. 2023 Aug 2;44(35):3357–3370. doi: 10.1093/eurheartj/ehad418

Table 3.

CALM cases with likely primary neurodevelopmental/neurological features and concomitant structural abnormalities and/or congenital heart diseases

Gene	Variant	Domain	Cardiological phenotype	Neurodevelopmental/neurological features	Structural abnormalities	Congenital heart diseases
*CALM1*	p.N98S (p.Asn98Ser)	EF-hand III, Ca²⁺-chelation loop	LQTS/CPVT	Autism	-	-
*CALM1*	p.N98S (p.Asn98Ser)	EF-hand III, Ca²⁺-chelation loop	CPVT	Mild intellectual disability, ADHD, epilepsy	-	-
*CALM1*	p.E105A (p.Glu105Ala)	EF-hand III, Ca²⁺-chelation loop	LQTS/CPVT	Developmental disorder with hyperactivity	-	-
*CALM1*	p.E105K (p.Glu105Lys)	EF-hand III, Ca²⁺-chelation loop	Atypical	Developmental delay, recurrent seizures (benign focal seizure susceptibility syndrome)	-	-
*CALM1*	p.D132V (p.Asp132Val)	EF-hand IV, Ca²⁺-chelating	LQTS	Autism, ADHD, language disorder, amblyopia	-	-
*CALM1*	p.E141V (p.Glu141Val)	EF-hand IV, Ca²⁺-chelation loop	LQTS	ADHD, dyslexia	Mildly impaired LV diastolic function, mild LA dilatation	-
*CALM1*	p.F142L (p.Phe142Leu)	EF-hand IV	LQTS	Autism, intellectual disability	Non-compaction cardiomyopathy	-
*CALM1*	p.F142L (p.Phe142Leu)	EF-hand IV	LQTS	Epilepsy, infantile spasms, EEG dysrhythmia	-	PFO, small aortopulmonary collateral from the distal arch
*CALM1*	p.F142L (p.Phe142Leu)	EF-hand IV	LQTS	Autism, intellectual disability, developmental delay, epilepsy, arachnoid cyst fenestration	-	ASD, ostium secundum
*CALM2*	p.T35I (p.Thr35Ile)	EF hand I	CPVT	Social communication disorder, gender dysphoria	-	-
*CALM2*	p.E46K (p.Glu46Lys)	EF hand II	CPVT	Autism, epilepsy with abnormal EEG	-	PDA
*CALM2*	p.E46K (p.Glu46Lys)	EF hand II	CPVT	Autism, severe intellectual disability	-	PDA
*CALM2*	p.T63R (p.Thr63Arg)	EF-hand II, Ca²⁺-chelation loop	UD	Seizures	Dilated cardiac cavities at autopsy	-
*CALM2*	p.I64M (p.Ile64Met)	EF-hand II, Ca²⁺-chelation loop	Absent	Malformation-neurodevelopmental disorder syndrome: jejunal membranous atresia, neurodevelopmental disorder, generalized joint laxity, some dysmorphic features	-	-
*CALM2*	p.N98I	EF-hand III, Ca²⁺-chelation loop	LQTS	ADHD, dyslexia, dyspraxia	Concentric LV hypertrophy
*CALM2*	p.N138K (p.Asn138Lys)	EF-hand IV, Ca²⁺-chelation loop	LQTS	Mild intellectual disability, ADHD, Rolando focus at EEG	HCM	-
*CALM3*	p.D96H (p.Asp96His)	EF-hand III, Ca²⁺-chelation loop	LQTS	Autism, developmental delay	-	PDA
*CALM3*	p.N138K (p.Asn138Lys)	EF-hand IV, Ca²⁺-chelation loop	LQTS	Psychiatric disorders	-	-
*CALM3*	p.E141G (p.Glu141Gly)	EF-hand IV, Ca²⁺-chelating	LQTS	Seizures	-	ASD
*CALM3*	p.F142L (p.Phe142Leu)	EF-hand IV	LQTS	Autism, developmental delay	RV hypertrophy & dilatation	VSD, aortic overriding

Cases with associated cardiac structural abnormalities are highlighted in grey.

ADHD, Attention deficit hyperactivity disorder; EEG, electroencephalogram; LV, left ventricle: LA, Left atrium; PFO, patent foramen ovale; ASD, atrial septal defect; PDA, patent ductus arteriosus; VSD, ventricular septal defect; RV, right ventricle; HCM, hypertrophic cardiomyopathy; LQTS, long QT syndrome; CPVT, catecholaminergic polymorphic ventricular tachycardia; UD, uncertain diagnosis; CHD, congenital heart disease.