentosus.
Inheritance
Rarely when there is gonadal involvement.
Prenatal Diagnosis
n/a
Incidence
1:8,000-10,000 persons in general population (but may be up to 0.5% of newborns), with small, localized variants (nevus depigmentosus).
Age at Presentation
Present at birth in most; ~75% present for evaluation by age 2 years; in light-skin babies may not be evident until some darkening of the uninvolved skin shows contrast with the involved skin.
Pathogenesis
Genetic mosaicism; multiple sporadic mutations in various genes have been identified.
Key Features
Differential Diagnosis
Incontinentia pigmenti, vitiligo, postinflammatory hypopigmentation, nevus anemicus.
Laboratory Data
Genetic mutations may be identified in the affected skin and rarely in peripheral blood, especially when the skin lesions are widespread.
Management
The pigmentary abnormality is asymptomatic. Cover-up and makeup can alleviate cosmetic concerns. Careful physical examination, review of systems, and developmental examination in conjunction with the primary care provider. When there is concern for systemic findings, genetics counseling will help to determine if a true genodermatosis is present and to assist in future pregnancy planning. Neurology, ophthalmology, and other referrals as necessary are based on clinical findings.
Prognosis
Is based on the associated systemic findings. Prognosis of pigmentation abnormalities is excellent.
PEARL/WHAT PARENTS ASK
Skin
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Associated Findings 
Nevus Depigmentosus
Synonym
Achromic nevus, hypopigmented mosaicism.
Inheritance
n/a
Prenatal Diagnosis
Usually sporadic but occasionally autosomal dominant or recessive.
Incidence
Common, 0.4% to 0.7% of the population.
Age at Presentation
Birth or early neonatal period; often goes undiagnosed for months to years because most lesions are small and may not be easily visible until the contrast between normal and involved skin is enhanced by sun exposure.
Pathogenesis
Presumed to be a developmental defect resulting in altered synthesis and transfer of normal melanosomes to adjacent keratinocytes; marker of genetic mosaicism with various somatic genetic markers.
Key Features
Differential Diagnosis
Vitiligo, ash leaf macules of tuberous sclerosis, nevus anemicus.
Laboratory Data
Some reports of specific genetic markers though none have been developed yet for routine clinical use.
Management
Prognosis
As the majority of these lesions are single and not associated with any systemic abnormalities, overall prognosis is excellent. The actual lesions tend not to spontaneously repigment.
PEARL/WHAT PARENTS ASK
Skin
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Associated Findings 
Waardenburg Syndrome
Synonym
n/a
Inheritance
Prenatal Diagnosis
PAX3 prenatal testing is available, though it cannot predict the severity of the condition in a fetus.
Incidence
1:42,000-50,000 people.
Age at Presentation
At birth.
Pathogenesis
Various gene defects. The predominant clinical findings (depigmentation of hair and skin) are caused by abnormal melanocyte distribution from embryogenesis. These findings as well as noncutaneous findings are triggered by PAX3 and other genetic mutations that control neural crest differentiation.
Key Features
Differential Diagnosis
Piebaldism, vitiligo, albinism.
Laboratory Data
Molecular genetic testing can identify affected genes.
Management
Women at risk for having a child with WS1 should have genetic testing and receive folic acid supplementation to reduce the incidence of possible neural tube defects.
Prognosis
Based on the specific abnormalities by type. Most patients live a normal life unless there are complications associated with type-specific clinical findings (ie, Hirschsprung disease). Referrals to ENT and gastroenterology may be necessary by type. Hearing aids and/or cochlear implants depending on the presence of unilateral or bilateral deafness. Phototherapy and skin and hair camouflage may help with pigmentary abnormalities.
PEARL/WHAT PARENTS ASK
Skin
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Associated Findings 
Piebaldism
Synonym
White forelock, poliosis circumscripta.
Inheritance
Autosomal dominant.
Prenatal Diagnosis
n/a
Incidence
Not clearly known, but some sources cite 1 in 20,000 children.
Pathogenesis
c-Kit proto-oncogene mutation in affected skin and hair follicles; is involved in normal melanocyte development and function; clinical manifestations are determined by the site of the mutation; mutation in the Slug (SNAI2) gene has also been identified as a cause for this condition.
Age at Presentation
At birth.
Key Features
Patients present at birth often with a white forelock of hair (80%–90% of patients) along the frontal scalp; depigmented patches of skin at midline, often on forehead in a triangular configuration; may extend to the nose and may depigment eyelashes or eyebrows; unlike vitiligo, lesions are often located on ventral surfaces rather than extensor surfaces; other locations include the trunk and extremities; normal-to-hyperpigmented macules may be found within the confines of these depigmented patches; depigmentation of the skin and hair may progress or regress.
Differential Diagnoses
Vitiligo, Waardenburg syndrome, TSC, Vogt-Koyanagi-Harada syndrome, alopecia areata, Alezzandrini syndrome, underlying halo nevus.
Laboratory Data
No specific labs; biopsy reveals a complete absence of melanocytes in the involved skin. Melanocytes, however, may be noted in the normal to hyperpigmented regions.
Management
Very difficult to treat; cosmetic products (eg, Dermablend) can mask the dyspigmentation; regular sunscreen use to prevent sunburn (SPF-30 broad-spectrum); surgical therapies include autologous melanocyte grafting and micro-punch transplantation from unaffected epidermal sites have proven effective.
Prognosis
This is a lifelong disease process; normal lifespan.
PEARL/WHAT PARENTS ASK
Skin
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Associated Findings 
Albinism
Synonym
Oculocutaneous albinism (OCA).
Inheritance
Autosomal recessive.
Prenatal Diagnosis
n/a
Incidence
Overall worldwide 1:20,000 persons, though depends on the specific OCA type.
Age at Presentation
At birth.
Pathogenesis
Mutations in enzymes or other proteins involved in melanin synthesis lead to the clinical findings of each type of OCA.
Key Features
Differential Diagnosis
Hermansky-Pudlak syndrome, albinoidism, Chediak-Higashi syndrome, Griscelli syndrome, Elejalde syndrome, ocular albinism.
Laboratory Data
n/a
Management
Ophthalmology referral, lifelong sun protection.
Prognosis
No cure currently exists; supportive care; strict photo-protection to reduce the risk of skin cancer.
PEARL/WHAT PARENTS ASK
Skin
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Associated Findings 
Tuberous Sclerosis
Synonyms
Tuberous sclerosis complex (TSC), Bourneville’s disease, Bourneville-Pringle disease, epiloia (epilepsy, low intelligence, adenoma sebaceum).
Inheritance
Autosomal dominant; two-thirds are caused by sporadic mutations.
Prenatal Diagnosis
Diagnosis is based on clinical findings; prenatal diagnosis has been reported in the literature but is not standard.
Incidence
~1 in 6,000 births but ~1 case per 10,000 in the population because of mildly affected or asymptomatic patients; M = F, no racial predilection.
Age at Presentation
Can present at any age; in infants and children is often diagnosed/suspected during the evaluation of epilepsy, autism, or cardiac failure.
Pathogenesis
Mutations in TSC1 and TSC2, encoding for hamartin and tuberin respectively; both are tumor suppressor genes; these protein products form a complex and inhibit cell growth and proliferation; loss of function of either gene leads to unchecked proliferation.
Key Features
Differential Diagnosis
Multiple endocrine neoplasia syndrome type 1, Birt-Hogg-Dubé, Buschke-Ollendorff syndrome, polycystic kidney disease, vitiligo, piebaldism, nevus anemicus, nevus depigmentosus.
Laboratory Data
There are no specific laboratory tests to monitor. The diagnosis is based on clinical signs and radiographic features. Testing for TSC1 or TSC2 mutations can be done via polymerase chain reaction (PCR) amplification and DNA sequencing from a patient’s blood; can isolate causative gene mutation in 75% to 80% of cases.
Management
Prognosis
Variable depending on which signs and symptoms may be present. Those with mild symptoms can live a normal life. Those with severe disease may suffer from epilepsy, which is challenging to control, and developmental delay. All those affected with TSC are at risk for life-threatening brain tumors, kidney lesions, and lung tumors.
PEARL/WHAT PARENTS ASK
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