Percutaneous treatment of a ruptured superior mesenteric artery aneurysm in a child

Splanchnic artery aneurysms are very rare in children. We report a 10-year-old girl with a large atraumatic ruptured superior mesenteric artery aneurysm that was considered inoperable. She was ultimately treated with two percutaneous US-guided thrombin injections, which led to complete occlusion of the aneurysm. The aetiology of the aneurysm remained unclear, but a family history was suggestive of a congenital connective tissue disease such as Ehlers-Danlos syndrome subtype IV.     

Arterial tortuosity syndrome

The arterial tortuosity syndrome is a rare congenital disorder characterized by elongation and generalized tortuosity of the major arteries including the aorta. Associated clinical features consist of excessively stretchable skin and joint laxity which is indicative of a connective tissue disorder such as Ehlers-Danlos or Cutis laxa syndrome. The gene locus of the arterial tortuosity syndrome has recently been localised on chromosome 20q13; inheritance ist autosomal recessive. - We report on a newborn with arterial tortuosity syndrome and hiatal hernia, bilateral hip dislocation, inguinal hernias and diffuse tortuosity of the great arteries including the aorta. Known gene loci involved in Ehlers-Danlos syndrome, cutis laxa syndrome and other connective tissue disorders were excluded by specific DNA markers. By homozygosity mapping with polymorphic microsatellite markers it was possible to confirm the gene locus for the ATS on chromosome 20q13. In addition to the presentation of this patient, a review of the literature is presented.     

Adrenocortical function in children with connective tissue syndromes and funnel chest deformation

Measurement of the content of C-21-corticosteroids in the diurnal urine by thin-layer chromatography has demonstrated that in children with isolated and syndromal forms of funnel-like chest deformation, grades II and III, adrenocortical function is decreased. In preschool children, such a decrease is accompanied by proneness to the tense biosynthesis of glucocorticoids. Children with congenital hereditary connective syndromes manifest adrenocortical dysfunction, most characteristic of Marfan's syndrome, and, to a less degree, of Ehlers-Danlos syndrome and unclassified complex of developmental defects with the Marfan-like phenotype. In view of this fact, the children with Marfan's, Ehlers-Danlos syndromes and with the unclassified complex of developmental defects with the Marfan-like phenotype and children with funnel-like chest deformation, grades II and III, should be given glucocorticoid hormones in stressful conditions (severe diseases, traumas, operations).     

The clinical spectrum of congenital contractural arachnodactyly

A case of congenital contractural arachnodactyly with severe cardiovascular malformations is described. This case and two other reports of CCA with congenital heart disease from the literature indicate a wider spectrum of clinical manifestations in CCA than generally assumed. The pattern of abnormalities suggests that the underlying connective tissue abnormality in CCA is “spotty” and not generalized as in such disorders as the Marfan syndrome, Stickler syndrome and arthro-dento-osteo dysplasia.     

A new type of Ehlers-Danlos syndrome associated with tortuous systemic arteries in a large kindred from Qatar

AIM: To describe the clinical spectrum of anomalies of a new type of Ehlers-Danlos syndrome in 32 patients from a large inter-related extended family in Qatar. METHODS: Among the 32 patients (from 22 families), there were 6 affected pairs of siblings and 2 families with 3 affected siblings. The male to female ratio was 2:1, ages ranging from birth to 18 y (mean 7.4 y). RESULTS: Anomalies included a variable degree of skin hyperextensibility, hypermobility of small and large joints, and tortuous systemic arteries. Peculiar facial features included epicanthic folds, flat saggy cheeks, elongated faces and micrognathia. The combination of an elongated aortic arch and tortuous brachiocephalic arteries was seen in 30 patients (93.8%), aneurysm of the ascending aorta in 3 patients (9.4%), bifid pulmonary artery in 27 patients (84.4%) and multiple severe peripheral stenosis of the right and/or left pulmonary artery in 7 patients (21.9%). A prominent aortic knuckle was observed on the chest roentgenograms of 30 patients (93.8%); inguinal hernia in 11 patients (34%), diaphragmatic hernia and/or hiatus hernia in 7 patients (21.9%); and laryngo-tracheomalacia in 2 patients (6.3%). Generalized muscle hypotonia was found in 15 neonates (46.9%). Parental consanguinity involved in all the patients was traced to a common ancestor from a large Bedouin tribe in Qatar. These patients are at risk for potentially catastrophic arterial rupture. Linkage to the major loci involved in Ehlers-Danlos syndrome and other connective tissue disorders, such as Cutis Laxa, Familial Aneurysm, and Osteogenesis imperfecta, was excluded by using specific DNA markers, confirming the uniqueness of this disorder. CONCLUSION: The study describes a large cohort of patients from the same closely related family, sharing peculiar dysmorphisim and consistent radiological and echocardiographic features different from known types of Ehlers-Danlos syndrome. As known loci involved in Ehlers-Danlos syndrome and other connective tissue disorders were excluded by specific DNA markers, this appears to be a new type of Ehlers-Danlos syndrome or even a new syndrome.     

Ehlers-Danlos syndrome type VI with cystic malformations of the meninges in a 7-year-old girl

A 7-year-old girl with thoracolumbar kyphoscoliosis was admitted for further diagnostic evaluation after a spinal MRI scan had shown several intraspinal extramedullary lesions. The clinical features including joint hypermobility and cigarette-paper like scars led to the presumptive diagnosis of Ehlers-Danlos syndrome type VI (EDS VI). Analysis of urinary lysyl- and hydroxylysyl-pyridinoline cross-links excretion confirmed a deficiency of lysylhydroxylase 1 and the diagnosis of EDS VIA. Findings on the spinal MRI scan were interpreted as spinal meningeal cysts. Over a period of 2 years, the patient developed no neurological deficits and no radiological signs of progression of the spinal lesions. Conclusion: we assume cystic malformations of the meninges to be most likely the result of connective tissue weakness in Ehlers-Danlos syndrome type VI.Abbreviations EDS Ehlers-Danlos syndrome - EDS VI Ehlers-Danlos syndrome type VIDedicated to the 65th birthday of Professor Jürgen Kunze     

Thrombocytopenia and severe hyperbilirubinemia in the neonatal period secondary to congenital thrombotic thrombocytopenic purpura and ADAMTS13 deficiency

Congenital thrombotic thrombocytopenic purpura (TTP) is an inherited form of TTP due to the deficiency of von Willebrand factor (vWF) cleaving protease ADAMTS13. The authors describe two children with congenital TTP who presented with thrombocytopenia, hemolytic anemia, elevated LDH levels, and schistocytes on peripheral blood smear. In both children, the diagnosis of the disease was delayed despite neonatal histories significant for thrombocytopenia, anemia, and severe hyperbilirubinemia. Severely decreased ADAMTS13 activity (<0.1 U/mL), the absence of an inhibitor to the protease, and partial deficiency found in the parents confirmed the diagnosis of congenital TTP. The authors suggest that congenital TTP should be considered in the differential diagnosis for newborns presenting with severe hyperbilirubinemia, anemia, and thrombocytopenia.     

Collagen maturation defects in Ehlers-Danlos keratopathy

Ehlers-Danlos syndrome is one of many inherited abnormalities of connective tissue, specifically collagen. A 16-year-old caucasian female with Type VI Ehlers-Danlos syndrome had five unusual corneal findings, four of which have not been reported in association with Ehlers-Danlos syndrome: micro-cornea (previously reported), cornea plana, keratoconus posticus, stromal haze at the level of Bowman's layer and a peripheral ring opacity suggestive of anterior embryotoxon. Type VI Ehlers-Danlos syndrome is associated with deficient activity of lysyl hydroxylase which ultimately is responsible for cross-linking collagen chains, the source of its tensile strength. Genetic regulation of procollagen formation is believed to be mediated by mRNA. Aggregation and maturation in the extracellular matrix is probably influenced and mediated by its evolving biochemical environment, particularly by complex carbohydrate moieties. An understanding of collagen maturation, and the pathophysiologic and biophysical consequences of abnormalities at this level of biochemical organization, permits more specific understanding of ocular dysmorphology and collagen diseases.     

Acute parvovirus B19 infection mimicking congenital dyserythropoietic anemia

Infection with human parvovirus B19 is known to cause transient erythroid aplasia in children with hemolytic anemia but has also been associated with bone marrow necrosis and morphologic changes suggesting myelodysplasia. The authors describe a previously healthy child who presented with severe hypoplastic anemia. Initial bone marrow aspiration revealed erythroid hyperplasia, dyserythropoiesis, and multinucleated erythroid cells with nuclear budding and bridging, consistent with the diagnosis of congenital dyserythropoietic anemia. Serologic testing documented acute parvovirus infection, and on recovery the correct diagnosis of unsuspected congenital spherocytosis was established. This case expands the spectrum of hematologic disease associated with acute parvovirus infection.     

Medulloblastoma as a first presentation of fanconi anemia

Fanconi anemia is a chromosomal instability syndrome associated with certain congenital abnormalities, defective hemopoiesis, and an increased risk of developing acute myeloid leukemia and some solid tumors. The diagnosis can be made at birth if congenital abnormalities are present but is often made in childhood when hematologic complications develop. The authors report a case of Fanconi anemia diagnosed in a child with no congenital abnormalities and normal bone marrow who first presented with a cerebellar medulloblastoma. The authors discuss diagnostic and therapeutic implications for such malignancies in Fanconi anemia.     

Systemic diseases and the lung

Systemic diseases affecting the lung are fortunately relatively rare in paediatric practice. A number of conditions do, however, cause significant respiratory complications, which can result in serious morbidity and mortality in this age group. These include connective tissue disorders such as systemic lupus erythematosus, dermatomyositis and scleroderma, inherited connective tissue disorders such as Ehlers-Danlos and Marfan's syndrome, lysosomal storage disorders such as mucopolysaccharidoses, familial dysautonomia, Langerhans cell histocytosis, pulmonary lymphangiomatosis, sarcoidosis and sickle cell disease. The investigations of these conditions are often complex but form part of the overall multisystem review of each individual patient. Treatment is individualised but often requires the extended use of corticosteroids and other immunosuppressants. The outcome is variable and depends on the ability to control the underlying condition. Long-term chronic lung damage is not unusual and these diseases, when they affect the lung, carry a small but significant mortality.     

Rupture of a renal artery aneurysm. Fulminant course, fatal complication of type IV Ehlers-Danlos syndrome in childhood]

A 12 year old girl with joint laxity, hyperelastic and vulnerable skin and tall stature was labeled as "Marfan syndrome". She died unexpectedly from a ruptured aneurysm of the right renal artery. All these features are typical for Ehlers-Danlos syndrome type IV. The diagnostic difficulties and the classification of connective tissue disorders are discussed and further possible complications are reviewed from the literature. The importance of an exact diagnosis is stressed in order to assess the prognosis and start possible therapeutic measures as early as possible.     

Bruck syndrome: neonatal presentation and natural course in three patients

Three unrelated patients with congenital arthrogryposis and brittle bones, the main neonatal signs of Bruck syndrome, are presented. In infancy and early childhood recurrent fractures of ribs and long bones and persistent Wormian bones in the calvarium are reminiscent of osteogenesis imperfecta (OI) even with white sclerae, normal dental quality and normal hearing as important clinical negatives. The diagnosis was made before two years of age in two, and in adolescence in the third patient. The latter's radiologically documented long-term natural course reveals slow progressivity of osteopenia and growth deficiency, worsening tendon contractures and pterygia in addition to increasing spine and pelvis deformation. Mental development remains normal. Bruck syndrome is monogenic and probably due to homozygosity of an as yet unidentified gene. As no alteration in the collagens I and III is detected and molecular screening reveals no mutation in the COL1A1 and COL1A2 genes, the pathogenesis of this severe disorder of connective tissue remains largely unknown. Received/accepted: 6 May 1998     

HEMOGLOBIN-BASED OXYGEN CARRIERS: A Long Road from Bench to Bedside

Congenital syphilis is a rare, serious disease that continues to be a major health-care problem. The infected neonate may be asymptomatic or multiple-organ system involvement may occur. Anemia and thrombocytopenia are common hematological findings. Hemophagocytic lymphohistiocytosis (HLH) is a clinicopathological condition characterized by activation and uncontrolled nonmalignant proliferation of T lymphocytes and macrophages. The authors report an infant with congenital syphilis as a very rare cause of hemophagocytic syndrome. The reason for anemia and thrombocytopenia in congenital syphilis is not clear. The authors suggest that hemophagocytosis may play role in pathogenesis of cytopenia, particularly thrombocytopenia in patients with congenital syphilis.     

Two new cases of thrombocytopenia absent radius (TAR) syndrome: clinical, genetic and nosologic features

Two unrelated children affected by TAR syndrome, autosomic recessive disease with congenital thrombocytopenia and bilateral radial aplasia, are described. In the first case a mild thrombocytopenia has been compatible with a fairly normal life until the second year of age. The other child shows radial aplasia associated with other anomalies of the upper limbs, severe thrombocytopenia and leukemoid reaction. The relationship among TAR syndrome, Fanconi's anemia and Roberts' syndrome are briefly discussed.     

CHRONIC PULMONARY DISEASE IN A CHILD WITH THE EHLERS-DANLOS SYNDROME

ABSTRACT. The presence of chronic pulmonary disease is an uncommon finding in the Ehlers-Danlos syndrome. The patient discussed herein presented with severe irreversible obstructive pulmonary disease characterized by marked hyperinflation, an increase in static lung compliance, and tracheal dilatation. A largely normal lung biopsy ruled out chronic pulmonary emphysema. Despite the similarity of this patient to those with the Mounier-Kuhn syndrome, the degree of tracheobronchial enlargement was not as great as is usually seen in this disorder although these anatomic changes may develop with time. The findings in this case demonstrate that any site within the tracheobronchial tree may be involved in the Ehlers-Danlos syndrome and further emphasize the need to determine the degree of reversibility of obstructive lung disease in children.     

CHRONIC PULMONARY DISEASE IN A CHILD WITH THE EHLERS-DANLOS SYNDROME

Abstract. The presence of chronic pulmonary disease is an uncommon finding in the Ehlers-Danlos syndrome. The patient discussed herein presented with severe irreversible obstructive pulmonary disease characterized by marked hyperinflation, an increase in static lung compliance, and tracheal dilatation. A largely normal lung biopsy ruled out chronic pulmonary emphysema. Despite the similarity of this patient to those with the Mounier-Kuhn syndrome, the degree of tracheobronchial enlargement was not as great as is usually seen in this disorder although these anatomic changes may develop with time. The findings in this case demonstrate that any site within the tracheobronchial tree may be involved in the Ehlers-Danlos syndrome and further emphasize the need to determine the degree of reversibility of obstructive lung disease in children.     

Ehlers-Danlos Syndrome Type VI (EDS VI): problems of diagnosis and management

Ehlers-Danlos Syndrome Type VI (EDS VI) is a rare autosomal recessively inherited connective tissue disorder, which poses several problems of diagnosis and management. We report on a patient who developed severe kyphoscoliosis long before the diagnosis was reached. We conclude that early biochemical diagnosis and a timely operative procedure by extensive posterior instrumentation is the basis for successful management of this disorder.     

Heritable disorders of connective tissue: Ehlers-Danlos syndrome.

The Ehlers-Danlos syndrome is a relatively common heritable disorder of connective tissue. The cardinal features are cutaneous hyperextensibility, joint hypermobility, bleeding diathesis, and tissue fragility, and these features lead to a large variety of additional manifestations. Of the eight presently described types, four varieties have been found to be caused by defects in the biogenesis of collagen, the major structural protein of the body. Consideration of the clinical features and probable mode of inheritance will permit subclassification of many patients into specific types, and biochemical confirmation is possible for several varieties.     

Raynaud syndrome in childhood

Twenty-seven patients with Raynaud syndrome (mean age at onset 11.7 years) were studied to determine the prevalence of primary Raynaud syndrome and to assess the predictive role of antinuclear antibody, nail-fold capillary microscopy, and photoelectric plethysmography in this population. Fourteen patients (52%) had a connective tissue disease, four (15%) had a probable connective tissue disease, and nine (33%) had primary Raynaud syndrome. In all patients with either a connective tissue disease or a probable connective tissue disease, there was a positive reaction to antinuclear antibody, in contrast to patients with primary Raynaud syndrome, in whom antinuclear antibody was not detected. Nail-fold capillary microscopy scores differed significantly between patients with either a connective tissue disease or a probable connective tissue disease and those with primary Raynaud syndrome for both enlarged loop score (p less than 0.025 and less than 0.05, respectively) and avascular score (p less than 0.005 and less than 0.01, respectively). Photoelectric plethysmography scores were reduced in all groups but did not differ significantly between groups. Our findings suggest that in children with Raynaud syndrome, the primary type is more common than was originally suspected, and that both antinuclear antibody and nail-fold capillary microscopy, but not photoelectric plethysmography, can distinguish patients with primary Raynaud syndrome from those with either a connective tissue disease or a probable connective tissue disease.