PEHO syndrome caused by compound heterozygote variants in ZNHIT3 gene.

PEHO syndrome is characterized by Progressive Encephalopathy with Edema, Hypsarrhythmia, and Optic atrophy, which was first described in Finnish patients. A homozygous missense substitution p.Ser31Leu in ZNHIT3 was recently identified as the primary cause of PEHO syndrome in Finland. Variants in ZNHIT3 have not been identified in patients with PEHO or PEHO-like syndrome in other populations. It has therefore been suggested that PEHO syndrome caused by ZNHIT3 variants does not occur outside of the Finnish population. We describe the first patient outside Finland who carries compound heterozygous variants in ZNHIT3 gene causing PEHO syndrome. Trio genome sequencing was carried out and the identified variants were confirmed by Sanger sequencing. The patient filled all diagnostic clinical criteria of PEHO syndrome. We identified biallelic missense variants in ZNHIT3 gene: the c.92C > T p.(Ser31Leu) variant (NM_004773.3), which is described previously as causing PEHO syndrome and the second novel variant c.41G > T p.(Cys14Phe). There are only eight heterozygous carriers of c.41G > T variant in the gnomAD database and it is predicted damaging by multiple in silico algorithms. The ZNHIT3-associated PEHO syndrome exists outside of the Finnish population.

Fatal neonatal stroke from a prenatal cardiac thrombus.

Despite careful investigation, the etiology of many perinatal arterial strokes is unknown. We report on a 5-day-old boy with a cardiac thrombus of prenatal origin resulting in a fatal postnatal stroke. The thrombus was discovered only at autopsy, challenging the assumption of a placental source of embolus in perinatal strokes in the absence of macroscopic and microscopic examination of the heart.

Neonatal citrullinemia: comparison of conventional MR, diffusion-weighted, and diffusion tensor findings.

Conventional MR, diffusion-weighted, and diffusion tensor imaging were performed in an 8-day-old girl with citrullinemia. She had severe hyperammonemia for several days. On conventional T2-weighted MR images, symmetric, confluent high signal intensity was found in the bilateral thalami, basal ganglia, cortex, and subcortical white matter. Diffusion-weighted imaging demonstrated decreased apparent diffusion coefficient in these areas, reflecting cytotoxic edema. Follow-up MR imaging at the age of 4 months revealed subcortical cysts, ulegyric changes, and atrophy, which were most prominent in the occipital lobes. Diffusion tensor imaging revealed decreased anisotropy throughout the brain, consistent with diffuse injury to the oligodendro-axonal unit. Diffusion-weighted and diffusion tensor imaging are valuable techniques for the detection of irreversible brain damage and for the characterization of hyperintense lesions on T2-weighted MR images in patients with the neonatal form of citrullinemia.

Arginase deficiency with lethal neonatal expression: evidence for the glutamine hypothesis of cerebral edema.

We describe a rare and lethal case of arginase deficiency in a 2-day-old female infant with encephalopathy and cerebral edema. The levels of glutamine and arginine but not ammonia were markedly elevated, lending support to the "glutamine hypothesis" as the mechanism of cerebral edema in urea cycle defects.

Ventriculomegaly and pericerebral CSF collection in the fetus: early stage of benign external hydrocephalus?

BACKGROUND AND PURPOSE: Mild ventricular dilatation or an asymmetric aspect of the atrium with prominent subrachnoid spaces is a challenging clinical condition in utero that requires prenatal MRI to rule out a destructive lesion or brain malformation. We report five cases that demonstrated benign external hydrocephalus postnatally, together with the prenatal MRI to define prenatal criteria of so-called benign external hydrocephalus. METHODS AND RESULTS: The prenatal MR images of five cases showing typical features of external hydrocephalus postnatally were reviewed. All cases showed in utero mild ventricular dilatation at the level of the atrium with enlargement of the subarachnoid spaces homo-, contra- or bilaterally, and predominantly in the parietooccipital areas. The head circumference was normal in all cases with no family history of macrocephaly. MRI did not demonstrate either abnormal signal within brain parenchyma or loss of the normal layering of the developing brain. CONCLUSION: Posterior mild ventricular dilatation and prominent subarachnoid spaces in a posterior distribution can be considered an early stage of benign external hydrocephalus that is nicely illustrated by MRI.