Polymorphisms associated with low bone mass and high risk of atraumatic fracture.

Osteoporosis is a serious disease characterized by high morbidity and mortality due to atraumatic fractures. In the pathogenesis of osteoporosis, except environment and internal factors, such as hormonal imbalance and genetic background, are also in play. In this study candidate genes for osteoporosis were classified according to metabolic or hormonal pathways, which regulate bone mineral density and bone quality (estrogen, RANKL/RANK/OPG axis, mevalonate, the canonical circuit and genes regulating the vitamin D system). COL1A1 and/or COL1A2 genes, which encode formation of the procollagen 1 molecule, were also studied. Mutations in these genes are well-known causes of the inborn disease 'osteogenesis imperfecta'. In addition to this, polymorphisms in COL1A1 and/or COL1A2 have been found to be associated with parameters of bone quality in adult subjects. The authors discuss the perspectives for the practical utilization of pharmacogenetics (identification of single candidate genes using PCR) and pharmacogenomics (using genome wide association studies (GWAS) to choose optimal treatment for osteoporosis). Potential predictors of antiresorptive therapy efficacy include the following well established genes: ER, FDPS, Cyp19A1, VDR, Col1A1, and Col1A2, as well as the gene for the canonical (Wnt) pathway. Unfortunately, the positive outcomes seen in most association studies have not been confirmed by other researchers. The controversial results could be explained by the use of different methodological approaches in individual studies (different sample size, homogeneity of investigated groups, ethnic differences, or linkage disequilibrium between genes). The key pitfall of association studies is the low variability (7-10 %) of bone phenotypes associated with the investigated genes. Nevertheless, the identification of new genes and the verification of their association with bone density and/or quality (using both PCR and GWAS), remain a great challenge in the optimal prevention and treatment of osteoporosis.

Hajdu-Cheney syndrome: report of a family and a short literature review.

We report three members of an Armenian family with Hajdu-Cheney syndrome. The history suggested that five other members of the family were also probably affected. This disorder is important for the radiologist because distinctive radiographic findings make the diagnosis possible before clinical signs and symptoms are fully developed. Additionally, radiographic examination is essential in all patients suspected of Hajdu-Cheney syndrome for confirmation of the clinical diagnosis. Radiographic examination also detects complications of the syndrome not evident on clinical examination.

Czech dysplasia metatarsal type.

We report three further patients of the recently described new bone dysplasia-dominantly inherited pseudorheumatoid arthritis. The patients of this report have a similar clinical history, the same distinctive phenotype and almost identical radiographic findings. The only major difference is absence of weather dependent articular pain which characterized the family of the previous study. This report expands the clinical data of this bone dysplasia. All patients are Caucasians and originate from different parts of the Czech Republic. It seems that this disorder is quite a common constitutional bone disorder in this country. We propose the name of Czech Dysplasia Metatarsal Type for this unique disease.

3-M syndrome in two sisters.

3-M syndrome is a rare, autosomal recessive dwarfing syndrome characterized by prenatal growth restriction, facial dysmorphism and absence of both microcephaly and mental retardation. The term 3-M syndrome originates from the common initial of the first three authors of the first report. The diagnosis is established by a combination of clinical history, clinical examination and radiographic findings. The present report shows two sisters whose facial features were slightly different from those usually reported. In addition, they presented with small nails and abnormal dermatoglyphics. The present report expands the phenotypic spectrum of 3-M syndrome.

Poland-Möbius syndrome and disruption spectrum affecting the face and extremities: a review paper and presentation of five cases.

The author summarizes hitherto assembled experience with the clinical and genetic characteristics of Poland's and Möbius syndrome. Five selected case-records with this disease and the sequence of the Poland-Möbius syndrome are presented. Another case-record is devoted to an allied syndrome, hypoglossia-hypodactyly, found in a spontaneously aborted fetus. For establishment of a more accurate symptomatology, an irreplaceable place is held by anthropometric examination; for objectifying the asymmetry of the chest the so-called cyrtogram, the chest circumference recorded by means of a wire, is valuable. From the aspect of genetic counseling, preconception care is always provided to mothers from families with reproductive intentions, as well as ultrasonographic examination of the fetus in areas of assumed acral symptomatology (signaling phenotype). In two families ultrasonography was used for prenatal diagnosis. Invasive prenatal diagnosis by amniocentesis was employed in a family with Möbius syndrome. In these families dermatoglyphs have certain common characteristics, such a tendency towards simple patterns. In the wider family of one of our patients we detected in a cousin Parkes-Weber-Klippel-Trenaunay's syndrome, which may indicate common vascular predisposing factors.

[An unusual case of primary hyperparathyroidism in a woman with Gorlin-Goltz syndrome]. / Neobvyklý prípad primární hyperparatyreózy u nemocné se syndromem Gorlina-Goltze.

Nevoid basal cell carcinoma syndrome (NBCCS) has been known to coincide with different forms of other neoplasias; however, parathyroid adenoma in this syndrome has not previously been described. The authors report a case of such association in a 50-year old white woman. The adenoma was verified before operation by biochemical, isotopic and cytologic methods and later, after the excision of adenoma, histologically.

Precision grip with congenital hypoplasty or hypofunction of the thumb.

We tested the grip in four patients with congenital defects of the hand and either a hypoplastic thumb or a thumb with impaired inervation. Small objects were taken by a scissors grip between the fingers. In a hand with radial duction in the manus vara congenita, during strengthening of the wrist, the grip from the ulnar side between the fourth and fifth fingers was changed to the radial side between the second and third fingers. Large objects were gripped by all the three-phalanx fingers into the palm in a horizontal position. In case 4 with hypoplasia of the thumb grade IIIC by the classification of Blauth and Buck-Gramcko, we describe a transposition of the index finger to the site of the thumb and the hypoplastic thumb to the site of the index finger. It is obvious that the precision grip is affected by the thumb length and strengthening of the ulnar side of the wrist. We assume that the scissors grip is the earliest precision grip in the evolution of the primate hand.

Origin of nondisjunction in trisomy 8 and trisomy 8 mosaicism.

Causes of chromosomal nondisjunction is one of the remaining unanswered questions in human genetics. In order to increase our understanding of the mechanisms underlying nondisjunction we have performed a molecular study on trisomy 8 and trisomy 8 mosaicism. We report the results on analyses of 26 probands (and parents) using 19 microsatellite DNA markers mapping along the length of chromosome 8. The 26 cases represented 20 live births, four spontaneous abortions, and two prenatal diagnoses (CVS). The results of the nondisjunction studies show that 20 cases (13 maternal, 7 paternal) were probably due to mitotic (postzygotic) duplication as reduction to homozygosity of all informative markers was observed and as no third allele was ever detected. Only two cases from spontaneous abortions were due to maternal meiotic nondisjunction. In four cases we were not able to detect the extra chromosome due to a low level of mosaicism. These results are in contrast to the common autosomal trisomies (including mosaics), where the majority of cases are due to errors in maternal meiosis.

[Arthrogryposis multiplex congenita. I.]. / Arthrogryposis multiplex congenita.

In part I the authors deal with the present possibilities of the diagnostics and therapy of arthrogryposis multiplex congenita. They proceed from the classification after Hall of 1982 (classification of the so-called distal arthrogryposis) and of 1983 where congenital contractures are divided into three groups according to associated system anomalies. On the basis of their own experience they deal in details with distal arthrogryposis - amyoplasia which differs from spinal degenerative diseases by 3 symptoms: 1. it does not deteriorate after the birth, 2. nerves are not affected, 3. intelligence is normal. Differential diagnostics is carried out on the basis of clinical-genetic examination. Dermatoglyphic examination contributes to an early diagnosis mainly in distal arthrogryposis. The seriousness of neurogenic or myogenetic affection is determined by EMG examination. The authors compare therapeutical literary aspects with their own methods of treatment. The evaluation of diagnostic and therapeutical results is presented in part II of the communication. Key words: arthrogryposis multiplex congenita, amyoplasia, distal arhtrogryposis, electromyography, dermatoglyphes, surgical treatment.

[Arthrogryposis Multiplex Congenita - Part II.]. / Arthrogryposis multiplex congenita (2. cást).

It is a follow-up to Part I of the communication where the authors report on the present possibilities of the diagnostics and therapy of arthrogryposis multiplex congenita. In evaluating the patients with congenital contractures they proceed from the classification of Hall et al. of 1982 and 1983. A 24-member group is made up of patients with classic and distal arthrogryposis. The diagnostics is based on the clinical-genetical examination including dermatoglyphical and electromyographical examination. Electromyographical examination aims at the determination of the prognosis and impairment of mobility. EMG examination has proved neurogenic lesion in 17 children and myogenic lesion which was combined with neurogenic lesion in 3 children. After repeating EMG examination the authors found out in 5 children out of 6 the progression of neurogenic lesion. Dermatoglyphical examination performed in 13 patients (with taking sole prints in four of them) showed considerable changes which are significant for arthrogryposis. In evaluating the clinical findings the verticality of the course of papillary lines correlates with the degree of the clinical impairment as well as the increase of atdangles. The surgical treatment of contractures of lower extremities is indicated on the basis of the authors' own experience as early as in the first year of life. The result of the therapy is to a decisive extent influenced - apart from the severity of congenital contractures - by the timely and longterm comprehensive treatment carried out by an orthopaedic surgeon and rehabilitation specialist closely cooperating together and in case of occurrence of other associated congenital defects also by other specialists. Adequate involvement of parents is a necessary condition for a successful treatment. Key words: arthrogryposis multiplex congenita, amyoplasia, distal arthrogryposis, electromyography, dermatoglyphes, therapy.

[Flexional adduction contracture of the thumbs in distal arthrogryposis type I.]. / Flekcne addukcní kontraktura palcu rukou u distální artrogrypózy typu I.

The authors discuss diagnostic and therapeutic aspects of flexion adduction contractures of the thumb - so-called congenital clasped thumb - in patient with distal arthrogryposis type I. The diagnosis is based on classification of distal arthrogryposis elaborated by Hall et al. in 1982. For the prognosis of the deformity and strategy of treatment it is an advantage to divide congenital clasped thumb (CCT) into four groups, as recommended by Weckesser et al. in 1968. The demonstrated patient belongs according to the mentioned criteria into group 2. Associated congenital developmental defects were dealt with in preschool age - a tracheal cyst, inguinal hernias, cryptorchism. Orthopaedic treatment extended over a long period (from 3 months to 12 years); the surgical operations were performed in several stages. The very satisfactory functional results or the reconstruction operations of the hands could not be expressed objectively by EMG examination of the thenar musculature due to hypotrophy and a fixed flexion adduction contracture. Repeated EMG examinations of selected muscles of the upper and lower extremity revealed progression of a neurogenic lesion. An important dermatoglyphic finding was the vertical course of the main papillary lines, the monkey line of the palms and absence of flexional lines of the fingers. Key words: flexion adduction contracture of the thumbs, congenital clasped thumb, distal arthrogryposis, surgery of the hand, electromyography, dermatoglyphs.

Dermatoglyphics in juvenile hypertension.

Dermatoglyphics of 172 children and young adults (116 males, 56 females) with hypertension, 13-27 years old, were compared with those of 130 healthy male and 110 female controls. Several differences were observed between the two groups. Hypertensive patients had a somewhat lower frequency of fingertip ulnar loops, higher frequency whorls and a higher total finger ridge count. They also had a somewhat higher mean atd angle, significantly more frequent distal position of the axial triradius (mostly in t' position) and more missing axial triradii compared to controls. The differences between a-b ridge counts, the interdigital, thenar and hypothenar patterns were generally small and sometimes limited to one sex or one hand only. The observed differences seem to indicate a genetic influence in the etiology of essential hypertension.

[Dermatoglyphic characteristics of the Czech population]. / Dermatoglyfické charakteristiky ceské populace.

Statistical processing of results obtained from dermatoglyphic digital patterns of the Czech population--110 women and 130 men of a reference group--revealed the tendency of more complex pattern formation in men and a tendency of simple pattern formation in women. As regards the frequency of vortices, the differences are significant at the 1% level (in men they form 24.15% patterns, while in women 14.27%). There is also a significant difference in the ratio of arches (1% level of significance)--frequency in men, 5.85%, is lower than in women--11.69%. In the general evaluation the ulnar loops differ only at the 5% level of significance (in men 58.85% and in women 63.18%). The frequency of radial loops and double loops differ insignificantly. The results indicate a greater trend of asymmetrical patterns in men than in women. In investigations of the sexual dimorphism the attained numbers of statistical differences differ by fingers--the most widely different values are recorded in the index fingers and the least different ones in the middle fingers. The number of statistical differences by sex differs also by patterns: most in vortices and arches and least in double loops.

[Ectodermal dysplasia with alopecia, a higher rate of chromosome breaks and normal dentition]. / Ektodermální dysplázie s alopecií, vyssí frekvencí chromosomových zlomu a normální denticí.

The authors present in two case-histories of unrelated female patients the characteristics of the syndrome of ectodermal dysplasia with alopecia and absence of hair and concurrent immunodeficiency and a higher number of chromosomal breaks. In the probands some other important symptoms of ectodermal dysplasias were lacking, such as disorders of dentition and absence of sweat glands. In this affection, hitherto not mentioned in our literature in conjunction with an increased number of chromosomal breaks, the author draws attention to genetic and prenatal genetic associations. He assumes an autosomal recessive heredity of this nosological unit.

[Clinical and genetic characteristics of the Klippel-Trenaunay syndrome]. / Klinická a genetická charakteristika syndromu Klippel-Trenaunay.

The authors examined comprehensively a group of 23 patients with angiodysplastic changes of the type of Klippel-Trenaunay's syndrome. It is a longitudinal investigation, incl. a paediatric and genetic examination. The authors recorded the main phenotypical characteristics of the disease with emphasis on biomechanical aspects. The genealogical examination revealed microsymptoms in the family in a total of 52.2%, such as varicose veins and crural ulcers, haemangiomas and congenital heart disease. The genetic examination proves the assumed polygenic type of heredity with a low risk for grade 1 relatives, i.e. children and siblings of the affected subjects, who are isolated cases in the pedigree. In rare instances the authors recorded complete transmission in two generations. The clinical picture of the disease involves above all hemihypertrophy or asymmetry ensuing from trophic changes, mainly of the extremities and adequate part of the trunk. These changes were recorded in 100% of the investigated patients. Usually the lower half of the body is affected--52.2%, a lateral predilection was not observed. The authors mention also other facultative characteristics of the syndrome.

[The ADAM syndrome]. / Syndrom ADAM.

The author demonstrates genetic counseling and prenatal diagnosis in a family where a severely malformed infant was born with the diagnosis of the syndrome of multiple animal malformations and mutilations. These disorders are known under the acronym ADAM (amnial deformation, adhesion, mutilation). Based on the case-history the author explains the possibility to apply prenatal diagnostic methods and makes comparisons with similar cases in the literature.

[Deviations in dermatoglyphic signs in juvenile hypertensives]. / Odchylky dermatoglyfických znaku u juvenilních hypertoniku.

In 172 children and young adults aged 13-27 years dermatoglyphic deviations were investigated, as compared with the normal Prague population. The authors tested 116 hypertonic males, as compared with 130 male controls; 110 healthy women were compared with 56 suffering from hypertension. Using classical modern statistical tests, some significant deviations were found in the pathological groups. The authors detected a less frequent prevalence of ulnar loops and more frequent whirls on the fingers of hypertensive patients. The numbers of papillary lines on the fingers were higher, as compared with normal values. Higher "atd" values, although not significantly, were found a more frequent incidence of distal positions of the axial triradius. Deviations of some other signs on the palms such as the number of lines between triradii a and b, patterns in the interdigital spaces, on the hypothenar and thenar were less marked and there were moreover sex-conditioned differences. The observed changes suggest a marked participation of genetic factors in the aetiology of essential hypertension and they can be explained by laws of developmental mechanics of the papillary lines during embryogenesis. Dermatoglyphs, a non-invasive method, could serve as a screening indicator for the follow up of individuals in threatened families.