A new type of leukoencephalopathy with metaphyseal chondrodysplasia maps to Xq25-q27.

BACKGROUND: The authors report a three-generation family with four male patients presenting with a novel type of X-chromosomal leukoencephalopathy associated with skeletal abnormalities. METHODS: The index patient and his brother reached their early motor milestones in due time and had normal language development. Between the ages of 2 and 3 years, first signs of spastic paraplegia were noticed. Furthermore, the patients developed tremor, ataxia, optic atrophy, and spastic tetraparesis. Both boys had broad wrists and knees without significant contractures. A maternal uncle and a granduncle had the same disease. RESULTS: Leukoencephalopathy (MRI, MRS) and metaphyseal chondrodysplasia (X-ray, MRI) were diagnosed. MRS showed a reduction of choline-containing compounds in the white matter. An autopsy on one of the patients, who died at age 37 years, revealed an orthochromatic type of leukoencephalopathy. In bone and cartilage tissue, unspecific signs of a mild chondrodysplasia were found. At the PLP gene locus an obligate recombination was observed, which excludes the Pelizaeus-Merzbacher locus on Xq21-22. However, affected males share a fragment of the long arm of chromosome X. CONCLUSION: The authors report a new type of leukoencephalopathy associated with metaphyseal chondrodysplasia located on Xq25-q27.

[High-resolution computed tomography of the lungs in pediatric patients]. / Hochauflösende Computertomographie der Lunge im Kindesalter.

Since the introduction of the high-resolution technique more than ten years ago, HRCT has become an established modality for diagnosing diseases of the respiratory system. This is especially true for the diagnosis of lung diseases in adults. Experience in HRCT of the lungs is limited in pediatric patients. This review gives an overview of frequent and less frequent HRCT findings in pulmonary diseases in childhood. A purely reticular pattern is rarely observed in infants. Pulmonary diseases associated with overinflation are relatively frequent. Paired inspiratory-expiratory scans combine morphological analysis with functional information and have improved the diagnosis of air trapping, e. g. in post-infectious bronchiolitis obliterans or bronchopulmonary dysplasia. Especially in children the high radiation exposure is a problem. Even when applying a low-dose protocol the radiation dose of HRCT will still exceed the dose of a chest X-ray by 100 times. The indication for pediatric pulmonary HRCT is limited to selected cases and it should be decided in agreement with the pediatric radiologists and the pediatric pulmonologists.

Short rib-polydactyly syndrome type III: comparison of ultrasound, radiology, and pathology findings.

Short rib-polydactyly syndrome (SRPS; types I-IV) is an autosomal recessive, lethal skeletal dysplasia characterized by short-limb dysplasia, narrow thorax, and polydactyly. This syndrome is invariable and can be detected by 2-trimester ultrasound. The underlying gene has not been discovered yet. We report a case of SRPS subtype III Verma-Naumoff-Le Marec that was sonographically detected at 20 weeks' gestation and compare prenatal ultrasound with postmortem findings from pathology and radiology. Since the risk of recurrence is 25%, early ultrasound for consecutive pregnancies was advised and performed at 11+6 weeks' gestation in the following pregnancy without any findings. Ultrasound diagnosis in this rare case of SRPS is a valuable tool for identification and early management, since there are no specific biochemical or histopathological markers for this syndrome. Radiological and pathological findings confirmed SRPS type III and assisted in the differential diagnosis of the subtype.

Randomized comparison of high-frequency ventilation with high-rate intermittent positive pressure ventilation in preterm infants with respiratory failure.

OBJECTIVE: In a randomized, controlled, multicenter trial, we tested the hypothesis that high-frequency ventilation (HFV) with a high lung volume strategy results in fewer treatment failures than intermittent positive pressure ventilation (IPPV) with high rates and low peak inspiratory pressures. STUDY DESIGN: Infants with a gestational age between >/=24 weeks and <30 weeks, requiring mechanical ventilation within 6 hours of birth, were randomly assigned to receive either IPPV or HFV until 240 hours after randomization, extubation, or meeting treatment failure criteria. Treatment failure, the primary end point, was determined when air leaks, an oxygenation index >35 to 45 (depending on gestational age), death, or chronic lung disease occurred. Chronic lung disease was defined as persistent requirement of mechanical ventilation, continuous positive airway pressure, or supplemental oxygen at a postmenstrual age of 36 weeks. Secondary end points included the incidence of intracranial hemorrhage. RESULTS: The third scheduled interim analysis led to termination of the trial after recruitment of 284 infants. Treatment failure criteria were met by 46% of infants receiving IPPV and 54% of infants receiving HFV (1-tailed primary hypothesis, P =.92; 2-tailed chi2 test, P =.15). Air leaks occurred in 31% and 42% (P =.042), CLD in 23% and 25%, and grade 3-4 intracranial hemorrhage in 13% and 14% of IPPV-treated and HFV-treated patients, respectively. The mortality rate before discharge was 10% in both groups. CONCLUSION: HFV with a high lung volume strategy did not cause less lung injury in preterm infants than IPPV with a high rate and low peak inspiratory pressures.

A further case of vertical transmission of proximal femoral focal deficiency?

We report on a newborn boy with congenital asymmetrically hypoplastic fibulae, lateral oligodactyly, and mild left ectrodactyly. The patient's grandfather had a short femoral shaft with a slightly smaller collodiaphyseal angle on the left as compared to the right side, probably a proximal focal femoral deficiency (PFFD). The upper limbs were not affected in either patient. PFFD in the grandfather and hypoplastic fibulae with lateral ray defects in the grandson raise the possibility of genetic transmission, specifically autosomal-dominant inheritance with variable penetrance and expressivity. This case gives further support to the fibular developmental field concept postulated by Lewin und Opitz [1986: Am J Med Genet (Suppl) 2:215-238].

Analysis of a terminal Xp22.3 deletion in a patient with six monogenic disorders: implications for the mapping of X linked ocular albinism.

The molecular characterisation of chromosomal aberrations in Xp22.3 has established the map position of several genes with mutations resulting in diverse phenotypes such as short stature (SS), chondrodysplasia punctata (CDPX), mental retardation (MRX), ichthyosis (XLI), and Kallmann syndrome (KAL). We describe the clinical symptoms of a patient with a complex syndrome compatible with all these conditions plus ocular albinism (OA1). He has a terminal Xp deletion of at least 10 Mb of DNA. Both the mother and sister of the patient are carriers of the deletion and show a number of traits seen in Turner's syndrome. The diagnosis of ocular albinism was confirmed in the patient and his mother, who shows iris translucency, patches and streaks of hypopigmentation in the fundus, and macromelanosomes in epidermal melanocytes. By comparative deletion mapping we can define a deletion interval, which locates the OA1 gene proximal to DXS143 and distal to DXS85, with the breakpoints providing valuable starting points for cloning strategies.

Hirsutism-skeletal dysplasia-mental retardation syndrome with abnormal face and a uric acid metabolism disorder.

We report on a German boy, born to nonconsanguineous parents, with an apparently new combination of multiple congenital anomalies including extraordinary hirsutism, marked brachycephaly, abnormal position of thumbs, pedes excavati with claw-toes, an abnormal face, and mental retardation. Additionally the boy manifests a disorder of uric acid metabolism. This sporadic case may represent a new syndrome due to a fresh autosomal or X-linked mutation, or chance-isolated case due to segregation of an autosomal recessive gene.

Decreased incidence of extra-alveolar air leakage or death prior to air leakage in high versus low rate positive pressure ventilation: results of a randomised seven-centre trial in preterm infants.

Two different ventilation techniques were compared in a seven-centre, randomised trial with 181 preterm infants up to and including 32 completed weeks gestational age, who needed mechanical ventilation because of lung disease of any type. Technique A used a constant rate (60 cycles/min), inspiratory time (IT) (0.33s) and inspiratory: expiratory ratio (I:E) (1:2). The tidal and minute volume was only changed by varying peak inspiratory pressure until weaning via continuous positive airway pressure. Technique B used a lower rate (30 cycles/min) with longer IT (1.0 s). The I:E ratio could be changed from 1:1 to 2:1 in case of hypoxaemia. Chest X-rays taken at fixed intervals were evaluated by a paediatric radiologist and a neonatologist unaware of the type of ventilation used in the patients. A reduction of at least 20% in extra-alveolar air leakage (EAL) or death prior to EAL was supposed in infants ventilated by method A. A sequential design was used to test this hypothesis. The null hypothesis was rejected (P = 0.05) when the 22nd untied pair was completed. The largest reduction in EAL (-55%) was observed in the subgroup 31-32 weeks of gestation and none in the most immature group (< 28 weeks). We conclude that in preterm infants requiring mechanical ventilation for any reason of lung insufficiency, ventilation at 60 cycles/min and short IT (0.33 s) significantly reduces EAL or prior death compared with 30 cycles/min and a longer IT of 1 s. We speculate that a further increase in rate and reduction of IT would also lower the risk of barotrauma in the most immature and susceptible infants.

Statural growth in Williams-Beuren syndrome.

The spontaneous growth of 165 patients (75 girls and 90 boys) with Williams-Beuren syndrome was analysed in a mixed longitudinal and cross-sectional manner. Mean (+/- 1 SD) length at birth was 48.2 +/- 2.6 cm in girls (n = 52) and 49.0 +/- 3.0 cm in boys (n = 65). Intrauterine growth retardation (length below -2 SD of the normal population) was present in 35% of the girls and 22% of the boys. Poor growth was noted during the first 2 years of life. Until age 9 years in girls and 11 years in boys, mean growth followed the 3rd percentile. A pubertal growth spurt with normal growth rate was seen at age 10 years in girls and 13 years in boys, i.e. 1 to 2 years earlier than normal. Menarche also occurred earlier than normal at a mean age of 11.6 +/- 1.5 years (n = 28). Mean adult height was 153.9 +/- 6.9 cm in girls (n = 17) and 168.2 +/- 6.9 cm in boys (n = 27), approximately corresponding to the 3rd percentile in both sexes and correlating with the genetic height potential (target height). The mean deficit of adult height compared to target height was 10.2 cm in girls and 9.1 cm in boys. Skeletal development progressed at an approximately normal rate in both sexes.

[Craniometaphyseal dysplasia--characteristic roentgen findings]. / Craniometaphysäre Dysplasie--Charakteristische Röntgenbefunde.

Craniometaphyseal dysplasia is a rare disorder of bone remodeling, which is characterized by hyperostosis or sclerosis of the skull combined with metaphyseal flaring of the long tubular bones. Diagnosis is only possible on the basis of the characteristic radiographic findings, these are shown in a case report of a 2 1/2 year old boy. There is no therapy of craniometaphyseal dysplasia.

[Cystic space occupying lesion of the upper pole of the kidney in a newborn infant. Case report and differential diagnosis]. / Zystische Raumforderung am oberen Nierenpol eines Neugeborenen. Fallbericht und Differentialdiagnose.

In a newborn female infant a cystic lesion in the upper pole of the right kidney was detected by sonography 4 weeks before an uneventful delivery. In the postnatal period the sonographic examination, IVP, CT, and the biochemical data as well were not able to classify definitely this lesion as a benign cyst, adrenal hemorrhage or cystic malignoma. Therefore a laparatomy was performed, which revealed a cystic neuroblastoma.

Pulmonary alveolar lipoproteinosis in a seven-year-old girl. A follow-up over six years.

Alveolar lipoproteinosis is a rare disease in childhood, and its outcome is considered unfavourable compared to adults. We report on the spontaneous improvement of the disease over a six-year period in a child now 13 years of age. At the time of diagnosis the vital capacity was reduced to 65% of the mean predicted for her height, but deteriorated to 40% during the following year. A bronchoalveolar lavage was performed with small amounts of fluid but it did not immediately reverse the pulmonary alterations. Contrary to expectation, in the following years there was a continuous and gradual increase of the vital capacity to 70% of the mean predicted without specific therapy. This observation underlines the importance of an individual approach to prognosis in this disease and contributes to discussion of therapeutic procedures in the paediatric age group.

Densitometric measurement of renal echogenicity in infants and naked eye evaluation: a comparison.

The sonograms of 115 infants with normal renal function ranging in age from 1 to 120 days used to determine renal parenchymal echogenicity by densitometry. The measured values were contrasted with the evaluations of 4 independent examiners who rated renal echogenicity as "less than", "equal to" or "greater than" that of the liver. The results revealed that naked eye evaluation does not permit a clear distinction between the categories of echogenicity and also that the assessments of the individual examiners differed considerably. Contrary to the previously held view the present findings indicate that the initially increased renal parenchymal echogenicity in neonates has developed into the normal hypoechoic condition after 1 month. One should take these findings into account when evaluating renal sonograms of infants, especially if no densitometric data are available.

[Lipoma of the corpus callosum in an infant with seizures]. / Balkenlipom bei einem Säugling mit Krampfanfällen.

A 3 month-old boy was admitted because of short convulsions commencing with a peculiar grin. A lipoma of the corpus callosum was diagnosed by X-ray of the skull, cranial ultrasound, CT and magnetic resonance tomography. Following treatment with phenobarbital convulsions were not observed any longer. Surgical removal of the tumour was not indicated.

[Mediastinal teratoma in a newborn infant]. / Mediastinalteratom bei einem Neugeborenen.

A newborn with mediastinal teratoma developed tachypnea and cyanosis within the first hours of life. Chest x-ray revealed a subtotal opacification of the left hemithorax, which at first was suspected to be caused by a cardiomegaly. Ultrasound examination demonstrated a large mass in the left hemithorax with multiple echo-free areas. This finding was suspicious for a mediastinal teratoma. The tumor which was originating from the mediastinum was apple-sized and could be resected totally by thoracotomy. Histology revealed a cystic teratoma covered with normal thymus tissue.