A 5 -month old boy was evaluated for white spots on his skin that were first noticed at age 1 week. New lesions had continued to appear, and the older lesions were increasing in size. There was no history of a previous eruption or redness in the affected areas. Birth, medical, and developmental history all were negative for abnormalities. Family history was negative for skin disease or similar lesions.
Physical examination revealed a 5-cm hypopigmented oval patch on the right buttock (Figure), an 8-mm hypopigmented oval patch on the right testicle, and multiple 3-mm to 7-mm hypopigmented oval macules scattered over the trunk. The remainder of the physical examination, including a neurological examination, was normal.
Because of the suspicion of tuberous sclerosis in the setting of a young infant with multiple hypomelanotic macules, the patient was sent for appropriate diagnostic evaluation. Renal ultrasound and ophthalmologic examination were normal. Computed tomography of the head revealed a calcified subependymal nodule in the left lateral ventricle and a cortical tuber in the right superior frontal and precentrai gyri. The patient subsequently developed seizures clinically consistent with infantile spasms and confirmed by electroencephalogram.
Figure. Photograph of infant's buttock with hypopigmented macules.
Hypomelanotic macules and tuberous sclerosis complex
Tuberous sclerosis is a complex genetic disorder characterized by cutaneous and neurologic abnormalities and visceral tumors of the heart and kidney. It was first reported by Von Recklinghausen1 in 1862 but was named tuberous sclerosis by Bourneville2 in 1880. Inheritance is autosomal dominant, with nearly 100% penetrance. Mutations in the TSCl or TSC2 gene have been documented, and nearly two-thirds of those affected have tuberous sclerosis as the result of a new genetic mutation.3
The diagnosis of tuberous sclerosis is based on clinical findings that are divided into major and minor diagnostic features (Sidebar). Either two major features or one major feature plus two minor features are required for a definite diagnosis.3 This patient presented with three major features (more than three hypomelanotic macules, cortical tuber, and subependymal nodule), consistent with a definite diagnosis of tuberous sclerosis.
The most common and earliest cutaneous finding in children is hypomelanotic macules. These lesions are present at birth or most often appear in the first few years of life. Once present, they tend to remain stable in shape and size. Lesions are commonly on the trunk and can be round ("thumbprint"), confetti-like, oval, linear, or the classic ash-leaf (lance-ovate) shape. They range in size from 1 millimeter to several centimeters, and the number of lesions may range from a few to more than 75.4 If they are difficult to visualize, Wood's lamp examination accentuates the macules in fairskinned children.
Hyopigmented lesions are a common presentation in the primary care setting. It often is difficult to know which lesions require no further evaluation and which lesions may represent skin manifestations of a more complex problem. The differential diagnosis of hypopigmented or depigmented lesions in children includes post-inflammatory hypopigmentation, pityriasis alba, tinea versicolor, vitiligo, nevus depigmentosus, nevus anemicus, pigmentary mosaicism, albinism, and piebaldism. These disorders most often are distinguished from the white spots of tuberous sclerosis by history and physical exam.
A history of previous localized inflammation points toward a diagnosis of post-inflammatory hypopigmentation. The lesions of pityriasis alba and tinea versicolor may have associated scale and are distributed on the face, neck, and trunk. A KOH preparation will be positive with the latter. Vitiligo is depigmented as opposed to hypopigmented with a characteristic complete loss of pigment and sharply demarcated borders. A nevus depigmentosus is often congenital and usually solitary. Nevus anemicus is a pale or mottled macular area secondary to increased vascular tone and not a pigment abnormality. The borders of a nevus anemicus lesion will disappear when the lesion is pressed with a glass slide as the surrounding normal skin is blanched (diascopy).5 Albinism and piebaldism can be distinguished from tuberous sclerosis by their associated clinical features.
Given that the clinical spectrum of tuberous sclerosis can range from a single cutaneous hamartoma to involvement of multiple organ systems, an evaluation and management plan was developed by the Clinical Issues Panel at the Tuberous Sclerosis Consensus Conference3 (revised January 19996). Evaluation of newly diagnosed patients should include medical and family history (for features of tuberous sclerosis), physical exam with special attention to dermatologie findings, cranial CT/MRI, renal ultrasound, ophthalmologic exam, neurodevelopmental and behavioral evaluation, electrocardiogram, echocardiogram if cardiac symptoms are present, and electroencephalogram if seizures are present.6
The prognosis of tuberous sclerosis depends on the severity of the disorder and the presence of neurologic involvement.7 Treatment may include anticonvulsant therapy for seizures, surgical intervention for visceral tumors of the heart and kidney, laser therapy for facial angiofibromas,8 and supportive care for associated medical conditions, including developmental delay.
1. Von Recklinghausen F. Ein Herz von einem Neugeborenen welches mehrere theils nach ausssen, thelis nach den Hohlen prominierende Tumoren (Myomen) hug. Verhandl Gesellsch Geburtsh. 1863;15:73-75.
2. Bourneville DM. Contribution a Petude de Pidiote: sclerose tuberose des circonvolutions cerebrale: Idiote et epilepsic hémiplegique. Arch Neurol. 1 880; 1 : 8 1 -9 1 .
3. Roach ES, Gomez MR, Northrup H. Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria. JChildNeuml. 1998;13(12):624-628.
4. Palier AS, Mancini AJ. Hurwitz Clinical Pediatric Dermatology: A Textbook of Skin Disorders of Childhood And Adolescence. 3rd ed. Philadelphia, PA: WB Saunders; 2006:266-279.
5. Vanderhooft SL, Francis JS, Pagon RA, Smith LT, Sybert VP. Prevalence of hypopigmented macules in a healthy population. J Pediatr. 1996;129(3):355-361.
6. Roach ES, DiMario FJ, Kandt RS, Northrup H. Tuberous Sclerosis Consensus Conference: recommendations for diagnostic evaluation. National Tuberous Sclerosis Association. J Child Neurol. 1999;14(6):401-407.
7. Webb DW, Fryer AE, Osborne JP. Morbidity associated with tuberous sclerosis: a population study. Dev Med Child Neurol. 1996;38(2): 146-155.
8. Sweeney SM. Pediatric dermatologie surgery: a surgical approach to the cutaneous features of tuberous sclerosis complex. Adv Dermatol. 2004;20: 1 17-135.