Diagnostic and genetical aspects of tuberous sclerosis.

There have been many reviews of tuberous sclerosis (Critchley and Earl, 1932; Ross and Dickerson, 1943; Dawson, 1954; Reed, Nickel, and Campion, 1963; Paulson and Lyle, 1966; Lagos and Gomez, 1967). The classical features, epilepsy, mental retardation, and adenoma sebaceum, are found in most patients with tuberous sclerosis, while retinal tumours (phakomas), visceral tumours, skeletal lesions, and other cutaneous manifestations are noted less frequently. The complete syndrome is easily recognized in the older child and the adult, but in infancy and childhood the diagnosis may be difficult before the appearance of adenoma sebaceum. Convulsions, the most frequent presenting symptom, often begin in infancy and childhood, and may take the form of infantile spasms. Apart from adenoma sebaceum, a variety of skin manifestations occurs, shagreen plaques, subcutaneous fibromata, caf&-au-lait spots, periungual and subungual fibromata, cervical polypi or tags, and areas of depigmentation. Recently, Chao (1959) has called attention to depigmented areas of skin as the earliest skin lesion in tuberous sclerosis. In the course of treating 39 children with infantile spasms over a two-year period, Gold and Freeman (1965) found that of the children with areas of depigmented skin, 6 subsequently developed other manifestations of tuberous sclerosis. Crichton (1966) examined 174 children with infantile spasms, and of 11 with tuberous sclerosis, all had areas of depigmentation. Early diagnosis of tuberous sclerosis would enable the paediatrician to provide a more realistic prognosis for the patient and would also greatly assist genetic counselling. In the course of a survey of tuberous sclerosis in the area of the Oxford Regional Hospital Board, we were able to examine 18 patients with tuberous sclerosis. This paper describes the clinical features and genetic data ofthese patients, with particular emphasis on the diagnostic criteria in infancy. A further 14 patients who were reported at necropsy to have died from tuberous sclerosis of the brain are also included in the study.