Severe retinopathy of prematurity is associated with reduced cerebellar and brainstem volumes at term and neurodevelopmental deficits at 2 years.

BackgroundTo evaluate the association between severe retinopathy of prematurity (ROP), measures of brain morphology at term-equivalent age (TEA), and neurodevelopmental outcome.MethodsEighteen infants with severe ROP (median gestational age (GA) 25.3 (range 24.6-25.9 weeks) were included in this retrospective case-control study. Each infant was matched to two extremely preterm control infants (n=36) by GA, birth weight, sex, and brain injury. T2-weighted images were obtained on a 3 T magnetic resonance imaging (MRI) at TEA. Brain volumes were computed using an automatic segmentation method. In addition, cortical folding metrics were extracted. Neurodevelopment was formally assessed at the ages of 15 and 24 months.ResultsInfants with severe ROP had smaller cerebellar volumes (21.4±3.2 vs. 23.1±2.6 ml; P=0.04) and brainstem volumes (5.4±0.5 ml vs. 5.8±0.5 ml; P=0.01) compared with matched control infants. Furthermore, ROP patients showed a significantly lower development quotient (Griffiths Mental Development Scales) at the age of 15 months (93±15 vs. 102±10; P=0.01) and lower fine motor scores (10±3 vs. 12±2; P=0.02) on Bayley Scales (Third Edition) at the age of 24 months.ConclusionSevere ROP was associated with smaller volumes of the cerebellum and brainstem and with poorer early neurodevelopmental outcome. Follow-up through childhood is needed to evaluate the long-term consequences of our findings.

Increase in treatment of retinopathy of prematurity in the Netherlands from 2010 to 2017.

PURPOSE: Compare patients treated for Retinopathy of Prematurity (ROP) in two consecutive periods. METHODS: Retrospective inventory of anonymized neonatal and ophthalmological data of all patients treated for ROP from 2010 to 2017 in the Netherlands, subdivided in period (P)1: 1-1-2010 to 31-3-2013 and P2: 1-4-2013 to 31-12-2016. Treatment characteristics, adherence to early treatment for ROP (ETROP) criteria, outcome of treatment and changes in neonatal parameters and policy of care were compared. RESULTS: Overall 196 infants were included, 57 infants (113 eyes) in P1 and 139 (275 eyes) in P2, indicating a 2.1-fold increase in ROP treatment. No differences were found in mean gestational age (GA) (25.9 ± 1.7 versus 26.0 ± 1.7 weeks, p = 0.711), mean birth weight (791 ± 311 versus 764 ± 204 grams, p = 0.967) and other neonatal risk factors for ROP. In P2, the number of premature infants born <25 weeks increased by factor 1.23 and higher oxygen saturation levels were aimed at in most centres. At treatment decision, 59.6% (P1) versus 83.5% (P2) (p = 0.263) infants were classified as Type 1 ROP (ETROP classification). Infants were treated with laser photocoagulation (98 versus 96%) and intravitreal bevacizumab (2 versus 4%). Retreatment was necessary in 10 versus 21 (p = 0.160). Retinal detachment developed in 6 versus 13 infants (p = 0.791) of which 2 versus 6 bilateral (p = 0.599). CONCLUSION: In period 2, the number of infants treated according to the ETROP criteria (Type 1) increased, the number of ROP treatments, retinal detachments and retreatments doubled and the absolute number of retinal detachments increased. Neonatal data did not provide a decisive explanation, although changes in neonatal policy were reported.

Biallelic variants in POLR3GL cause endosteal hyperostosis and oligodontia.

RNA polymerase III (Pol III) is an essential 17-subunit complex responsible for the transcription of small housekeeping RNAs such as transfer RNAs and 5S ribosomal RNA. Biallelic variants in four genes (POLR3A, POLR3B, and POLR1C and POLR3K) encoding Pol III subunits have previously been found in individuals with (neuro-) developmental disorders. In this report, we describe three individuals with biallelic variants in POLR3GL, a gene encoding a Pol III subunit that has not been associated with disease before. Using whole exome sequencing in a monozygotic twin and an unrelated individual, we detected homozygous and compound heterozygous POLR3GL splice acceptor site variants. RNA sequencing confirmed the loss of full-length POLR3GL RNA transcripts in blood samples of the individuals. The phenotypes of the described individuals are mainly characterized by axial endosteal hyperostosis, oligodontia, short stature, and mild facial dysmorphisms. These features largely fit within the spectrum of phenotypes caused by previously described biallelic variants in POLR3A, POLR3B, POLR1C, and POLR3K. These findings further expand the spectrum of POLR3-related disorders and implicate that POLR3GL should be included in genetic testing if such disorders are suspected.