SZT2 disease, also known as Early Infantile Epileptic Encephalopathy-18 (https://omim.org/entry/615463), is a very rare genetic condition that occurs when a child carries two bad copies of the SZT2 gene, typically inherited by chance from unrelated parents. The gene was first discovered in 2009 (1), the 2nd in a series of laboratory mice bred to have a low seizure threshold (more susceptible; hence the gene name i.e. Seizure Threshold 2). From 2013 to 2020, multiple reports of children with this genetic condition began to appear in the literature, most with independent SZT2 mutations (2, 3, 6-15). The physiological role of the SZT2 protein only began to emerge in 2017 with two studies (4, 5) showing that SZT2 forms a novel complex (called “KICSTOR”) that regulates (keeps in check) a molecular signaling pathway called mTOR (https://en.wikipedia.org/wiki/MTOR), known to be important for cell growth and survival and implicated in several medical conditions, including cancer and other neurological diseases such as tuberous sclerosis. While literature on SZT2 itself is still limited, the common clinical features (intractable seizures and distinct neuroradiological anomalies) and emerging ideas about its normal function provides hope that effective therapies will be developed.
ABOUT THE DISEASE
The following are some (not all) common symptoms noted in patients with SZT2:
One of the most common features of this disease is seizures that do not respond well to available medications.
The first seizures usually occur between 3 months and 3 years of age.
Infantile spasms at first year of age is possible (WEST SYNDROME)
Seizures are often drug resistant and difficult to control.
Hypotonia (low muscle tone)
Macrocephaly (large head)
Loss of milestones or regression with increased seizures
Mild to severe cognitive/intellectual delay
Mild to severe delayed development
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