Figure - available from: Case Reports in Pediatrics
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Brain CT scan: diffuse calcifications involving both lobes as well as basal ganglia and extensive bilateral periventricular hypodensities.
Source publication
A pseudo-TORCH syndrome is a rare autosomal recessive disease characterized by intracranial calci cation and microcephaly, leading to spasticity and seizures, but the serology of TORCH infection is negative. We present a 4-day-old female patient with jaundice, abnormal movement, and convulsions who was found to be homozygous for the missense USP18...
Citations
... Aicardi-Goutières Syndrome (AGS) stands as a rare genetically inherited neuroinflammatory disorder impacting the brain, immune system, and skin, presenting progressively with symptoms such as dystonia/spasticity, hepatosplenomegaly, elevated liver enzymes, thrombocytopenia, chilblain-like skin lesions, and neurological abnormalities, including microcephaly, CSF lymphocytosis, and developmental delays [79][80][81]. These symptoms, reminiscent of TORCH congenital infections despite the absence of active viral infection, have led to the term "Pseudo-TORCH syndrome" for AGS. ...
... These findings commonly include the loss of white matter, particularly in the periventricular and deep white matter regions, as well as calcifications in the basal ganglia and dentate nuclei [79,81,85]. Additionally, the presence of ventriculomegaly and the thinning of the corpus callosum are frequently observed, contributing to the distinctive radiological profile that aids in distinguishing AGS from other neurological conditions [80]. ...
Leukodystrophies, a group of rare demyelinating disorders, mainly affect the CNS. Clinical presentation of different types of leukodystrophies can be nonspecific, and thus, imaging techniques like MRI can be used for a more definitive diagnosis. These diseases are characterized as cerebral lesions with characteristic demyelinating patterns which can be used as differentiating tools. In this review, we talk about these MRI study findings for each leukodystrophy, associated genetics, blood work that can help in differentiation, emerging diagnostics, and a follow-up imaging strategy. The leukodystrophies discussed in this paper include X-linked adrenoleukodystrophy, metachromatic leukodystrophy, Krabbe's disease, Pelizaeus-Merzbacher disease, Alexander's disease, Canavan disease, and Aicardi-Goutières Syndrome.
... A Aicardi-Goutières Syndrome (AGS) is a rare genetically inherited neuroinflammatory disorder that impacts the brain, immune system, and skin. AGS commonly presents progressively with clinical presentation including dystonia/spasticity, hepatosplenomegaly, elevated liver enzymes, thrombocytopenia, chilblain-like skin lesions, and neurological abnormalities including microcephaly, CSF lymphocytosis, developmental delays, and other neurological impairments [79][80][81]. These symptoms mimic TORCH congenital infections despite the absence of an active viral infection [80,82,83]. ...
... AGS commonly presents progressively with clinical presentation including dystonia/spasticity, hepatosplenomegaly, elevated liver enzymes, thrombocytopenia, chilblain-like skin lesions, and neurological abnormalities including microcephaly, CSF lymphocytosis, developmental delays, and other neurological impairments [79][80][81]. These symptoms mimic TORCH congenital infections despite the absence of an active viral infection [80,82,83]. Considering AGS is not of infectious origins, it is commonly referred to as Pseudo-TORCH syndrome. ...
... These findings commonly include loss of white matter, particularly in the periventricular and deep white matter regions as well as calcifications in the basal ganglia and dentate nuclei [79,81,85]. Additionally, the presence of ventriculomegaly and thinning of the corpus callosum are frequently observed, contributing to the distinctive radiological profile that aids in distinguishing AGS from other neurological conditions [80]. ...
Leukodystrophies, also known as demyelinating diseases, mainly affect the CNS. Clinical presentation of different types of leukodystrophies can be nonspecific and thus, imaging techniques like MRI can be used for a more definitive diagnosis. These diseases are characterized as cerebral lesions with characteristic demyelinating patterns, which can be used as differentiating tools. In this review, we talk about these MRI imaging findings for each leukodystrophy, associated genetics, blood work that can help differentiate, emerging diagnostics, and follow up imaging strategy. The leukodystrophies discussed in this paper include X-linked adrenoleukodystrophy, Metachromatic leukodystrophy, Krabbe’s disease, Pelizaeus-Merzbacher disease, Alexander’s disease, Canavan disease, and Aicardi-Goutières Syndrome.
... Their seizures were not controlled with valproic acid. As of now only symptomatic treatment is available for OCLN related epilepsy (Misk et al., 2022). In the current study, both patients of family EP-AS 02 with the c.1324G > T; p.(Glu442Ter) variant of OCLN may lack gene expression due to nonsense-mediated decay of the mRNA caused by the premature stop codon. ...
Introduction:
Neurodevelopmental disorders (NDD) are a diverse group of disorders that affect the development of the nervous system. Epilepsy is a common phenotypic aspect of NDD.
Methods:
We recruited eight consanguineous families from Pakistan which segregated recessively inherited NDD with epilepsy. Magnetic Resonance imaging (MRI) and Electroencephalogram (EEG) were completed. Exome sequencing was carried out for selected participants from each family. The exome data were analyzed for exonic and splice-site variants that had allele frequencies of less than 0.01 in public databases.
Results:
Clinical investigations determined that developmental delay, intellectual disability and seizures were manifested by most patients in early childhood. EEG findings were abnormal in the participants of four families. MRI revealed demyelination orcerebral atrophic changes in multiple participants. We identified four novel homozygous variants including nonsense andmissense variants in OCLN, ALDH7A1, IQSEC2 and COL3A1, segregating with the phenotypes in the participants of four families. Previously reported homozygous variants of CNTNAP2, TRIT1 and NARS1 were found in individuals from three families. Clinical utility was observed in directing treatment in case of patients with an ALDH7A1 variant which included pyridoxine administration and enabling accurate counseling about the natural history and recurrence risk.
Conclusion:
Our results add to the clinical and molecular delineation of very rare NDD with epilepsy. The high success rate of exome sequencing is likely attributable to the expectation of homozygous variants in patients of consanguineous families, and in one case, the availability of positional mapping data that greatly aided the variant prioritization.
