Table 6.

Clinical findings associated with defects in CNTNAP2

CNTNAP2	Sex & Age	ID	Speech	Age of Walking	Seizures age of onset	Birth parameters Weight, Heigth, OFC	Weight Height OFC	Behavioral anomalies/ Stereotypies	Facial dysmorphisms	Other findings
C1	f, 8y	Severe	none	2y with aid, lost this function (3y)	yes, resist. to treatment	2430 g 45 cm not reported	<P3 <P3 <P3	hand movements	synophrys, long eyelashes, prominent columella, short philtrum, arched palate, widely spaced teeth, prominent jaw	happy, affectionate, TOF, pyloric stenosis, vesicoureteric reflux, agenesis of labia minora, hirsutism, tapering fingers
C2	m, 18y	Severe	?	?	complex, early onset	?	?	?		hyperbreathing, apnoe episodes
C3	f, 11y	Severe	few words, lost this function	2,5y, lost this function	3y	3510 g	P10 <P3 P10	yes	broad mouth, protruding tongue	develop. regression from 15 m, swallowing problems, nocturnal laughing, scoliosis, spastic tetraparesis, hyperreflexia, constipation, hyperbreathing
C4 Zweier et al., 2010 [28]	f, 7y	Profound	none	no	3-6mo	3400 g	P5 <P2 P50	yes	broad forehead, prominent ear lobes, widely spaced teeth, tented upper lip	exotropia, heterochromasia, high pain threshold, cold feet, sleeping problems, joint hyperlaxity
C5	f, 2y 8mo	Profound	none	no, no crawling	none	4030 g 53 cm 38 cm	P75 P25-50		high arched palate, upslanting palpebral fissures, small teeth, prominent forehead	septo-optical dysplasia, MRI: agenesis of septum pellucidum
C6	f, 8y	Profound	none	no	yes, resist. to treatment	1160 g 35 cm 28 cm	<P3 <P3 <P5		mild synophrys, low set, large ears, fleshy ear lobes, thin upper lip, low frontal hairline	birth at 29th week of gestation, blindness, hydrocephalus, ductus arteriosus, syndactyly toes 2-3, hypotonia, spasticity of legs, obstipation, liquid uptake by PEG tube
C7	f, 8y	moderate to severe	simple	15mo	none	3860 g 54 cm 34 cm	P25-P50 P50 <P5	suspected in infancy	epicanthal folds, tented upper lip, short columella, bulbous nose	overfriendliness, pubertas praecox, delayed bone age, retentive memory, excessive empathy, autoagressive behavior, flat feet
published biallelic defects N = 13 [24,25]	2x f, 1x m, 10x not reported, 1-20y	Severe	2x no, 1x single words [26], 10x yes, but regression [24,25]	2x normal, 1x not known [26], 10x 16mo-30mo [24,25]	13x yes, 4mo-30mo	not reported	<P3-normal not reported <P3-P99	8x yes [24,26], 1x tooth grinding and repetitive hand movements [26]	2x wide mouth and thick lips [26]	1x dry skin, 1x regression, 1x cerebellar hypoplasia, 3x hyperbreathing [26], 10x developmental regression with onset of seizures, 9x decreased deep tendon reflexes [24,25], 4x MRI: cortical dysplasia [24], 1x MRI: leukomalacia, 1x hepatosplenomegaly [25]
published heterozygous defects N = 12 [1,3,7,12,21,33]		6x not reported [1,3,21], 1x normal [7], 2x mild-moderate [3,7], 3x severe [7,12,33]	6x not reported [1,3,21], 1x normal [7], 3x speech impairment [7,12] 2x no [7,33]	11x not reported [1,3,7,12,21], 1x no [33]	5x not reported [1,3], 2x no [12,33], 5x yes [3,7,21], 0y-34y	not reported	not reported	8x yes [1,3,7]	not reported	1x multiple congenital malformations [33], 1x Gilles de la Tourette syndrome [12], 3x Schizophrenia [7]

TOF, tetralogy of Fallot; f, female; m, male; y, year; mo, month; ASD, autism spectrum disorder; published reports on CNTNAP2 and NRXN1: only papers containing clinical data are cited; ass., associated; P, centile; ass., associated