Further delineation of the 22q13 deletion syndrome.

A chromosomal deletion syndrome associated with a 22q13 microdeletion has previously been reported in approximately 75 children. We report six cases from Denmark with a deletion of 22q13. One was cytogenetically visible by conventional karyotyping, one was diagnosed by high resolution karyotyping after the demonstration of low arylsulfatase A activity. Two were diagnosed by high resolution CGH analysis, one was diagnosed by multisubtelomeric FISH analysis and one was diagnosed serendipitously as lack of the control signal in a FISH analysis for 22q11 deletion. One of the cases was a mosaic with 16% of cells showing two signals. The phenotype of the children included: generalized developmental delay, compromised language development, hypotonia, normal or accelerated growth and minor facial dysmorphism. Other features were partial agenesis of the corpus callosum, bilateral ureteropelvic stricture, gastroesophageal reflux and hearing loss. One case had a different phenotype, and showed a deletion as well as a duplication. The extent of the deletion was studied by quantitative PCR analysis of a number of DNA markers in the 22q13 region. The deletions varied in size, extending from 4.0 to 9.0 Mb. The clinical phenotype seemed rather similar although some specific features might be attributable to differences in deletions.

Perinatal risk factors of adverse outcome in very preterm children: a role of initial treatment of respiratory insufficiency?

AIM: To investigate risk factors of adverse outcome in a cohort of very preterm children treated mainly with nasal continuous positive airway pressure (CPAP) during the neonatal course. METHODS: In Denmark, preterm children are treated with nasal CPAP as a first approach to respiratory support. A national prospective study of all infants with a birthweight below 1000 g or a gestational age below 28 wk born in 1994-1995 was initiated to evaluate this approach. Of the 269 surviving children 164 (61%) were not treated with mechanical ventilation in the neonatal period. A follow-up of the children at 5 y of age was conducted. Data from the neonatal period and the 5-y follow-up were analysed. RESULTS: In multivariate analyses including 250 children, a severely abnormal neonatal brain ultrasound scan was predictive of cerebral palsy (OR = 19.9, CI 95%: 6.1-64.8) and intellectual disability (OR = 6.2, CI 95%: 2.3-16.5). A high Clinical Risk Index for Babies (CRIB) score (OR = 2.4, CI 95%: 1.1-5.5) and chronic lung disease (OR = 2.8, CI 95%: 1.2-6.9) were predictive of intellectual disability. In univariate analyses mechanical ventilation was associated with cerebral palsy (OR=4.3, CI 95%: 1.7-10.8) and intellectual disability (OR = 2.2, CI 95%: 1.2-4.2), but the associations became insignificant in multivariate analyses including chronic lung disease and a severely abnormal ultrasound scan. CONCLUSION: The associations between neonatal risk factors and adverse outcome in our cohort were very similar to those found in other cohorts with another initial treatment of respiratory insufficiency. We found no significant adverse effects of mechanical ventilation beyond what could be explained by associations with chronic lung disease and IVH 3-4/PVL.

[Severe neonatal hyperparathyroidism in a family with familial hypocalciuric hypercalcemia]. / Neonatal svaer hyperparatyreoidisme i en familie med familiaer hypokalciurisk hyperkalcaemi.

Familial hypocalciuric hypocalcaemia (FHH) is a rare disorder, inherited in an autosomal dominant manner. It has earlier been believed that neonatal severe hyperparathyroidism (NSHPT) is the homozygous form of FHH, but in this case story we show that it is not always like that. We describe a girl who presents with a calcium metabolic disorder from birth. Genetic examination of the girl and her family shows a single abnormal allele in the calcium ion sensitive receptor. We discuss why some heterozygotic inactivating calcium receptor mutations cause NSHPT, while the majority of other mutations only cause mild, asymptomatic hypercalcaemia as in FHH.

Familial hypocalciuric hypercalcemia and neonatal severe hyperparathyroidism associated with mutations in the human Ca2+-sensing receptor gene in three Danish families.

We screened three unrelated Danish families with familial hypocalciuric hypercalcemia (FHH) for mutations in the Ca2+-sensing receptor (CASR) gene by polymerase chain reaction amplification and DNA sequencing of exons 2-7, which include the entire coding region of the gene. In one family the affected individuals have a T-->C mutation that changes the normal arginine at codon 220 to a tryptophan. In the other two FHH families, affected individuals have the same A-->G mutation, leading to conversion of the normal glycine at codon 552 to an arginine. These results confirm that FHH can be caused by non-conservative missense mutations in the CASR gene leading to abnormal calcium homeostasis. Both mutations are located in the amino-terminal extracellular domain of the receptor, which contains the binding site for extracellular Ca2+, the CASR's principal physiological agonist.

Effect of folic acid supplementation on small-for-gestational-age infants born at term.

The effect of 250 micrograms folic acid (FA)/day or placebo given to 21 small-for-gestational-age infants born at term was studied during the first 3 months of life. The design of the study was double blind with random allocation. No randomization was performed in respect of breast-feeding or formula-feeding with a folate content of 60-70 micrograms/l. No significant differences were observed in haemoglobin concentration, haematocrit, weight and length between FA-supplemented and non-supplemented infants. A negative correlation was demonstrated between gestational age and erythrocyte folate (E-folate) concentration at 1 week. E-folate content was higher when no supplement was given in breast-fed than in formula-fed infants.

Unusual segregation in a family with a 11/21 translocation.

A familial 11/21 translocation is described where the proband has an unbalanced translocation and the oldest translocation carrier shows mosaicism with a partial trisomy no. 21.

Prostaglandin E1 treatment in ductus dependent congenital cardiac malformation. A review of the treatment of 34 neonates.

Thirty-four sick neonates with major duct dependent cardiac defects were given short term (1 h-408 h) intravenous infusions of prostaglandin E1 (alprostadil) in doses varying between 0.1 micrograms/kg/min (starting dose) and 0.01 micrograms/kg/min. The aim of the study was to establish an effective and safe regiment that could be initiated after clinical diagnosis of a severe duct dependent cardiac defect, whose clinical course would be adversely affected by ductus closure. After an initial dosage of 0.1 micrograms/kg/min, effective clinical improvement was achieved in 28 infants (82%). In all 28 responders, the effect was maintained at a reduced dosage of 0.05 micrograms/kg/min, and in 21 a low dosage of 0.01 micrograms/kg/min was effective. Side effects, which occurred in 21 infants (62%), were reversible and dose related, and no serious side effects were noted at a dosage of less than 0.05 micrograms/kg/min. A starting dose of 0.05 micrograms/kg/min with subsequent reduction is recommended, but in case of institution of treatment before transfer to a pediatric cardiac centre a lower starting dose of 0.01 micrograms/kg/min may be preferred.

Primary hyperparathyroidism in infancy associated with familial hypocalciuric hypercalcemia.

Clinical and biochemical evidence of primary hyperparathyroidism (prim. HPT) is reported in an infant with hypotonia, feeding problems and constipation from birth. Following a partial parathyroidectomy at the age of 12 months, the clinical condition improved. In her sister, mother and three other maternal relatives a familial hypocalciuric hypercalcemia (FHH) was subsequently demonstrated. All were clinically healthy in spite of increased total and ionized serum calcium, normal serum parathyroid hormone concentration, low urinary calcium excretion and normal renal excretion of cyclic AMP. Similar findings appeared in our patient after parathyroidectomy. An autosomal dominant inheritance of FHH is suggested. It is thus demonstrated, that a mother with FHH may give birth to healthy children with FHH as well as to infants with prim. HPT associated with FHH.

Transcutaneous PO2 monitoring during treatment with continuous positive airway pressure in infants with idiopathic respiratory distress syndrome.

During a 20-month period, 20 infants with idiopathic respiratory distress syndrome (IRDS) were treated with continuous positive airway pressure (CPAP) when they required at least 40% inspired oxygen. The infants were allocated to monitoring with either repeated blood-gas determinations according to the usual practice or continuous transcutaneous PO2 measurements supplemented by blood-gas measurements only when judged necessary. The groups were comparable with regard to birth weight and gestational age, and did not differ significantly with regard to effectiveness or duration of the CPAP treatment, survival rates (90 versus 80%) or number of complications. None developed retrolental fibroplasia. However, PtcO2 monitoring resulted in significantly less hypo- and hyperoxaemia and the number of blood-gas analyses performed during CPAP therapy amounted to only 0.6 per infant per day in the transcutaneously monitored group as against 5.3 in the other group. We propose that PtcO2 monitoring should now be the method of choice and that the use of umbilical artery catheterization should be restricted to selected groups of very low birth-weight infants and to infants in need of ventilator therapy.

Colobomata of the iris, ciliary body and choroid in an infant with oesophago-tracheal fistula and congenital heart defects. An unknown malformation complex.

A malformation pattern, not previously reported consisting of microphthalmia, uveal coloboma, oesophago-tracheal fistula and congenital heart defects is presented. The phaenotypical similarity and difference from previously reported cases are discussed.

Urinary loss of oxypurines in hypoxic premature neonates.

The daily urinary excretion of the oxypurines hypoxanthine, xanthine and uric acid during each of the first 3 days of life was determined in premature infants without hypoxia (PI) and in hypoxic premature infants (HPI) with the respiratory distress syndrome. The loss of uric aic was statistically significantly greater in the HPI during days 1, 2, and 3 of life, and so was the loss of xanthine on days 1, and 2, but not on day 3. As to the loss of hypoxanthine, no difference could be shown. In both groups of infants the excretion of hypoxanthine and xanthine together made up about 2% of the total oxypurine loss for each day, the loss of xanthine being the greater of the two. The results did not seem to bear relation to differences between the two groups concerning urinary output, birth weight, gestational age, method of delivery, or administration of exogenic purines. So it appears that the increased loss of oxypurines in HPI is caused by the impact of hypoxia, probably owing to be compromised cellular respiration with a subsequent general displacement of the purine metabolism in the catabolic direction.

Operative treatment of cerebral arteriovenous aneurysm of vein of Galen complicated by congestive heart failure.

A rare cause of congestive heart failure in the neonatal period is an intracranial arteriovenous malformation, but this condition should be borne in mind when there is unexplained right-sided congestive heart failure. A case is reported of an aneurysm of the great vein of Galen, complicated by congestive heart failure. Successful surgical treatment was carried out using a two-stage procedure.

The absence of factor II in a child with systemic lupus erythematosus.

This report describes a patient with active system lupus erythematosus (SLE), who developed haemorrhagic diathesis due to a lowering of plasma factor II activity. No evidence was found suggesting a plasma inhibitor of factor II. The present case indicates that in some patients with SLE, factor II activity may be low or completely absent due to impairment of factor II synthesis, further that prednisone, but not azathioprine, may ameliorate this defect.