A novel mutation in PYCR1 causes an autosomal recessive cutis laxa with premature aging features in a family.

The autosomal recessive form of type II cutis laxa (ARCL II) is characterized by the appearance of redundant, inelastic skin with wrinkling, an aged look and additional variable systemic involvement including intrauterine growth retardation, failure to thrive, developmental delay, dysmorphism, osseous abnormality, and CNS manifestations. Several genetic defects have been found in patients and families with the clinical manifestations of ARCL II. Recently, mutations in PYCR1 have been linked to cutis laxa with progeroid features. We ascertained two siblings with of ARCL II born to non-consanguineous parents. Mutation analysis of PYCR1 revealed a novel single-base deletion (c.345delC) in exon 4 leading to frame-shift and premature stop of translation. The effect of this mutation results in a strong reduction of PYCR1 expression in skin fibroblasts from affected siblings. These two cases extend the genotypic spectrum of PYCR1-related ARCL II.

Compound heterozygous mutations in PYCR1 further expand the phenotypic spectrum of De Barsy syndrome.

De Barsy syndrome (DBS) is characterized by progeroid features, ophthalmological abnormalities, intrauterine growth retardation, and cutis laxa. Recently, PYCR1 mutations were identified in cutis laxa with progeroid features. Herein, we report on a DBS patient born to a nonconsanguineous Chinese family. The exceptional observation of congenital glaucoma, aortic root dilatation, and idiopathic hypertrophic pyloric stenosis in this patient widened the range of symptoms that have been noted in DBS. Mutation analysis of PYCR1 revealed compound heterozygous PYCR1 mutations, including a p.P115fsX7 null mutation allele and a second allele with two missense mutations in cis: p.G248E and p.G297R. The effect of mutation results in a reduction of PYCR1 mRNA expression and PYCR1 protein expression in skin fibroblasts from the patient. The findings presented here suggest a mutation screening of PYCR1 and cardiovascular survey in patients with DBS.

Neurodevelopment in very low birth weight premature infants with postnatal subependymal cysts.

The aim of this study was to investigate the neurodevelopmental outcome in very low birth weight infants with postnatal subependymal cysts. During a 3-year period, postnatal subependymal cysts were diagnosed by serial cranial ultrasound in 21 very low birth weight infants born prior to 33 weeks' gestation. These infants and 116 healthy very low birth weight controls were evaluated with the Bayley Scales of Infant Development at 2 years of age. Preterm infants with postnatal subependymal cysts had a significantly lower Psychomotor Development Index (P = .034) and were more likely than the normal group to have motor developmental delay (Psychomotor Development Index <70) (P = .013). The findings indicate that postnatal subependymal cyst is a significant risk factor for impaired motor development in very low birth weight infants (odds ratio 5.73, 95% confidence interval 1.57-20.97).

Outcome of Preterm Infants With Postnatal Cytomegalovirus Infection via Breast Milk: A Two-Year Prospective Follow-Up Study.

Approximately 15% of preterm infants may develop postnatal cytomegalovirus (CMV) infection from seropositive mothers via breast milk and are at risk for neurological sequelae in childhood. The aims of this study were to assess the effects and outcomes on growth, neurodevelopmental status, and hearing in very low birth weight (VLBW) premature infants with postnatal CMV infection via breast milk at the corrected age of 12 and 24 months.The prospective follow-up study population comprised all living preterm children (n = 55) with a birth weight ≤1500 g and gestational age of ≤35 weeks, who had been participated in our "postnatal CMV infection via breast milk" studies in 2000 and 2009, respectively. The cohort of children was assessed at 12 and 24 months. Clinical outcomes were documented during hospitalization and after discharge. Long-term outcomes included anthropometry, audiologic tests, gross motor quotient, Infant International Battery, and neurodevelopmental outcomes; all were assessed at postcorrected age in 12 and 24 months during follow-up visits.Of the 55 infants enrolled in the study (4 noninfected infants were excluded because their parents did not join this follow-up program later), 14 infants postnatally acquired CMV infection through breast-feeding (infected group) and were compared with 41 infants without CMV infection (control group). No significant differences were observed between the groups with regard to baseline characteristics, clinical outcomes, anthropometry, or psychomotor and mental development on the Bayley scale of infant development. None of the infants had CMV-related death or permanent sensorineural hearing loss.Transmission of CMV from seropositive mother via breast milk to preterm infants does not appear at this time to have major adverse effects on clinical outcomes, growth, neurodevelopmental status, and hearing function at 12 and 24 months corrected age.

Transmission of cytomegalovirus from mothers to preterm infants by breast milk.

OBJECTIVES: To assess the risk of transmission of cytomegalovirus (CMV) by breast milk from CMV-seropositive mothers to their breast-fed preterm infants and to evaluate their outcome. PATIENTS AND METHODS: The study population comprised breast-fed preterm infants with a birth weight of <1,500 g and gestational age of <35 weeks. Venous blood samples from the mothers and infants were tested for CMV IgG and IgM antibodies on the 5th and 30th day after birth. Breast milk was obtained for CMV DNA detection by polymerase chain reaction and viral culture on the 5th day and on the 3rd, 6th and 12th week. Urine samples of the babies were collected at the same time for CMV culture. Neurodevelopmental assessment was done at 6 months of age, corrected for preterm birth. RESULTS: Thirty-eight mothers and 42 infants (including 4 sets of twins) were enrolled in the study. A mother-infant pair was excluded because of inadequate breast milk collection. Thirty-six mothers (97.3%) were CMV-seropositive. CMV DNA of breast milk was detected in 35 seropositive mothers. Six infants of 5 mothers were infected (infected group) at a mean of 77 days after birth, and 34 infants of 31 mothers were not (noninfected group). In all the mothers of the infected group, CMV virus could be cultured from the milk whey. The average maternal CMV IgG on day 5 after delivery was higher in the infected than in the noninfected group. Sepsis-like symptoms and hyperbilirubinemia were more frequently noted in the infected infants than in the noninfected, but the difference was not statistically significant. Neurodevelopmental outcome did not significantly differ between the 2 groups. CONCLUSIONS: The risk of CMV infection in breast-fed premature infants was highest when the mothers shed viable virus in their breast milk. These mothers had high CMV IgG, which may help identify those mother-infant pairs at risk. Inactivation of the virus in milk by freezing may be a way of reducing the transmission of this virus via breast milk.

High cytomegalovirus load and prolonged virus excretion in breast milk increase risk for viral acquisition by very low birth weight infants.

BACKGROUND: Breast milk is the main source of postnatal human cytomegalovirus (HCMV) infection. The aim of this study was to assess the relationship between HCMV load in breast milk and viral transmission to very low birth weight (VLBW) infants. METHODS: Breast-fed VLBW infants who were born to HCMV-seropositive mothers and who were managed in a neonatal intensive care unit were enrolled in the study. Blood from mothers and infants was tested for HCMV antibodies after birth. Breast milk was collected for viral culture and HCMV load measurement. Urine from the babies was obtained for HCMV-DNA detection. Symptoms of HCMV infection were recorded and evaluated by neonatologists. RESULTS: Of the 23 evaluated mothers during a 1-year period, 19 were HCMV seropositive; 17 of the women had detectable HCMV-DNA in their breast milk whey. Of the 23 infants born to the 19 seropositive mothers, 8 infants of 8 mothers had HCMV-DNA detected in the urine, indicating that they were infected, even though the breast milk was always frozen prior to feeding. Three infected infants had symptoms. At 4 weeks after delivery, the median viral load in breast milk from mothers of the 8 infected infants was significantly higher than that from mothers of the 15 noninfected infants (P = 0.04). HCMV was detectable in breast milk for a significantly longer period in mothers of infected infants (7.5 vs. 2.6 weeks P = 0.03). CONCLUSIONS: High HCMV load and prolonged virus excretion in breast milk are maternal risk factors for viral transmission to VLBW infants.