Dados do Trabalho

Título

Development delay, impaired growth, dysmorphic facies, and axonal neuropathy (DIGFAN) with epilepsy: case report

RESUMO

Case presentation:
LSG, 31 years-old man, presented development delay (motor and cognitive), short stature, dysmorphic facial features, deafness and epilepsy since childhood. The brother had motor and intellectual impairment and his father progressive ataxia related to SCA 2. Neurologic exam revealed: short stature, facial dysmorphism (figure 1), hearing loss, incomprehensible sounds, comprehends some basic commands with gesture, no pyramidal nor cerebellar signs were documented. Brain MRI revealed white matter hyperintensities on T2 and FLAIR, brain and cerebellar atrophy and thinning of the brainstem. Auditory evoked potential showed bilateral involvement with peripheral topography. The genetic test showed a pathogenic variant c.79G>A in the MORC2 gene.

Discussion:
MORC2 is a gene that through its ATPase activity is essential for epigenetic silencing. Mutation in this gene seems to cause a hyperactivation of silencing in neural cells, impairing neurological development [1]. These mutations have been reported most in Charcot-Marie-Tooth type 2Z and DIGFAN syndrome [2,3]. DIGFAN syndrome is characterized by development delay, short stature, hypotonia, cognitive impairment, dysmorphic facies, and axonal neuropathy. This syndrome can also present hearing loss and brain atrophy [4,5]. In the literature, patients with the c.79G>A variant are associated with developmental delay, growth retardation and abnormal brain MRI, as in our case. Epilepsy is not usually associated with DIGFAN syndrome in MORC2 mutation as in our case, being a rare manifestation of this phenotype.

Final comments:
Epilepsy should be considered as a manifestation of MORC2 spectrum (DIGFAN syndrome), depending on the variant. Some variant exerts a more intense action on neural silencing, resulting in more severe phenotypes related to central nervous system that could be involved in epileptic manifestation as in our case. [4].

Palavras Chave

DIGFAN syndrome ; MORC2 mutation; Epilepsy

Área

Neurogenética