A number of observations have repudiated the former belief that the human embryo is naturally shielded against exogenous causes of maldevelopment. Irradiation during the first trimester, rubella and CMV infections, severe hypothyroidism of the mother during this same period, and the action of alcohol, vitamin A, and thalidomide have all been observed, among a multitude of other agents, to give rise to serious disorders of development. Quite relevant to the neurologist, the offspring of mothers receiving anticonvulsant drugs during the early months of pregnancy have a slightly increased risk of developing birth defects (approximately 5 percent, compared to 3 percent for the general population—see “Teratogenic Effects of Antiepileptic Medications” in Chap. 15). Cleft lip and palate are the most common anomalies attributable to anticonvulsant drugs; other craniofacial defects, spina bifida, minor cardiac defects, and dysraphisms have also been reported at a slightly increased rate. Claims and counterclaims have been made concerning the pathogenicity of numerous other substances. Mainly, the data are from animals given amounts far in excess of any possible therapeutic doses in humans. The data from humans are so meager from a multitude of such substances that they are not discussed here. The reader may refer to the article by Kalter and Warkany for further information.
As stated earlier, there are two broad categories of neurocutaneous diseases. In one, the infant is born with a special type of skin disease or develops it in the first weeks of life; in the other forms, the cutaneous abnormality, although often present in minor degree at birth, later evolves as quasineoplastic disorders. The quasineoplastic disorders to which van der Hoeve in 1920 applied the term phakomatoses (from the Greek phakos, meaning “mother spot,” “mole,” or “freckle”) are tuberous sclerosis, neurofibromatosis, and cutaneous angiomatosis with central nervous system (CNS) abnormalities, which have many features in common: hereditary transmission, involvement of organs of ectodermal origin (nervous system, eyeball, retina, and skin), slow evolution of lesions in childhood and adolescence, a tendency to form hamartomas (benign tumor-like formations because of maldevelopment), and a disposition to fatal malignant transformation. These disorders are discussed below and listed in Table 37-4.
Tuberous sclerosis is a congenital disease of hereditary type in which a variety of lesions, because of a limited hyperplasia of ectodermal and mesodermal cells, appear in the skin, nervous system, heart, kidney, and other organs. It is characterized by the triad of adenoma sebaceum, epilepsy, and developmental delay. Hypomelanotic skin macules (“ash-leaf” lesions) and the subepidermal fibrotic “shagreen patch” are diagnostic features.
It is stated that Virchow recognized scleromas of the cerebrum in the 1860s and that von Recklinghausen reported a similar lesion combined with multiple myomata of the heart in 1862, but Bourneville’s articles, appearing between 1880 and 1900, presented the first systematic accounts of the disease and it was he who related the cerebral lesions to those of the skin of the face. Vogt in 1890 fully appreciated the significance of the neurocutaneous relationship and formally delineated the triad of facial adenoma sebaceum, epilepsy, and developmental delay. “Epiloia,” a term for the disease introduced by Sherlock in 1911, never gained general acceptance. These and other historical aspects are reviewed in Gomez’s monograph.