Table 2.

Electroclinical characteristics of typical and atypical RTT syndrome.

Typical RTT	CDKL5-Related Disorder	FOXG1 Syndrome
Clinical Stages	Electroclinical Stages	Epilepsy Features
Early onset phase (6–12 months): loss of acquired motor and language skills and purposeful hand movements Rapid destructive phase (1–3 y): autistic features, intellectual disability, hand stereotypies, abnormal gait/motor dysfunction, onset of abnormal respiratory patterns Stabilization phase (2–10 y): improvements in behavior, eye contact and hand function Late motor deterioration (>10 y): spasticity, dystonia, and scoliosis, loss of independent walking in ambulant patients EPILEPSY FEATURES Mean onset: 4.7 y Frequent FS, No specific seizure semiology	Stage I (Early epilepsy): IS; Tonic-vibratory seizure, followed by a clonic phase with series of spasms, gradually evolving into repetitive distal myoclonic jerks, lasting 2–4 min Onset: neonatal-4th month (median: 4 weeks) Stage II (EE): 6 months–3 years (median: 11 months) IS intermixed with brief tonic seizures profound DD, no language or motor development, massive hypotonia Stage III (Late multifocal and myoclonic epilepsy): ages: 2.5–11 y (median 7 y) drug-resistant epilepsy with tonic seizures and spasms, myoclonic jerks or atypical absences Or epilepsy remission Ages: 2.5–19 y (median 5 y)	Deletions and intragenic variants: epilepsy onset within the second year of life (mean: 22 months in [7]) various epilepsy types (focal impaired awareness, myoclonic, and bilateral tonic) rate of drug resistance is high Duplications: IS (mean age at onset: 7.4 months). Frequent focal seizures (onset: 5 months–6 years), often in association with spasms [8]. in a minority: later recurrence of tonic or myoclonic seizures
EEG	EEG	EEG:
Stage 1: N/posterior rhythms slowing Stage 2: rolandic IED (drowsiness, sleep). sleep architecture abnormalities (poor/absent spindles) Stage 3: abnormal background (posterior slowing, absent sleep figures); bilaterally synchronous bursts of pseudo-periodic delta and generalized rhythmic spikes in sleep Stage 4: abnormal, slow background (wakefulness and sleep), central and/or vertex theta (4–6 Hz), IED (multifocal spikes or sharp waves during wakefulness and generalized slow spike-wave complexes during sleep)	Stage I: Interictal: N/slow. Ictal: bilateral and synchronous flattening, followed by repetitive sharp waves and spikes Stage II: Typical/modified hypsarrhythmia, very slow, intermixed with focal spikes and polyspikes (F, C, O) Stage III: High-amplitude delta with pseudo-periodic bursts of high-amplitude S, PS, SW predominating over the C, T, T-O region	Deletions and intragenic variants: slow background, multifocal S and sharp waves, less frequently diffuse theta excess Duplications: hypsarrhythmia/modified hypsarrhythmia (onset) multifocal S-slowW, bursts of generalized S-slowW, or focal slowing intermixed with high-amplitude irregular S-slowW (follow-up)