Biomedical subjects
Publications and source records attributed to A E Fryer.
Two sibs with the branchio-oculo-facial syndrome are reported. They both have orbital haemangiomatous cysts, which is a previously unreported feature. Both parents are clinically normal and unrelated. This disorder has been reported showing autosomal dominant transmission so this family could represent either an autosomal recessive form or germline mosaicism for the dominant gene.
A child is reported with a scalp lipoma and underlying bony skull defect and porencephaly. The clinical picture is compatible with a diagnosis of encephalocraniocutaneous lipomatosis, although there is no alopecia overlying the lipoma and no scleral lesions. In addition, this child has unilateral ptosis and syndactyly. This report extends our appreciation of the phenotype of this neurocutaneous disorder.
The distinction between the cardio-facio-cutaneous syndrome (CFC) and the Noonan syndrome (NS) has been based on the presence of a characteristic facies, abnormal hair and skin, and sporadic occurrence. However, all reports of the CFC syndrome comment on the similarity between it and NS, and its sporadic nature is now debatable. This report demonstrates the evolution of the clinical phenotype in a patient with the CFC syndrome and prompts us to question the validity of separating CFC from NS.
OBJECTIVES: To establish the frequency of fits and mental retardation in an unbiased group of tuberous sclerosis patients. METHODS: Known tuberous sclerosis families with more than one affected person were ascertained for a genetic linkage study. A number of members were born after genetic counselling had been given after identification of the proband. These subjects were then carefully examined clinically and in many cases with cranial computerised tomography, renal ultrasound, and skeletal survey but not echocardiography. They provide an unbiased group of tuberous sclerosis patients and allow affected patients with normal intellect to be diagnosed. PATIENTS: Thirty-seven tuberous sclerosis families were ascertained and 26 patients born after the family proband were identified. RESULTS: Sixteen of these 26 patients suffered fits (62%) and 10 patients were mentally retarded (38%). CONCLUSIONS: A lower incidence of fits and mental retardation has been found in an unbiased sample of tuberous sclerosis patients. The lifetime risk for fits might be higher had we been able to follow the patients for longer. However, we believe these are more appropriate figures to use in genetic counselling for this disease.
A large family with Wagner's vitreoretinal degeneration but none of the non-ocular features of Stickler's syndrome has been studied with gene probes for type II collagen. Recombination has been observed, thus excluding type II collagen as the site of mutation in this family. This report supports other published evidence that the Wagner-Stickler syndrome is genetically heterogeneous.
Forty sets of parents and 24 sibs of patients with tuberous sclerosis were investigated by an extensive protocol, including clinical examination of skin, hair, and oral cavity, direct and indirect ophthalmoscopy, cranial CT scan, renal ultrasound, and a radiological skeletal survey. None of the clinical examinations provided evidence that any of the subjects was affected. Similarly, the cranial CT scan, renal ultrasound, and skeletal survey failed to identify any occult gene carriers. All of these investigations showed abnormalities in some parents but none was diagnostic. This study shows the difficulties in interpretation that these investigations may produce with consequent problems for genetic counselling. The study does not support the routine use of these tests. There are published reports where the diagnosis of tuberous sclerosis has been made in adults exclusively on a CT scan and an argument can be made for including this investigation. There is no indication for performing renal ultrasound nor skeletal x rays in parents who have normal clinical examinations.
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Linkage analysis was undertaken in nineteen families with tuberous sclerosis by use of 26 polymorphic markers. All affected members fulfilled strict diagnostic criteria and unaffected members were rigorously investigated to confirm their status. Maximum lod scores were 1.20 for adenylate kinase 1 (AK1) at zero recombination and 3.85 for the ABO blood group at zero recombination (confidence limits 0-0.10). These findings support the assignment of the gene for tuberous sclerosis to the distal long arm of chromosome 9.
Linkage analysis was undertaken in six families with tuberous sclerosis (TS) using a restriction fragment length polymorphism detected by v-abl. No recombinants were observed in 13 informative meioses (four phase known) giving a maximum lod score of 3.18 at zero recombination (confidence limits 0 to 0.15). This provides further evidence for the assignment of TS to 9q34 and should facilitate cloning of the structural gene, genetic counselling, and first trimester prenatal diagnosis.
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