Table 2.

Catatonic features in individuals with 22q11.2 deletion syndrome.

Case	Age, y; Sex	Intellect	Lifetime history of seizure disorder	Lifetime history of other neurological/ motor issues	Psychiatric disorders (AAO, y)	Catatonia			Medications at last assessment
						AAO, y	Features of catatoniaa,b	Course and response to treatment	Antipsychotic	Other neuropsychiatric
Current case series
1	19, M	Mild ID	-	-	SZ (18), SAD and OCD (14), GAD (12) with panic attacks	~14	b Stupor, mutism, not eating	Good response to antipsychotic	risperidone	escitalopram
2	17, M	Mild ID	-	-	SZ (16), MDD (16)	16	a Stupor, agitation, mutism, negativism, verbal stereotypy	Decreased catatonic features with increased dosage of antipsychotic	risperidone	valproic acid
3	18, F	DD	-	Tremors, dyskinesia, insomnia, cognitive decline	PNOS (16)	16	Mutism, not eating	Good response to antipsychotic; Limited response at age 16 y to steroid and IVIG therapy, for suspected autoimmune encephalopathy	risperidone	lorazepam, experimentald
4	21, F	BL-mild ID	Generalized seizures	-	MDD (12), GAD (12), panic disorder	16	Stupor	Gradual reduction in symptoms without any specific treatment	-	sertraline, zoplicone
5	33, F	Mild ID	-	Tardive choreiform movements, akathisia	SZ (14)	19	b Posturing, stereotypies	Good response to antipsychotic	risperidone, paliperidone	lorazepam
6	22, F	NVLD	-	Antipsychotic-induced tremors, akathisia, and acute dystonia	SZA (BP type, 21), GAD (16)	22	a Stupor, negativism, motor stereotypies, not eating	Good response to antipsychotic	risperidone	valproic acid
7	22, M	Mild ID	-	Restless legs syndrome, tremors, stiffness	SZ (21)	22	b Stupor, mannerisms, altered arousal with eyes closed	Catatonic and floridly psychotic at last assessment	lurasidone	clonazepam
8	38, F	Mild ID	-	Bilateral tremor (hands)	SZA (22), SAD	22	b Stupor, negativism, self-injury, not eating	On antipsychotic gradual improvement over time	olanzapine	valproic acid
9	28, F	Mild ID	-	Tremor (hand), myoclonic jerks (arms), tardive dyskinesia	SZ (21), OCD (22)	>22	a Waxy flexibility, mutism, negativism, posturing, mannerisms, motor and verbal stereotypies	Catatonic and psychotic symptoms at last assessment	paliperidone	fluvoxamine, clonazepam
10	40, F	BL	Generalized seizures	Recurrent oculogyric crises	SZ (21), MDD (19)	~25	Psychomotor agitation “bordering on catatonic excitement”	Dramatic improvement with ECT and antipsychotic	quetiapine	citalopram, bupropion, lorazepam
11	34, F	BL	Generalized seizures	Tremors, cogwheel rigidity, marked speech degradation (slurring, mumbling), query PD/DIP	SZ (15)	<34	a Stupor, mutism, grimacing, echophenomena, self-injury, not eating	Catatonic and floridly psychotic symptoms at last assessment	chlorpromazine,zuclopenthixol	valproic acid, benztropine
12c	50, M	BL-mild ID	Generalized seizures	PDb (diagnosed age 48 years), dystonia	SZ (18)	45	b Stupor, stereotypies (possible), lethargy, NMS (suspected)	Good response to levodopa/carbidopa; Limited response previously to ECT	-	levodopa/carbidopa, entacapone, pramipexole, fluoxetine, amitriptyline, clonidine, zoplicone, lorazepam
13	60, F	Mild ID	-	Mild facial hemiparesis, rigidity, dysphagia, antipsychotic-induced dystonia, orofacial dyskinesias, query Lewy body disease	SZA (57)	~60	b Posturing, stereotypies, NMS (suspected)	Ongoing, as are the psychotic symptoms	olanzapine	venlafaxine, trazodone
Published case reports
Usiskin et al., 1999	15, F	BL	NR	Dystonic reaction to risperidone	SZ (12)	12	a Waxy flexibility, stupor, mutism	Good response to antipsychotic	olanzapine	NR
Faedda et al., 2015	15, F	Mild ID	-	Tics, bradykinesia (AAO 12)	PNOS (14), OCD (12), Anxiety	14	a Stupor, agitation, mutism, negativism, posturing, grimacing, echolalia,,self-injury, incontinence, not eating	Good response of catatonic features to lorazepam; Partial response of psychotic illness to olanzapine, ziprasidone; No response at age 14 y to IVIG therapy for suspected autoimmune encephalopathy, or age 12 to 14 y to several psychotropic/antiparkinsonian medications (none antipsychotic)	ziprasidone	lorazepam
Graf et al., 2001	18, F	NR	NR	NR	PNOS (<18)	NR	“Catatonia”, agitation	Good response to antipsychotic and experimental drugc	quetiapine	Experimental drugc
Sachdev et al., 2002	22, M	Mild-mod ID	Generalized seizures	Myoclonic jerks	PNOS (19)	19	a Posturing, stereotypies, grimacing	Fair to good response to antipsychotic	olanzapine	carbamazepine, clonazepam
Sieberer et al., 2005	22, F	Mild ID	NR	NR	PNOS (22)	22	b Stupor, mutism	Good response to lorazepam and antipsychotic	risperidone	NR

Abbreviations: AAO, age at onset; BL, borderline; BP, bipolar; DD, developmental delay; DIP, drug-induced parkinsonism; ECT, electroconvulsive therapy; F, female; GAD, generalized anxiety disorder; ID, intellectual disability; IVIG, intravenous immunoglobulin; M, male; MDD, major depressive disorder; mod, moderate; NMS, neuroleptic malignant syndrome; NR, not reported; NVLD, non-verbal learning disability; OCD, obsessive compulsive disorder; PD, Parkinson’s disease; PNOS, psychotic disorder not otherwise specified; SAD, social anxiety disorder; SZ, schizophrenia; SZA, schizoaffective disorder; y, years

^aMet criteria for a diagnosis of catatonia based on retrospectively-applied DSM-5 criteria. See text for details.

^bMet two of 12 criteria for DSM-5 catatonia. See text for details.

^cCase 12: Previously published in Parkinson’s disease case series [Butcher et al., 2015a; Butcher et al., 2013]

^dExperimental drugs: Case 3, minocycline [Dean et al., 2012]; Case in Graf et al., 2001, metyrosine (alpha-methyl-para-tyrosine), a competitive inhibitor of tyrosine hydroxylase, the rate-limiting enzyme of catecholamine synthesis [Bloemen et al., 2008].

NB. All but two of the 13 cases in the new case series had a history of at least one endocrine disorder (hypocalcemia, n=9; hypoparathyroidism, n=6; hypothyroidism, n=4; type 2 diabetes, n=4; hypomagnesium, n=3; data not shown), consistent with the multisystem nature of 22q11.2DS [Fung et al., 2015].