MedGen

Developmental and epileptic encephalopathy-8 (DEE8) is an X-linked disorder characterized by seizure onset before 2 years of age and severe developmental delay. Some patients have hyperekplexia (summary by Shimojima et al., 2011). For general phenotypic descriptions and discussions of genetic heterogeneity of developmental and epileptic encephalopathy and hyperekplexia, see DEE1 (308350) and HKPX1 (149400), respectively. [from OMIM]

A hereditary neurological disorder with characteristics of excessive startle responses. The disease manifests shortly after birth with violent jerking to noise and touch, and massive and sustained stiffening of the trunk and limbs, clenching fists, and attacks of a high frequency trembling. Motor milestones are often mildly delayed, but intellectual development is usually normal. Mutations in the GLRA1 gene (5q32) are found in about 30% of patients. These mutations are transmitted as an autosomal dominant or recessive trait. The GLRA1 gene encodes the alpha1 subunit of the juvenile neuronal receptor for the inhibitory neurotransmitter, glycine. Mutations of this subunit cause a variety of dysfunctions of the neuronal chloride (Cl-) channel. Mutations in the GLRB, GPHN and SLC6A5 genes (4q31.3, 14q24 and 11p15.2-p15.1) have also been observed. [from SNOMEDCT_US]