Spondylothoracic dysostosis: report of two cases and review of the literature.

Two Puerto Rican infants, offsprings of nonconsanguineous parents, died with spondylothoracic dysostosis as characterized by widespread anomalies of the spine (malformed vertebral bodies including hemivertebrae), deformity of the thorax, and fan-like configuration of the ribs. The disease was lethal in early life in the 18 cases previously reported. An autosomal-recessive inheritance has been described. Spondylocostal dysostosis, a related entity, showed associated intrinsic anomalies of the ribs. The 17 cases culled from the literature pursued a milder course, affected mainly older children and adults, and had a different pattern of inheritance.     

Human metapneumovirus associated with respiratory tract infections in a 3-year study of nasal swabs from infants in Italy

The newly described human metapneumovirus (hMPV) is reported here to be more commonly associated with lower respiratory tract disease. The present study examined nasal swab specimens from 90 infants with acute respiratory tract infections in Pisa, Italy, over a period of three respiratory virus seasons. The incidence of infection varied in each of the 3 years, with the rates of positivity for hMPV being 7% in 2001 but 37 and 43% in 2000 and 2002, respectively. hMPV was noted to occur seasonally in a pattern typical of the frequency of occurrence of respiratory syncytial virus. More than one-half (14 of 23) of the infants infected with hMPV had bronchopneumonia. One-third (9 of 23) of the hMPV-infected patients were also infected with another respiratory virus, a relationship that has not previously been reported. Mixed infections did not account for a higher percentage of cases of bronchopneumonia than hMPV infection alone did. Furthermore, 7 of 17 infants whose plasma was also tested for hMPV RNA were demonstrated to have virus in both nasal swab and blood specimens. The study indicates that hMPV is seen as commonly as other respiratory viruses, may be associated with severe respiratory disease in infants, can establish mixed infections with other respiratory viruses, and has a seasonal occurrence.     

Sib pair with previously unreported skeletal dysplasia

We report on a consanguineous Lebanese family in which a sister and brother had developmental delay, dysmorphic facial appearance, narrow chest, prominent abdomen, and short limbs. Neonatal radiographs disclosed a bell-shaped thorax, short ribs, some with a cupped end, severe platyspondyly, square iliac bones, horizontal acetabula with medial and lateral spurs, hypoplastic ischia, short long bones, slight widening of the distal femoral metaphyses, and absence of epiphyseal ossification of the knees. The girl died at age 9 months as a result of respiratory insufficiency. A clinical and radiological follow-up of the boy showed that the axial hypotonia, minor anomalies, and short stature were still present, whereas the bone abnormalities had improved. Differential diagnosis suggests that this is a new type of chondrodysplasia.     

A case of campomelic dysplasia without sex reversal

Campomelic dysplasia (CD; OMIM #114290), a rare form of congenital short-limbed dwarfism, is due to mutations in SOX9, a member of the SOX (SRY-related HMG box) gene family. Multiparous mother at 38 weeks' gestation delivered a 3,272 g baby boy with characteristic phenotypes including bowing of the lower limbs, a narrow thoracic cage, 11 pairs of ribs, hypoplastic scapulae, macrocephaly, flattened supraorbital ridges and nasal bridge, cleft palate, and micrognathia. He underwent a tracheostomy at the age of three months for severe laryngomalacia after a number of repeated hospitalizations due to respiratory problems and died at the age of four months from progressive respiratory failure. He was diagnosed as having CD based on a novel frameshift mutation (p.Gln458ArgfsX12) in the SOX9 gene, the mutation which has not yet been reported in Korea.     

Chronic respiratory disease in premature infants caused by Chlamydia trachomatis.

The relation between chronic respiratory disease and infection with Chlamydia trachomatis in premature infants was investigated to ascertain the aetiological importance of intrauterine C trachomatis infection and chronic respiratory disease in premature infants. Serum IgM antibodies against C trachomatis were determined by enzyme linked fluorescence assay. Sections of lung tissues obtained by biopsy and at necropsy were also tested for the presence of antigens using fluorescein conjugated monoclonal antibodies to C trachomatis. Of 16 sera from premature infants with chronic respiratory diseases clinically diagnosed as bronchopulmonary dysplasia or the Wilson-Mikity syndrome, five had IgM antibodies to C trachomatis L2 strain by enzyme linked fluorescence assay (titre greater than or equal to 1/500). Of 37 sera from premature infants with extremely low birth weights, two had IgM antibodies to C trachomatis. No specific IgM antibody was detected in 31 neonates who showed raised serum IgM concentrations but who did not have respiratory tract symptoms. C trachomatis was identified from two specimens of lung tissue obtained at necropsy from premature infants with chronic respiratory disease positive for IgM antibody. These findings indicate the aetiological importance of intrauterine C trachomatis infection in chronic respiratory disease in premature infants.     

A new short rib syndrome: Report of two cases

We describe two unrelated malformed infants who died shortly after birth and who had multiple congenital anomalies including hydrops and ascites, facial abnormalities (with median cleft of the upper lip), narrow thorax, protuberant abdomen, and short, bowed limbs. Postmortem radiographs showed very short ribs and disproportionately short long tubular bones; no metaphyseal abnormalities were present. Comparison with earlier described short-rib/short-rib-polydactyly syndromes suggest that the disorder present in our two cases is a new type of short-rib syndrome. One of our patients was born to a consanguineous couple; in a subsequent pregnancy, real-time ultrasonography in the second trimester showed that the female fetus had the same abnormalities as its sib. Diagnosis was confirmed after elective abortion. This suggests that this short-rib syndrome may be an autosomal recessive disorder.     

Prevention of asthma with ketotifen in preasthmatic children: a three-year follow-up study

Growing morbidity and mortality rates call for research towards more effective methods of preventing asthma. During the last decade several groups have reported the results of natural history and asthma prevention studies. However, the attempt to prevent development of asthma in genetically predisposed children, has not resulted in a generally accepted management scheme. The aim of this study was to evaluate the effectiveness of ketotifen in preventing the onset of asthma in infants considered to be at high risk of developing the disease, but who had no history of respiratory obstruction. These children have been described as preasthmatic. In this double-blind, placebo-controlled, parallel study, 100 infants with a family history of major allergy and elevated serum IgE levels, but with no history of bronchial obstruction, were treated with either ketotifen (n= 50) or placebo (n= 50) over a 3-year period. There were no statistically significant differences between the two groups with regard to age, sex, degree of hereditary allergy, levels of serum IgE upon joining the study, and family smoking habits. At the end of 3 years, only four of the 45 infants who had received ketotifen had developed asthma (9%). Of the 40 children given placebo, 14 had developed asthma (35%) (P= 0.003). These results suggest that ketotifen is effective in preventing the onset of asthma in preasthmatic children.     

Human Bocavirus: Passenger or Pathogen in Acute Respiratory Tract Infections?

Human bocavirus (HBoV) is a newly identified virus tentatively assigned to the family Parvoviridae, subfamily Parvovirinae, genus Bocavirus. HBoV was first described in 2005 and has since been detected in respiratory tract secretions worldwide. Herein we review the literature on HBoV and discuss the biology and potential clinical impact of this virus. Most studies have been PCR based and performed on patients with acute respiratory symptoms, from whom HBoV was detected in 2 to 19% of the samples. HBoV-positive samples have been derived mainly from infants and young children. HBoV DNA has also been detected in the blood of patients with respiratory tract infection and in fecal samples of patients with diarrhea with or without concomitant respiratory symptoms. A characteristic feature of HBoV studies is the high frequency of coinciding detections, or codetections, with other viruses. Available data nevertheless indicate a statistical association between HBoV and acute respiratory tract disease. We present a model incorporating these somewhat contradictory findings and suggest that primary HBoV infection causes respiratory tract symptoms which can be followed by prolonged low-level virus shedding in the respiratory tract. Detection of the virus in this phase will be facilitated by other infections, either simply via increased sample cell count or via reactivation of HBoV, leading to an increased detection frequency of HBoV during other virus infections. We conclude that the majority of available HBoV studies are limited by the sole use of PCR diagnostics on respiratory tract secretions, addressing virus prevalence but not disease association. The ability to detect primary infection through the development of improved diagnostic methods will be of great importance for future studies seeking to assign a role for HBoV in causing respiratory illnesses.     

Diaphanospondylodysostosis (DSD): confirmation of a recessive disorder with abnormal vertebral ossification and nephroblastomatosis

We report on four patients from three families, with similar radiological findings: absent (or severely delayed) ossification of vertebral bodies and associated anomalies. The babies were stillborn or died soon after birth of respiratory insufficiency. Two patients are sibs (female and male) born to first cousin Malian parents. The two others were non-consanguineous. This perinatally lethal entity comprises short neck, short wide thorax, and normally shaped limbs. Associated, inconstant anomalies are myelomeningocele, cystic kidneys with nephrogenic rests (in the sibs), and cleft palate. Radiologically, the hallmarks are absence of ossification of the vertebral bodies and sacrum, abnormal position of the vertebral pedicles, which are lamellar and angulated, ribbon-like ribs reduced in number, narrow pelvis, upward widening of the iliac wings, and unusual tilt of the ischiopubic rami, contrasting with the normal appendicular skeleton. Maroteaux briefly described one of the patients in the 2002 edition of "Maladies osseuses de l'enfant" and three sibs with similar renal and radiological findings were reported in 2003 in this Journal. Combined with the latter cases, these four new patients allow delineation of a specific lethal AR syndrome with ossification defect of the axial skeleton and renal dysplasia. We propose to name this entity diaphanospondylodysostosis.     

Cerebro-costo-mandibular syndrome

We describe two boys with cerebro-costo-mandibular syndrome (CCMS). Both patients presented with Pierre Robin anomaly respiratory insufficiency died 12 hours and 10 months after birth. The first boy had muscular hypotonia, severe micrognathia, glossoptosis, short palate, preauricular tag, paraumbilical fibroma, and a small and narrow thorax. His chest roentgenographs showed marked hypoplasia of the first to tenth rib, multiple posterior rib-gaps in the only four ossified ribs. Tracheomalacia and stenosis of the left ureter was observed during autopsy. No structural cerebral anomalies were observed. Respiratory distress necessitated a tracheostomy in the second boy. He had severe micrognathia with glossoptosis and a cleft soft palate were noted. His chest roentgenograph showed a bell-shaped, small thorax with multiple dorsal rib-gap defects. CCMS is a rare disorder often associated with Pierre Robin anomaly. Chest roentgenographs show the typical posterior rib-gap defects, which are quite variable. CCMS usually occurs as an isolated event in a family. Of 41 reported families four reports describe horizontal and two describe vertical transmission of CCMS. This might imply genetic heterogeneity with autosomal recessive and autosomal dominant inheritance. Inter- and intrafamilial expression is variable. Careful family studies are necessary before genetic counseling is given. © 1996 Wiley-Liss, Inc.     

Endotoxin exposure, wheezing, and rash in infancy in a New Zealand birth cohort

BACKGROUND: Wheezing in infancy is common and is associated with small lungs, viral respiratory tract infection, and environmental tobacco smoke exposure. Recently, increased levels of endotoxin in the domestic environment have also been associated with infant wheezing, particularly among infants with a family history of atopic disease. OBJECTIVE: To explore associations between exposure to endotoxin at 3 months of age and reported symptoms of wheezing, rhinitis, itchy scaly rash, and atopy at 15 months in a birth cohort of 881 New Zealand children. METHODS: Using standardized methods, a 1-m(2) site from the bedroom floors of the 3-month-old infants was sampled and analyzed for endotoxin. RESULTS: Wheezing was significantly associated with higher endotoxin levels (odds ratio [OR], 1.54; 95% CI, 1.03-2.30), particularly among infants with a parental history of allergic disease (OR, 1.67; 95% CI, 1.07-2.60). Higher endotoxin concentrations were also strongly associated with recurrent itchy rashes (OR, 1.87; 95% CI, 1.14-3.05), particularly among infants who were atopic (OR, 4.64; 95% CI, 1.56-13.77) or had a parental history of allergic disease (OR, 2.10; 95% CI, 1.22-3.61). CONCLUSION: Domestic endotoxin was associated with reported airway and skin symptoms in this large group of New Zealand infants. The role of endotoxin in the development of respiratory and skin disease in infancy deserves further study. CLINICAL IMPLICATIONS: Reducing domestic endotoxin exposure might reduce infant wheezing and atopic dermatitis, but the long-term benefits of this remain unclear.     

Sarcoidosis: Multiple Chest Manifestations

The multiple roentgenographic appearances of pulmonary sarcoidosis, a well-known systemic granulomatous disease of undetermined etiology, are presented. The findings in the chests of 350 patients with diagnosis of Boeck sarcoid confirms the usual and unusual manifestations which have been described in the past.^1,2     

Sclerosteosis: report of a case in a black African man

Sclerosteosis is a rare genetic disorder of bone modelling, similar to, but distinct from, van Buchem disease; it has been described almost exclusively in Afrikaners of South Africa, a white population of Dutch ancestry. Isolated cases have been reported in a girl in Japan, a boy in Spain, and in multiracial families in Brazil and USA.
Here we report a case of sclerosteosis in a black man born in Senegal. He presented with the full features of the disease: tall stature; syndactyly; nail dysplasia; massive sclerosis of the long tubular bones, the ribs, the pelvis and the skull; multiple cranial nerve involvement: optic atrophy, facial palsy and trigeminal neuralgia. Radiologic examination, visual and brainstem auditory evoked potentials, computerized tomography and magnetic resonance imaging of the skull were performed. This seems to be the first case of the disease in a black African individual, with no known relationship with Dutch ancestry.     

Antibody response and avidity of respiratory syncytial virus-specific total IgG, IgG1, and IgG3 in young children

Respiratory syncytial virus (RSV) is a major cause of acute respiratory disease in infants and young children. Considering that several aspects of the humoral immune response to RSV infection remain unclear, this study aimed to investigate the occurrence, levels, and avidity of total IgG, IgG1, and IgG3 antibodies against RSV in serum samples from children ≤5 years old. In addition, a possible association between antibody avidity and severity of illness was examined. The occurrence and levels of RSV-specific IgG depended on age, with infants <3 months old displaying high levels of antibodies, which were probably acquired from the mother. Children ≥24 months old also showed frequent occurrence and high levels of IgG, which was produced actively during infection. In addition, the avidity assay showed that the avidity of RSV-specific total IgG and IgG1 was lower in infants <3 months old who had acute respiratory disease than in age-matched controls. The avidity of RSV-specific IgG detected in children ≥24 months old with lower respiratory infection was lower than that in children with upper respiratory infection. These results indicate that the presence of high avidity RSV-specific IgG antibodies may lead to better protection against RSV infection in children <3 months old, who may have a lower probability of developing disease of increased severity. In addition, children ≥24 months old with RSV-specific IgG antibodies of low avidity tended to develop more severe RSV illness. These findings may be helpful in establishing vaccination schedules when a vaccine becomes available.     

Short-rib polydactyly syndrome,Beemer-Langer type,with bilateral huge polycystic renal dysplasia: an autopsy case.

Short rib-polydactyly syndrome (SRPS) is a group of lethal skeletal dysplasia of an autosomal recessive inheritance characterized by markedly narrow ribs, micromelia, and multiple anomalies of major organs. We report a case of type IV SRPS with uncommon associations of polydactyly and bilateral polycystic kidneys, in a 28 week old female fetus. She was born dead to a 28 year old mother, showing a hydropic change, narrow thorax, and shortened limbs with postaxial heptasyndactyly of both hands and feet. Radiologic examination revealed short horizontal ribs, curved short tubular limb bones, small ilia and scapula, and a mild vertebral abnormality. Postmortem examination disclosed pulmonary hypoplasia, pancreatic cysts, hepatic fibrosis, and left persistent superior vena cava. In addition this case had bilateral huge polycystic renal dysplasia that was seldom described in any type of SRPS. Histologic sections of the vertebrae disclosed abnormal enchondral ossification with irregular and retarded hypertrophic zone.     

Probiotics in prevention of IgE-associated eczema: a double-blind, randomized, placebo-controlled trial

BACKGROUND: An altered microbial exposure may underlie the increase of allergic diseases in affluent societies. Probiotics may alleviate and even prevent eczema in infants. OBJECTIVE: To prevent eczema and sensitization in infants with a family history of allergic disease by oral supplementation with the probiotic Lactobacillus reuteri. METHODS: Double-blind, randomized, placebo-controlled trial, which comprised 232 families with allergic disease, of whom 188 completed the study. The mothers received L reuteri ATCC 55730 (1 x 10(8) colony forming units) daily from gestational week 36 until delivery. Their babies then continued with the same product from birth until 12 months of age and were followed up for another year. Primary outcome was allergic disease, with or without positive skin prick test or circulating IgE to food allergens. RESULTS: The cumulative incidence of eczema was similar, 36% in the treated versus 34% in the placebo group. The L reuteri group had less IgE-associated eczema during the second year, 8% versus 20% (P = .02), however. Skin prick test reactivity was also less common in the treated than in the placebo group, significantly so for infants with mothers with allergies, 14% versus 31% (P = .02). Wheeze and other potentially allergic diseases were not affected. CONCLUSION: Although a preventive effect of probiotics on infant eczema was not confirmed, the treated infants had less IgE-associated eczema at 2 years of age and therefore possibly run a reduced risk to develop later respiratory allergic disease. CLINICAL IMPLICATION: Probiotics may reduce the incidence of IgE-associated eczema in infancy.     

Partial trisomy 3p syndrome

Two cousins with an unbalanced chromosome translocation (partial trisomy 3p) are described. Both children have a clinically recognizable syndrome of square facies with prominent cheeks, narrow bitemporal regions, psychomotor retardation and congenital heart disease. Extended family studies showed one other individual proven to have partial trisomy 3p karyotype, two retarded individuals with congenital heart disease who probably had it, and 14 balanced carriers of the translocation t(1;3)(q43;p21). This report confirms the characteristic clinical appearance of affected individuals and emphasizes the frequency in which congenital heart disease is the presenting feature of partial trisomy 3p. An additional 22 cases of partial 3p trisomy are reviewed.     

Familial cutaneous amyloidosis with systemic manifestations in males

We describe a family in which two males and seven females have brown pigmentation of the skin. In the females, the type and distribution of the pigmentation mimicked incontinentia pigmenti; in the males, the pattern was reticulate. The histological appearance was the same in both sexes with amyloid deposits in the papillary dermis, melanin in the basal layer, and slight hyperkeratosis. The females were otherwise normal. Both males had thrived poorly as infants but had survived. One had severe gastroenteritis with blood in the stools starting at the age of three weeks followed by seizures, hemiplegia, and developmental delay; the other had recurrent pneumonia throughout life, a urethral stricture, inguinal herniae, and near-blindness from amyloid deposition in the cornea. Five other males in the family had had severe illnesses. Two died of pneumonia by three months. One died at three months from colitis. Both remaining boys had colitis as infants, failed to thrive, and developed recurrent pneumonia from which one died at three years. We think all of these relatives had the same disease carried by a single gene with pleiotropic effects. The most likely form of inheritance is X-linked.     

Severe respiratory distress due to ileal duplication cyst in the newborn

Differential diagnosis of neonatal respiratory distress includes pulmonary and systemic disorders and anatomic problems compromising respiratory system. We report on a 2770-g female born to a 29-year-old gravida 3, para 2 woman after 34 weeks of gestation. Antenatal ultrasound performed in week 8 and 21 was normal. The infant was delivered by cesarean section after amniotic membranes had been ruptured for less than 12 hours due to signs of fetal distress. The Apgar score was 3 and 3 at 1 and 5 minutes, respectively. The infant was intubated and resuscitated, and transferred immediately to the neonatal intensive care unit. She had an extremely protuberant and cyanotic abdomen. Dilated cutaneous collateral vessels were apparent in the periumbilical region. Abdominal sonography showed cystic multiloculated tumorous mass filled with dense, flocculent content at the level of hepatic portal. The tumorous mass occupied the majority of the abdomen with caudal extension toward the pelvis and dorsally toward the spine. The liver was displaced high under the diaphragm with the left liver lobe in the left hemiabdomen. On x-ray the lung were collapsed due to a large abdominal mass in the right hemiabdomen that displaced the right diaphragm and intestines contralaterally. She soon developed bilateral pneumothoraces. Drainage and continuous suction were started. The infant failed to improve despite all attempts and died. On autopsy, an extremely large, mobile, multichambered, solitary cyst was found. It was attached to the mesenteric side of the ileum by its own thin peduncular stalk and had no communication with the remainder of the gut. It occupied the majority of the abdomen. Histologic section revealed a well-developed smooth muscle wall and inner mucosa of small bowel type. Respiratory distress is a common problem in premature infants. The majority of cases are due to pulmonary disorders (e. g., hyaline membrane disease, meconium aspiration syndrome, pneumonia), hypothermia, metabolic acidosis, anemia, and congenital heart disease. Anatomic problems including space occupying lesions are less common. Duplications of the alimentary tract in infants and children are rare congenital anomalies. Although symptoms can occur at any age, they usually present during the first year. In our patient, intraabdominal mass caused severe respiratory distress and respiratory failure in the first hours of postnatal life. This had been seen before only as a complication of intrathoracic lesions extending into the abdominal cavity. Pathology revealed spherical intestinal duplication that was completely separated from the alimentary tract. Embryologically, it was a localized duplication. Respiratory distress in our patient was refractory to all means of mechanical ventilation. Poor lung compliance was the consequence of prenatal lung hypoplasia and inadequate postnatal lung expansion due to the duplication cyst space occupying character and its compressive effect. Prenatal diagnosis was the child's only chance for survival but it was not made. Duplications of the alimentary tract can present a diagnostic challenge even in the first hours of life. They should be included in the differential diagnosis of severe respiratory distress, especially in premature infants in which timely prenatal diagnosis cannot be always made. We propose their inclusion among other space occupying lesions that might be the cause of severe respiratory distress even in the earliest neonatal period.