Clinical variability and molecular diagnosis in a four-generation family with X-linked Emery-Dreifuss muscular dystrophy.

AIM: To describe the clinical variability of X-linked Emery-Dreifuss muscular dystrophy (X-EDMD) with cardiac involvement in a four-generation family with a novel mutation in the STA gene. METHODS: Clinical data were provided for 4 affected males and a female carrier. The Western blot analysis of emerin was performed on lymphoblastoid cell lines and followed by sequencing of the emerin gene. RESULTS: A thymine insertion at nucleotide 417 in exon 2, resulting in a frameshift with a premature stop codon at position 62 and absence of functional protein, was found in one of the three available patients. In ten-year-old proband's dizygotic twin-nephews the intermittent first-degree A-V block, atrial and ventricular ectopy, atrial runs, and exit sinus block were found, although the echocardiographic findings were normal. One of the twins also had short episodes of atrial fibrillation, idioventricular rhythm, and junctional rhythm. CONCLUSION: Cardiac abnormalities in the proband's ten-year-old dizygotic twins without evident clinical features suggestive of EDMD were remarkable in contrast to the oldest patient in the family, who lived to the age of 63 without a pacemaker, and to the proband who had a very early onset of muscle wasting and weakness, and a pacemaker implantation at the age of 27. This striking intra-familial variability in cardiac involvement associated with specific null mutation (417 ins T) has practical early diagnostic and possibly preventive implications. It also points at genetic and environmental factors as causes of clinical features in X-EDMD.

Superior sulcus tumor (SST): management at the Institute of Oncology in Ljubljana, Slovenia, 1981-1994.

During the 14-year period under study, 48 patients with SST were treated at the Institute of Oncology in Ljubljana, Slovenia. There were 46 males and two females, aged 29-88 years (median, 60 years). Of 37 cytologically or histologically confirmed tumors, 12 were squamous, eight large-cell, one small-cell, eight adeno, and eight unclassified carcinomas. Performance status (Karnofsky) was assessed as > 90 in eight, 70-90 in 31 and < 70 in nine patients. The duration of symptoms before diagnosis ranged from 1 to 36 months (median, 5 months). All patients had pain, while six also had hemophthysis, 14 Horner's syndrome, and four Horner's syndrome and upper limb paresis. Before the first chest X-ray, 19 patients- were treated for shoulder pain by different specialists. Apical tumor infiltration only on the chest X-ray was found in 13, destruction of the ribs in 31, and destruction of the ribs and vertebral bodies in four patients. Treatment was as follows: radiotherapy in 39 patients (22 with radical, 17 with palliative dose), a combination of surgery and radiotherapy in seven, radiotherapy and chemotherapy in one, and symptomatic therapy alone in one patient. One- and four-year survival of all treated patients was 27% and 11%, respectively. One of the seven patients operated on survived for 44 months, and 2/39 irradiated ones survived for 37 and 56 months, respectively, while others died within 24 months from diagnosis. In 81% of patients the pain was subdued after radiotherapy. The disease-specific survival of all patients included in the follow-up correlated with performance status and M stage, while that of those treated by irradiation alone correlated with tumor dose (P < 0.05).

Postoperative radiotherapy for radically resected N2 non-small-cell lung cancer (NSCLC): randomised clinical study 1988-1992.

In the period 1988-1992, 74 consecutive radically resected patients with NSCLC were randomised to postoperative radiotherapy or surgery alone in order to evaluate the influence of postoperative radiotherapy on survival. There were 61 males and 13 females, aged 35-80 years, median 59 years. Their distribution by stage was as follows: pT1N2 = 19, pT2N2 = 54, pT3N2 = one patient; histology: 32 squamous, 32 adeno and 10 large cell carcinomas; surgery: atypical resection in six, lobectomy in 27, bilobectomy in ten, and pneumonectomy in 31 patients. In 27 patients, only one lymph node in a single mediastinal lymph node site was affected; in 31 patients more than one lymph node in one site; in 16 patients more sites were affected. In 35/74 patients radiotherapy of hilar and mediastinal sites with 3000 cGy in 2 weeks was performed. On December 31, 1994, 19 patients (26%) were still alive; 39/55 patients died of the following causes: locoregional failure-10(26%), distant metastases- 25 (64%), other tumor-unrelated causes-four patients (10%). Five-year survival rates did not show statistically significant differences between the irradiated and surgically treated patients only with respect to sex, pTNM stage, histology and frequency of locoregional failure. The number of metastatic mediastinal lymph nodes was the only significant prognostic factor (P < 0.005) in both randomised groups.

Changes in the properties of honeybee haemolymph alpha-glucosidases following dithiothreitol dissociation of native complexes.

1. The higher relative molecular mass (M(r)) forms of larval honeybee haemolymph alpha-glucosidases are dissociated by dithiothreitol (DTT) into lower M(r) electrophoretic forms, without any important loss of activity. 2. The maximum velocity remains unchanged and the apparent dissociation constant is slightly increased, with Ki approximately equal to 247 mM and I50 approximately equal to 730 mM. 3. By contrast, the major changes affect the Hill coefficient which decreases from 1.0 in controls to 0.7 in presence of 600 mM DTT. 4. In the absence of both DTT and substrate, the major native enzyme form, isolated by gel filtration, spontaneously rearranges to give three additional minor forms, one of lower M(r) and two of higher M(r). 5. These data are consistent with the hypothesis of substrate-directed aggregation of enzyme protomers into functional complexes.

Lethal short limb dwarfism with dysmorphic face, omphalocele and severe ossification defect: Piepkorn syndrome or severe "boomerang dysplasia"?

The authors report a case of lethal neonatal dwarfism characterized by striking micromelia, fused rudimentary and supernumerary digits, large, soft head, pronounced hypertelorism, protruding eyes set laterally, enormous omphalocele and severe deficiency of tubular bone and spine ossification. Histologic examination showed lack of ossification of the cartilaginous anlage of many tubular bones. The cartilage had irregularly distributed chondrocytes. The matrix contained hypocellular and degenerated areas with scattered large chondrocytes. In a few bones a very disorganized growth cartilage was present. The case is similar to that described by Piepkorn et al. (1977) and may represent a severe form of "boomerang dysplasia" (Kozlowski et al., 1981; Tenconi et al., 1983; Kozlowski et al., 1985; Winship et al., 1990).

Management of patients with brain metastases of unknown origin.

During the years 1973-1987, 75 patients were irradiated for brain metastases of unknown origin at the Institute of Oncology in Ljubljana. Of these, 35 (47%) were previously treated by surgery: Metastases were completely removed in 22 patients and partially in 7, whereas biopsy alone was performed in 6 patients. Based on the examinations carried out during radiation therapy and at the time of follow-up, the primary sites of tumor were established as follows: The lung in 40 patients, the breast in 2, melanoma in 2, and the esophagus, kidney, and parotid gland in one patient, respectively. Primary tumor could not be detected in 28 (37%) patients. Metastases were microscopically verified in 48 cases in which anaplastic carcinoma and adenocarcinoma were most frequent. All the patients were irradiated on a cobalt unit, generally with doses of 10 x 300 cGy in 2 weeks. Median survival of the 22 patients with total removal of brain metastases was 9.5 months, one-year survival being achieved in 41% of cases. In the remaining patients median survival was 3 months, whereas only 12% of the patients survived one year. The cause of death were most frequently, i.e. in 45 patients, brain metastases.

[Role of team work in preventing the birth of abnormal children]. / Uloga timskog rada u sprecavanju rodenja nenormalne djece.

In diagnosing and preventing the birth of abnormal children the authors stress the necessity of team work of different specialists and their centralisation at the University complex or hospitals. The results of such a team work organised at the Division of Medical Genetics, Department of Gynecology and Obstetrics in Ljubljana and their experience in detecting some of monogenic, chromosome, and etiologically unknown disorders are presented, as well as the results of the follow-up of certain cases. The value of team work in genetic counselling is also pointed out.

[Trisomy 10q24 leads to 10qter due to a familial translocation t(10;14)(q24;q32) (author's transl)]. / Trisomie 10q24 leads to 10qter par translocation familiale t(10;14)(q24; q32).

The detection of trisomy 10q24 leads to 10qter in a newborn lead to the discovery of a balanced reciprocal t(10;14)(q24;q32) which had been transmitted through four generations. The patient's phenotype corresponds to that already described for trisomy 10q.

[Trisomy 4q26--4qter by t(4;18)(q26;q23)mat translocation]. / Trisomie 4q26--4qter par translocation t(4;18)(q26;q23)mat.

Partial trisomy 4q and perhaps monosomy 8qter was observed in a malformed girl, due to malsegregation of a t(4;18)(q26;q23)mat. Her phenotype was in agreement with the partial trisomy 4q syndrome, and she died 5 months after birth.