Pulmonary Manifestations of Genetic Disorders in Children.

Congenital bronchopulmonary malformations are relatively common and arise during various periods of morphogenesis. Although some are isolated or sporadic occurrences, others may result from single gene mutations or cytogenetic imbalances. Single gene mutations have been identified, which are etiologically related to primary pulmonary hypoplasia, lung segmentation defects as well as pulmonary vascular and lymphatic lesions. Functional defects in cystic fibrosis, primary ciliary dyskinesias, alpha-1-antitrypsin deficiency, and surfactant proteins caused by gene mutations may result in progressive pulmonary disease. This article provides an overview of pediatric pulmonary disease from a genetic perspective.

[Stagewise hybrid method of treating a patient with connective tissue dysplasia, aortic aneurysm, and distal dissection]. / Étapnaia gibridnaia metodika lecheniia bol'nogo s soedinitel'notkannoi displaziei, anevrizmaticheskoi bolezn'iu aorty i distal'nym rassloeniem.

Presented herein is a clinical case report concerning the use of a hybrid technique in stagewise surgical management of a patient with distal dissection and an aneurysm of the thoracoabdominal portion of the aorta. The patient at high risk with the connective tissue dysplasia syndrome had a past medical history of prosthetic repair of the descending thoracic aorta with type-1 haemodynamic correction. Three years later, the findings of computed tomography demonstrated fenestration in the area of the distal anastomosis, a patent false channel, and an increase in the diameter of the unoperated thoracoabdominal portion of the aorta. The first stage consisted in performing prosthetic repair of the infrarenal portion of the aorta by means of the multibranched Coselli thoracoabdominal graft, followed by 'switching' the visceral branches into the formed prosthesis. 14 days later, the second stage included stenting of the dilated suprarenal portion of the aorta. The patient was discharged on day 9 after the second stage of the operation. This clinical case report demonstrates that a hybrid method of treatment may by an alternative to an open operation in high risk surgical patients presenting with severe concomitant somatic pathology.

Aneurysmal disease: thoracic aorta.

Thoracic aortic aneurysms are clinically significant for their high mortality risk in the face of rupture. This article reviews the natural history and pathophysiology of thoracic and thoracoabdominal aortic aneurysms, discusses the evaluation of these patients, and details the treatment options. Specifically discussed are treatment advances arising from the development of endovascular technology.

Congenital contractural arachnodactyly (Beals-Hecht syndrome): a rare connective tissue disorder.

Congenital contractural arachnodactyly (CCA) or Beals-Hecht syndrome (BHS) presents a very rare connective tissue disorder characterized by narrow body habitus, crumpled ears, arachnodactyly, contractures, and scoliosis. In our case report, the physical examination revealed typical physical findings to determine the physical diagnosis of BHS in contrast to negative finding on DNA analysis. From clinical point-of-view, it is important to include a complex clinical approach in making the diagnosis.

Arachnodactyly--a key to diagnosing heritable disorders of connective tissue.

Arachnodactyly literally means spidery fingers, and describes the long, slender fingers typical of patients with Marfan syndrome (MFS). Many clinicians regard arachnodactyly as pathognomonic of MFS; however, this view is misleading as arachnodactyly is a key element of the marfanoid habitus, which is present in several heritable disorders of connective tissue (HDCTs). Other features of the marfanoid habitus include long hands and feet, increased skin stretch, joint hypermobility and characteristic changes in the physiology of the pectum. Here, we focus on the differential diagnosis of diseases with features of the marfanoid habitus. Ectopia lentis (lens dislocation) and aortic root dilation or dissection are cardinal features of MFS. Distinguishing MFS from other HCDTs has important implications for treatment, as cardiovascular and ocular complications commonly seen in patients with MFS are not seen in all HDCTs. Joint hypermobility syndrome and Ehlers-Danlos syndrome are also HDCTs, neither of which is associated with ectopia lentis or aortic changes. Some of the rarer forms of Ehlers-Danlos syndrome are associated with severe vascular, dental and skin pathologies. This Review serves as a guide for correctly diagnosing members of the HDCT family.

[Abdominal vascular structural and functional features in patients with connective tissue dysplasia].

Doppler ultrasound study records decreased volume blood flow in patients with connective tissue dysplasia. Their hemodynamic features are more marked during food testing. Dysplasia-dependent structural changes in the vascular system, such as vascular hypoplasia, wall-occluding lesions, different types of deformities, are one of the causes of lower volumetric blood flow in the abdominal vessels. The found abdominal vascular structural and functional features in patients with connective tissue dysplasia can serve as the basis for blood flow disproportion in different stages of digestion.

Stickler syndrome in Pierre-Robin sequence prenatal ultrasonographic diagnosis and postnatal therapy: two cases report.

The Pierre-Robin Syndrome (PRS) is a rare congenital abnormality, with an approximately 1/30,000 estimated rate, characterized by the presence of the combination of mandibular hypoplasia (micrognathia or small jaw), glossoptosis (retrusion of the tongue into the pharyngeal airway) and, often, a posterior cleft of the secondary palate. It may be an isolated occurrence or part of a more complex syndrome and it is associated with long-term respiratory, nutritional, and developmental difficulties. Stickler syndrome (SS) is a rare autosomal dominant connective tissue disorder estimated to affect approximately 1/7500 newborns. It is diagnosed clinically and, at present, there is no consensus on a minimal clinical diagnostic criterion. The most frequent diagnosis in patients with syndromic Pierre Robin sequence is Stickler syndrome, which may be complicated by congenital high myopia and substantial risk of retinal detachment. However, cases of Stickler syndrome with probable visual complications are rarely identified among this group of patients by members of the cleft team. The patient had an acute unilateral hydrops, with a monolateral keratoconus. The ocular abnormalities included: severe myopia, abnormalities of the vitreous, and high risk of retinal detachment (with subsequent blindness). We report two extremely rare cases of prenatal diagnosis of PRS and SS, prematurely identified by prenatal ultrasonography and successively managed by oculists ophthalmogists.

[Influence of medical rehabilitation under conditions of sanatorium on life quality indices in adolescents with connective tissue dysplasia].

Maximal phenotypic manifestation of connective tissue dysplasia (CTD) is noticed in adolescence. But there are no clear conceptions about efficiency of rehabilitation programs for these patients. Indices of life quality (LQ) of adolescents with CTD, adolescents with CTD and concomitant pathology before and after medical rehabilitation are analyzed in the work. Indices of LQ in healthy children and adolescents with CTD are compared. Life quality is described both by its separated indices and by integral index. Assessment of influence of concomitant pathology in CTD patients on performed treatment is given. It shown that use of complex of physical factors can be considered as high effective method of treatment of young patients with various clinical variants of CTD.

Management of severe cervical kyphosis in a patient with Larsen syndrome. Case report.

Larsen syndrome is a rare genetic disorder of the connective tissue that is characterized by multiple joint dislocations, distinctive deformities of the hands and feet, characteristic facial features, kyphoscoliosis, and segmentation anomalies of the vertebrae. Diverse treatment options, including conservative observation and surgical correction, have been reported for patients who present with cervical spine pathophysiology. Differences in surgical approaches, timing of the correction, and pre- or postoperative bracing have been reported. According to the authors, the present case is the first report of a pediatric patient with Larsen syndrome in whom an asymptomatic cervical instability was treated before neurological deterioration with synchronous anterior decompression and fixation, posterior fusion and fixation, and halo placement. A review of the literature on similar patients reveals the variety of practices associated with a diagnosis of Larsen syndrome.

Dysplasia of C-1 and craniocervical instability in patients with Shprintzen-Goldberg syndrome. Case report and review of the literature.

Shprintzen-Goldberg syndrome is a rare connective tissue disorder characterized by marfanoid habitus and additional dysmorphic stigmata. Craniocervical anomalies occur in fewer than 30% of cases. Serious vertebral instability can also occur, albeit rarely. The authors report on the first patient treated with surgical fusion at the craniocervical junction because of a C-1 dysplasia and severe instability. The skeletal and cardiovascular anomalies that can pose additional problems for surgical treatment and perioperative care are discussed in detail.

[Rupture of the major artery in incomplete desmogenesis].

A pathomorphological examination of a congenital disease - incomplete desmogenesis (ID) - was made in 5 women aged 19-34 years. They had spontaneous ruptures of the major arteries (subclavial, brachial, splenic, gastric). Microscopically, the wall of the ruptured artery contained no or minimal collagenic structures which looked homogeously, like a mixomatous edema. Content of acid mucopolysaccharides and hyperelastoses was elevated. The rupture was provoked by infections, additional loads, such as pregnancy, etc. Vascular surgery in ID is difficult as arteries often break at suturing while vascular walls are amputated at ligation. In one patient tamponade stopped hemorrhage and saved her.

Imaging of the pediatric hand: soft tissue abnormalities.

This review attempts to demonstrate the spectrum of soft tissue masses encountered in the child's hand. The diagnosis may be suggested by the combination of physical exam and radiographs. Frequently the etiology of a soft tissue mass cannot be established by conventional radiographs and further imaging is necessary. MRI by virtue of its ability to provide detailed soft tissue characterization is the preferred method of imaging the problematic soft tissue mass.

Tumour necrosis factor alpha, lipid peroxidation and NO* are increased and associated with decreased free-radical scavenging enzymes in patients with Weill-Marchesani syndrome.

AIM: Weill-Marchesani syndrome (WMS) is a rare systemic disorder with both autosomal recessive and dominant inheritances. Accumulation of reactive oxygen species such as O2*-, H2O2 and OH* causes lipid peroxidation (LPO), whereas antioxidant enzymes (superoxide dismutase (SOD), glutathione peroxidase (GSHPx)) mediate defence against oxidative stress. Excess tumour necrosis factor (TNF)-alpha and NO* react with O2*- and cause further antioxidant depletion with an increase in mutation frequency by H2O2. This study investigated the levels of SOD, GSHPx, catalase (CAT), TNF-alpha, NO and LPO in patients with WMS. METHODS: A group of 10 WMS patients (four males, six females; age, 26.5+/-19.0 years) and 10 age-matched and sex-matched controls (five males, five females; age, 27.3+/-18.2 years) were included. Serum TNF-alpha levels were determined by a spectrophotometer technique using immulite chemiluminescent immunometric assay. Malondialdehyde (MDA) was determined in plasma; CAT in red blood cells (RBCs), and SOD and GSHPx in both plasma and RBCs. Total serum NO* levels were evaluated by Griess reaction. RESULTS: Mean levels of TNF-alpha (8.3+/-0.6 pg/ml) in WMS patients were significantly (p<0.001) higher than controls (4.3+/-0.2 pg/ml). Plasma MDA levels in patients and controls were 5.4+/-0.8 and 1.8+/-0.6 micromol/l, respectively, and the difference was significant (p=0.0002). SOD and GSHPx activities were significantly lower in both RBCs and plasma of WMS than in controls (RBC-SOD, 3981.9+/-626.6 versus 5261.6+/-523.0 U/g haemoglobin (Hb), p=0.0005; plasma-SOD, 529.4+/-49.3 versus 713.4+/-55.7 U/g protein, p=0.0002; RBC-GSHPx, 682.7+/-42.0 versus 756.5+/-47.6 U/g Hb, p=0.0011; plasma-GSHPx, 107.3+/-15.0 versus 131.4+/-19.7 U/g protein, p=0.0113). In addition, serum NO (NO*-2 + NO*-3) levels were also significantly (p = 0.0002) increased in WMS patients (54.4+/-5.7 versus 26.9+/-6.7 micromol/l). RBC-CAT levels were similar between groups (125.6+/-21.3 versus 131.0+/-21.5 k/g Hb, p = 0.8798). CONCLUSIONS: The elevated LPO, TNF-alpha and NO* with decreased antioxidant enzyme activities indicated impaired antioxidative defence mechanisms with an oxidative injury and cell toxicity in WMS patients. The use of multiple antioxidants and free radical scavengers might be helpful in this genetic disorder.

[Extracardiac manifestations of undifferentiated connective tissue dysplasia]. / Vnekardial'nye proiavleniia nedifferentsirovannoi displazii soedinitel'noi tkani.

Undifferentiated connective tissue dysplasia (UDCTD) is a common type of congenital mesenchymal defect. Among the visceral manifestations of UDCTD, cardiac anomalies have been studied in detail while the nature, extent, and clinical significance of changes in other viscera are much less known. The review summaries data on currently accepted extracardiac manifestations of UDCTD, such as venous insufficiency, tracheobronchial dyskinesia, nephroptosis, genital prolapse, gastrointestinal disorders, hemostatic pathology.

Camptodactyly, arthropathy, coxa vara, and pericarditis syndrome among egyptians.

OBJECTIVE: To highlight the clinical, radiological, and pathological presentations of 10 Egyptian patients with camptodactyly, arthropathy, coxa vara, and pericarditis (CACP) syndrome. Methods. Ten cases underwent a full history, complete clinical examination, laboratory and radiological investigations (and magnetic resonance imaging, MRI, of knee joints); arthroscopic histopathological synovial studies were performed in 6 cases. Results. Camptodactyly and large joint arthropathies were present in all cases. The onset was at birth in 5 cases, and consanguinity was present in all cases. Laboratory investigations were normal in all cases (normal complete blood cell count, erythrocyte sedimentation rate, absent rheumatoid factor, and antinuclear antibody). Synovial fluid analyses were acellular in 3, hypocellular in 4, and moderately cellular in 2 cases. Histopathology revealed noninflammatory synovial hyperplasia in the 6 synovial biopsies obtained, with multinucleated giant cells in 4 of them. Plain hip radiology revealed short broad femoral neck and widening of joint space in all cases, with coxa vara in 9 cases. MRI of the knees showed rim-like enhancement of the lining of the fluid filled bursae in 7 cases, and homogenous enhancement pattern in 2 cases. No evident cartilage destruction existed in any case. CONCLUSION: Our cases represent a familial syndrome of noninflammatory arthropathies associated with camptodactyly and coxa vara. The complete picture of the syndrome may be related to disease duration, and MRI is a useful tool in diagnosis. Physicians should be aware of the syndrome, to avoid misdiagnosis with other pediatric connective tissue diseases.

General anaesthesia in a child with Larsen syndrome.

Larsen syndrome is a rare congenital connective tissue disorder which is characterized by multiple dislocations of major joints, typical facial appearance, cervical spine narrowing and instability and respiratory difficulties secondary to laryngotracheomalacia. A case of general anaesthesia for laparoscopic hernia repair in a male child aged 16 months with this syndrome is presented. Anaesthesia was well tolerated though intubation proved difficult. Cervical spine instability and postoperative respiratory complications are potential problems.

Ciliary body is not hyperplastic in Weill-Marchesani syndrome.

PURPOSE: To demonstrate the in-vivo morphology of the ciliary body in Weill-Marchesani syndrome which might be of pathophysiological importance for the spherical shape of the crystalline lens. METHODS: Three juvenile patients with Marchesani syndrome were examined by ultrasound biomicroscopy of the anterior segment. RESULTS: The in-vivo configuration of the ciliary body in these Weill-Marchesani patients with normal axial length of the eye showed no signs of hyperplasia, and was even relatively small. CONCLUSION: Spherophakia and hyperplasia of the ciliary body are not necessarily associated with the syndrome, as supposed by Marchesani and other investigators. Instead, spherophakia might be regularly accompanied by a small ciliary body in Weill-Marchesani syndrome.

Congenital plate-like osteoma cutis of the forehead: an atypical presentation form.

Cutaneous ossifications or osteoma cutis can be found in many syndromes. Primary osteoma cutis, present since birth or the first months of life, in the absence of metabolic disorders or trauma, is found in congenital plate-like osteoma cutis and progressive osseous heteroplasia, coexisting in the latter with deep connective tissue ossifications. This report documents the case of a 7-year-old female with a plate-like cutaneous ossification of the forehead causing aesthetic deformities. Other dermal ossifications in the inguinal and preauricular region, as well as the left hand and a small focus in the extraocular muscles of the left orbit, were also present. These lesions did not show progression, and most of them were present since birth. The lesion of forehead was treated surgically. The lack of progression and the fact that the orbital lesion was solitary still fits the criteria for the diagnosis of plate-like osteoma cutis. Plate-like osteoma cutis and progressive osseous heteroplasia may represent varieties of the same disorder.