Dados do Trabalho

Título

ACUTE ENCEPHALOMYELITIS WITH WHITE MATTER CHANGES IN ARCN1-ASSOCIATED SYNDROME

Apresentação do caso único

A male preterm infant born at 32 weeks presented with global developmental delay, short stature, microcephaly, and severe bilateral myopia, along with optic disc hypoplasia. He also had bilateral inguinal hernia and cryptorchidism, both corrected at 4 months of age. Dysmorphic features on physical examination included ptosis, a flattened nasolabial fold, and retrognathia. At one year old, he developed hepatitis of unknown etiology. From age two, he experienced intermittent focal deficits, including ataxia, paraparesis, and drowsiness, typically triggered by viral respiratory infections. Neuroaxis MRIs revealed diffuse white matter abnormalities, including in the bilateral semioval center, peritrigonal areas, corpus callosum, and white matter of both cerebral hemispheres, characterized by T1 hypointensity and T2/FLAIR hyperintensity. Diffuse sequelae were also noted in the spinal cord parenchyma, with a more confluent pattern from C4 to T6, suggestive of demyelinating events. Acute episodes were managed successfully with methylprednisolone pulse therapy. Given the dysmorphisms and the complex medical history, a leukodystrophy panel was performed at 3 years and 10 months, revealing a pathogenic heterozygous variant in the ARCN1 gene (c.1099C>T, p.Gln367*).

Discussão

The ARCN1 gene, located on chromosome 11q23.3 (OMIM 600820, MedGen UID: 934653), is associated with a syndrome characterized by short stature, micrognathia, and global developmental delay, among other phenotypic features. Common characteristics include prematurity, microcephaly, and genitourinary malformations in males. Transient hepatic dysfunction, glycosylation abnormalities, giant cell hepatitis, hepatoblastoma, and cataracts have also been reported. Phenotypic severity varies widely, from relatively mild presentations to intrauterine or perinatal death.

Comentários finais

Acute encephalomyelitis with white matter changes in ARCN1-associated syndrome has not been documented in the literature but was observed in this patient. This presentation is likely linked to glycosylation defects inherent to the syndrome. Genetic knowledge of the patient’s condition facilitated appropriate management of acute episodes.

Referências

Izumi K, Brett M, Nishi E, Drunat S, Tan ES, Fujiki K, Lebon S, Cham B, Masuda K, Arakawa M, Jacquinet A. ARCN1 mutations cause a recognizable craniofacial syndrome due to COPI-mediated transport defects. The American Journal of Human Genetics. 2016 Aug 4;99(2):451-9. Tidwell T, Deshotel M, Palumbos J, Miller C, Bayrak-Toydemir P, Carey JC. Novel de novo ARCN1 intronic variant causes rhizomelic short stature with microretrognathia and developmental delay. Molecular Case Studies. 2020 Dec 1;6(6):a005728. Ritter AL, Gold J, Hayashi H, Ackermann AM, Hanke S, Skraban C, Cuddapah S, Bhoj E, Li D, Kuroda Y, Wen J. Expanding the phenotypic spectrum of ARCN1-related syndrome. Genetics in Medicine. 2022 Jun 1;24(6):1227-37.

Palavras Chave

arcn1; demyelinating disease; Developmental delays