Table 1.

Summary of the clinical, neuroimaging, and molecular findings in males with CDKL5 mutations (n=8)

Patient No.	1	2	3	4	5^**	6^**	7	8
ID#	LR03-031a1	LR04-421	LR04-409	LR03-121	LR11-421	LR11-048	LR05-277	LR11-420
Ethnicity	Caucasian	Caucasian	Caucasian	Caucasian	Somali	Caucasian	Caucasian	Caucasian
Age at last assessment	7.5y	6y	4y	14y	10m	2m	6y	4y
Seizure onset	4w	5.5w	8–10w	6w	6m	2m	2w	5.5w
Seizure types	ISS, T, MC, atonic (head drop)	T, ISS, GTC	ISS	ISS, MC, T	ISS, PS, multifocal	PS, ISS	T, TC, ISS, MC	T, ISS
Intractable epilepsy	+	+	+	+	+	+	+	+
EEG findings	HYPS, multifocal bursts of polyspike activity	HYPS	HYPS	Continuous bihemispheric epileptiform discharges	Multifocal epileptiform discharges, recorded generalized seizures	Slow background (5 Hz), multifocal discharges (max. posteriorly)	Slow, R sharp waves (1^st EEG); disorganized, slow, freq. sharp waves, multifocal discharges (last EEG)	Localization -related epilepsy, likely arising from the R frontocentral area
CBR-CBL atrophy	−	+	−	++	−	−	++	+
Last MRI	9y	4y	<4y	9y	nd	2m	6w	2y
Severe GDD	+	+	+	+	+	+	+	+
Tone	Mixed (appendicular spasticity, axial hypotonia)	Mixed (appendicular spasticity, axial hypotonia)	Hypotonia	Mixed (appendicular spasticity, axial hypotonia)	Hypotonia	Severe hypotonia	Severe hypotonia	Severe hypotonia
CVI	+	+	+	+	+	+	+	+
Earliest OFC –SD (age)	nd	0–1 (4m)	+2 (birth)	+2 (2m)	nd	1–2 (birth)	nd	nd
Last OFC – SD (age)	0–1 (7y)	−2.5 (9m)	nd	−1–2 (14y)	+1 (10m)	0–1 (2m)	−1–2 (10y)	0–1 (4y)
Postnatal MIC	−	+	nd	−	−	−	−	−
Abnormal movements	+	−	−	+	+	−	+	−
Other medical problems	GER (G-J tube), constipation, mild optic atrophy, mild scoliosis, mild facial DYSM	G-tube, sleep apnea (due to hypoventilation), mild facial dysmorphism, hypoplasticscrotum	Neutropenia, G-tube	GER, growth failure, recurrent aspiration pneumonia, choking and difficulties handling secretions	Dysphagia with aspiration pneumonia, on thick liquid diet	GER	Neurogenic bladder, G- tube fed, constipation	G tube-fed, chronic respiratory insufficiency, osteopenia
Outcome	Deceased	Alive	Alive	Alive	Alive	Alive	Alive	Alive
Mutation	c. 578A>G (exon 9) p.D193G	c. 513C>A (exon 8) p.Y171X	c.2413C>T (exon 17) p.Q805X	c.175C>T (exon 5) p.R59X	c.2593C>T (exon 18) p.Q865X	Ex 10-15del	Ex 3del	c.62A>G (exon 2) p.E21G
Type	Missense	Nonsense	Nonsense	Nonsense	Nonsense	Deletion	Deletion	Missense
Inheritance	Germline mosaicism	De novo	De novo	De novo	De novo	nd	De novo	De novo
Family history	Affected maternal half-sister^*	2 maternal SAB	2 maternal SAB	No known neurologic problems	No known neurologic problems	No known neurologic problems	No known neurologic problems	No known neurologic problems

Abbreviations: CBR: cerebral; CBL: cerebellar; CPK: creatine phosphokinase; CPS: complex partial seizures; CVI: cortical visual impairment; d: days; DD: developmental delay; DYSM: dysmorphic features; EEG: electroencephalographic; GDD: global developmental; delay; GER: gastro-esophageal reflux; GJ: gastro-jejunostomy tube; HYPS: hypsarrhythmia; ISS: infantile spasms; LG: Lennox-Gastaut; m: months; M: myoclonic; MIC: microcephaly; nd: no data; OFC: occipito-frontal circumference; PS: partial seizures; T: tonic; SAB: spontaneous abortion; SD: standard deviations; VNS: vagal nerve stimulator; w: weeks; y: years

Affected maternal half sister (assessed at 5.5 years) had seizures with onset was at 6–7 months of age consisting of eye fluttering and jerky movements of the arms. Initial EEG showed pre-hypsarrhythmic changes. She subsequently had brief complex partial seizures every 1–3 months that were well-controlled on one medication. She had severe developmental delay. She rolled over at one year of age and at 5.5 years had minor head control but was unable to sit independently and remained non-ambulatory. She vocalized without distinct words. She also has abnormal movements, teeth-grinding and breath-holding spells. The mother of these two siblings is asymptomatic.

^**

These two patients were also included in a recent report by our co-authors [32]