Phenotypic expression of a family with multiple endocrine neoplasia type 2A due to a RET mutation at codon 618.

BACKGROUND: Multiple endocrine neoplasia type 2A (MEN2A) is caused by missense mutations in the RET proto-oncogene on chromosome 10. This paper reports the phenotypic expression of a family with MEN2A, in which serine substitutes for cysteine at codon 618 in exon 10 of the RET gene. It was first claimed that medullary thyroid cancer (MTC) with this rare mutation led to mild disease; this has recently been updated to intermediate-high risk, based on stratified genetic information. METHODS: The family was mapped over six generations. In 1971 family members were invited to join a screening programme. Genetic testing was started in 1994. RESULTS: Twenty-two individuals with MTC were identified, 16 by the screening programme. One screened patient had a phaeochromocytoma and four had hyperparathyroidism. At surgery for MTC 12 patients had local tumour metastases and two young patients also had liver metastases. No screened patient died from MTC during a mean observation time of 19 years. Six other family members were diagnosed with MTC by signs and symptoms, five of whom died from MTC. CONCLUSION: Because of the great interindividual differences in tumour aggressiveness within the family it is impossible to predict whether an individual gene carrier will have an aggressive MTC or not. This unpredictability is an additional argument, besides those obtained in stratified genetic studies, for operating on gene carriers at young age.

[Phenotypic expression of a mutation in MEN 2A documented in a family in the western part of Sweden]. / Fenotypiskt uttryck av mutation vid MEN 2A kartlagd i västsvensk familj.

A missense mutation at codon 618 of the RET proto-oncogene is a rather unusual cause of multiple endocrine neoplasia 2A. We report the phenotypic expression of this specific RET mutation in a large Swedish family. The family was mapped back to the 18th century. Since 1971 the family has been included in a biochemical screening program, and since 1994 has undergone genetic screening. Twenty-seven individuals were found to have medullary thyroid carcinoma (MTC). Eighteen were detected by screening. The incidence of pheochromocytoma (4%) and hyperparathyroidism (7%) was low. Five individuals died of MTC, but of these none had been included in the screening program. One patient underwent prophylactic thyroidectomy after positive genetic screening. MTC tumor aggressivity differed markedly between gene carriers. The screening program shows that the clinical aggressivity of MTC can be mitigated by early and adequate surgical intervention.

Rearward-facing child seats--the safest car restraint for children?

During recent years the use of child restraints in cars in Sweden has rapidly increased. The fact that the different restraint systems prevent injuries has been substantiated, as is shown in this paper. The major emphasis is put on the benefits of using rearward-facing child seats for children 0 to 4 years of age. Attitudes concerning child safety in cars and the misuse problem are also discussed. Based on Volvo's accident material it is shown that the injury-reducing effect of the rearward-facing child seat is superior to all present types of child restraints in cars. This paper is mainly based upon Volvo's own traffic accident material. This paper is based upon accidents that occurred between the years 1976 and 1988 and comprises some 13,000 accidents involving approximately 22,000 people. In 1,500 of these accidents at least one child (0 to 14 years) was present in the vehicle. In addition to the collection of accident data, separate attitude studies have been carried out, concerning child safety in cars.