Page 253 - The Netter Collection of Medical Illustrations - Integumentary System_ Volume 4 ( PDFDrive )

Plate 9-12 Genodermatoses and Syndromes

TUBEROUS SCLEROSIS

Tuberous sclerosis (Bourneville’s syndrome) is a multi-
system disease that often manifests with cutaneous find-
ings. It is inherited in an autosomal dominant manner
and is directly caused by a defect in one of two genes,
TSC1 or TSC2, usually due to a spontaneous mutation.
TSC1 has been shown to encode the hamartin protein,
whereas TSC2 gene encodes the tuberin protein. The
skin, central nervous system (CNS), cardiovascular,
respiratory, visual, and musculoskeletal systems are
affected. This genodermatosis has an extremely variable
phenotype. At one extreme is the severely disabled and
mentally delayed individual with severe seizure disor- Tuber of cerebral cortex. Consisting of many astrocytes,
ders; at the other end of the spectrum is the individual scanty nerve cells, some abnormal sites Multiple small tumors. Caudate nucleus
with mild skin disease and unappreciable CNS disease. and thalamus projecting into ventricles
Clinical Findings: The incidence of tuberous sclero-
sis is approximately 1 in 15,000, and the disease affects
all races and genders equally. Infants and young chil-
dren may present with primary CNS disease with the
onset of seizures. All children with new-onset seizures
should be evaluated for the cutaneous findings of tuber-
ous sclerosis; if these are located, the child should be
further evaluated for the possibility of this diagnosis.
Mental delay may be noticeable, because the child may
not meet normal developmental milestones. Other
brain anomalies have been reported to occur in tuber-
ous sclerosis, including astrocytomas, hydrocephalus,
cortical tubers, and subependymal tumors. Cardiac
rhabdomyomas may manifest with a murmur and are
best evaluated with the use of an echocardiogram. The
lungs are rarely involved with lymphangiomyomatosis.
Cutaneous findings are often the earliest findings
of the disease, even before the onset of CNS disease.
The “ash leaf” macule is the first cutaneous find- CT scan. Showing one of many
ing; it is represented by a hypopigmented to depig- Adenoma sebaceum. Over both cheeks and bridge of nose calcified lesions in periventricular area
mented macule in the shape of an ash leaf. Other
hypopigmented macules are prominent components
of tuberous sclerosis and include “confetti” macules
and polygonal hypopigmented macules. The isolated Multiple small
finding of a hypopigmented macule in infants should tumors in kidney
make one consider and evaluate for the diagnosis of
tuberous sclerosis. Approximately 0.25% of normal
newborns have a hypopigmented macule with no other
evidence of tuberous sclerosis.
Connective tissue nevi are frequently seen in this
disease and can manifest as small plaques or dermal
nodules. These nevi have been termed “shagreen
patches.” Skin biopsies are required to diagnose a con-
nective tissue nevus. Koenen tumors, a type of periun-
gual fibroma, are a feature of the disease and can be Tuber of ocular fundus
seen on a solitary digit or on multiple digits of the hands
and feet. Café-au-lait macules are occasionally seen. At
puberty or slightly before, the presence of facial angio-
fibromas may become noticeable. These facial tumors
tend to increase in size and number over time. They
cause significant morbidity and psychological harm to Rhabdomyomas
the affected individual. These angiofibromas have been of heart muscle Depigmented skin area
given the name adenoma sebaceum, and in some cases
they are the initial sign of the disease. They are fre-
quently misdiagnosed as early acne, and only after lack signaling pathway. When these proteins are mutated, to evaluate for the possibility of retinal astrocytic
of response to therapy or referral to a dermatologist are the inhibition is removed, and the mTOR pathway is hamartomas (phakomas). Facial angiofibromas can
they accurately identified. These facial growths cause allowed to signal uncontrolled. This leads to unregu- be surgically removed by many means. Laser vaporiza-
significant disfigurement, and many individuals seek lated cell division and the production of various tumors. tion and more traditional surgical methods have been
therapy to lessen the appearance of these tumors. Treatment: Therapy needs to be individualized for used to remove or lessen the appearance of these
Pathogenesis: When defective, hamartin and tuberin each patient. Those with seizure disorders and CNS tumors. No therapy is required for the hypopigmented
have been shown to cause tuberous sclerosis. They tumors require the expertise of a neurologist or macules or the connective tissue nevi. All patients
are both tumor suppressor proteins that function by neurosurgeon or both. Antiseizure medications are fre- should be monitored routinely by their pediatrician for
interacting with a G protein. This interaction inhibits quently required for prolonged periods. Routine oph- evaluation of developmental milestones and physical
the so-called mammalian target of rapamycin (mTOR) thalmological examinations should be recommended examinations.

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 239