Table 1.

Clinical features of individuals with nontruncating CACNA1C variants.

Individual	P1	P2	P3	P4	P5	P6	P7	P8	P9	P10	P11	P12	P13	P14
Variants	p.Phe166Leu	p.Lys177Arg	p.Arg324Trp	p.Val403Met	p.Leu601Arg	p.Met611Thr	p.Leu614Arg	p.Leu614Pro	p.Leu657Phe	p.Ile743del	p.Val1187Ala	p.Leu1408Val	p.Val1411Leu	p.Val1411Leu
	c.496T>C	c.530A>G	c.970C>T	c.1207G>A	c.1802T>G	c.1832T>C	c.1841 T>G	c.1841T>C	c.1969C>T	c.2227_2229delATC	c.3560T>C	c.4222C>G	c.4231G>C	c.4231G>T
Inheritance	de novo	de novo	de novo	de novo	de novo	de novo	de novo	de novo	de novo	de novo	de novo	de novo	de novo	de novo
Age at most recent exam	23 years	7.6 years	9 years	2.3 years	4 years	4 years	2.5 years	24 years	15 years	3.5 years	1.5 years	6.8 years	7.8 years	10 months
Sex	Female	Female	Female	Female	Female	Male	Male	Male	Female	Male	Male	Female	Female	Male
Development
Motor delay	+	+	+	+	+	+	+	+	+	+	+	+	+	+
Ambulatory (age started walking)	+ (16 months)	+ (15 months)	+ (21 months)	−	+ (28 months)	+ (17 months)	+ (3 years)	−	+ (2 years)	−	−	−	−	−
Abnormal Muscle tone	Hypotonia	−	Hypotonia	Hypotonia	Hypotonia	Hypotonia	Hypotonia	Hypotonia	−	Hypotonia, Leg spasticity	Hypotonia	Hypotonia	Hypotonia	Hypotonia
Abnormal balance/coordination	−	+	−	−	+	+	+	N/A	−	N/A	N/A	N/A	N/A	N/A
Tremor	−	−	−	Action tremor in arms in first 2 years, subsequently resolved	Intention tremor in arms, head tremor	−	−	−	−	−	−	−	−	−
Language delay	+	−	−	+	+	+	+	+	+	+	+	+	+	+
Verbal Ability	−	+	+	−	−	+	−	−	+	−	−	−	−	N/A
Clinical Diagnosis of Autism	−	−	−	−	−	−	−	+	−	−	−	−	−	−
ADHD	−	−	−	−	−	−	−	−	−	−	−	−	−	−
Cognition	Severe intellectual disability	Learning disability	Learning disability, dyslexia	Mild-moderate global developmental delay	Mild intellectual disability	Mild global developmental delay	Severe developmental delay	Intellectual disability, severity unspecified	moderate-severe intellectual disability	Severe global developmental delay	Unknown	Severe intellectual disability	Severe intellectual disability	Severe global developmental delay
Epilepsy
Seizures	+	+	+	−	−	+	+	+	+	−	+	+	+	+
Age of onset	6 years	11 months	8 years	N/A	N/A	7 months	10 months	1 year	6 years	N/A	1 year	6 months	11 months	2 months
Seizure types/Epilepsy syndrome	Absence, generalized tonic-clonic	Focal motor, absence. Seizures fever sensitive.	Focal seizures	N/A	N/A	West syndrome/ Infantile spasms	Myoclonic seizures; generalized tonic-clonic	Generalized epilepsy. Seizures are fever sensitive.	Behavioral arrest spells +/- head or limb jerking	N/A	Seizures provoked by fever, diagnosed as febrile seizures	Myoclonic seizures àmultiple generalized seizure types/ generalized epilepsy syndrome.	West syndrome/Infantile spasms à Lennox-Gastaut syndrome	Generalized epilepsy
Cardiac abnormalities
Abnormal ECG/Holter	N/A	−	−	−	N/A	−	−	−	−	−	N/A	Possible ventricular conduction delay	Prolonged QT	− (borderline QTc 450msec)
Abnormal ECHO	N/A	N/A	−	Small interatrial communication in the upper part of the atrial septum with left-right shunt	N/A	−	N/A	−	N/A	−	−	Trace AI, trivial TR, trace PR	−	− (previously known PDA/PFO have since closed)
Orthopedic abnormalities	Pes plagovalgus	Congenital hip dysplasia	Hypermobility	Left hip dislocation and right hip subluxation, joint hypermobility	Pes planovalgus, joint hypermobility, toe-walking	−	Bilateral clubfoot, and adducted thumbs	Kyphosis	Small appearing feet, tapered fingers	Bilateral clubfoot, prominent heels in small appearing feet, adducted thumb, and camptodactyly of fingers, tapering fingers	Cutaneous 2–3 toe syndactyly and mild 3–4 finger syndactyly, congenital torticollis	Kyphoscoliosis, Coxa valga	−	Bilateral congenital hip dysplasia, toe 2–3 syndactyly bilaterally, bilateral adducted thumbs
Ophthalmological abnormalities	Unknown	−	Strabismus, hyperopia	Strabismus (non paralytic)	Myopia	−	Strabismus	Hyperopia, astigmatism	−	Severe hyperopia	Hyperopia, astigmatism, esotropia	Strabismus	Cortical visual impairment	−
Dysmorphic features	+	−	−	−	+	−	−	+	+	+	−	−	−	+