Table 1.

ANKS1B microdeletion probands display a spectrum of neurodevelopmental phenotypes

ID	EIN-1-1	EIN-1-2	EIN-1-3	EIN-2-1	TOR-1	TOR-2	GEN-1	DEC-1	DEC-2
Sex	46XY	46XX	46XY	46XX	46XY	46XY	46XX	46XY	46XX
Age	11	6	3	5	7	2	3	7	8
Variant/deletion (GRCh37/hg19)	12:99609297-99986120	12:99609297-99986120	12:99609297-99986120	12:99930346-100284065	12:100099666-100230043	12:100112323-100192972	12:99945859-100303670	12:99727586-100152135	12:99994978-100105971
Variant detection	CMA/WES	CMA	CMA	CMA/WES	WGS	WGS	CMA/WES	CMA	CMA
Inheritance	Paternal	Paternal	Paternal	Paternal	Paternal	Maternal	Unknown	Maternal	Paternal
Ethnicity	Caucasian	Caucasian	Caucasian	Caucasian	Caucasian	South Asian	Caucasian	Caucasian	Caucasian
Variant size	377 kb	377 kb	377 kb	354 kb	130 kb	80 kb	358 kb	425 kb	111 kb
Allele	Heterozygous	Heterozygous	Heterozygous	Heterozygous	Heterozygous	Heterozygous	Heterozygous	Heterozygous	Heterozygous
Craniofacial dysmorphism	Brachycephalic, round facies, prominent brow; midface hypoplasia	Brachycephalic, round facies, midface hypoplasia	Brachycephalic, midface hypoplasia, positional plagiocephaly	Round facies, prominent metopic suture, small right ear with slight cupping	None reported	None reported	Round facies, occipital flattening, upslanting palpebral fissure, enlarged tongue	Hypertelorism, preauricular pit, short nose, thick nasal alae	Synophrys, downslanting palpebral fissure, anteverted nares, short philtrum
Head circumference	92nd percentile	90th percentile	60th percentile	<3rd percentile	91st percentile	95th percentile	Not reported	50th percentile	2nd percentile
Intellectual disability	No	No	No	No	Yes	Yes	Yes	No	No
Developmental delay	Yes	Yes	Yes	Yes	No	No	Yes	No	Yes
ASD	Yes	No	No	No	Yes	Yes	Yes	No	Yes
ADHD	Yes	Yes	No	No	No	No	No	Yes	Yes
Other psychiatric	Aggressive behavior, dysgraphia, self-soothing behaviors	Academic difficulty	Head banging	None	None	None	Poor play, eye contact, and name response; no imitation or pattern matching	None	Low frustration tolerance, reactive anger outbursts
Speech delay	Yes	Yes	Yes	Yes	Yes	Yes	Yes	No	Yes
Speech apraxia	No	Yes	No	Yes	No	No	Yes	No	No
Motor delay	Yes	Yes	Yes	Yes	No	Yes	Yes	No	No
Motor dyspraxia	No	Yes	Yes	No	No	No	Yes	No	No
Other neurologic	Vocal/motor Tourette’s, hypersensitive sensory processing deficit	Encopresis	Plagiocephaly, sleep disturbance, congenital tortocollis, myoclonic jerks, hypertonicity	None	None	None	None	None	None
MRI	None	Hyperintensities in caudate nucleus, thin corpus callosum	Normal	None	None	Hyperintensity in left periventricular white matter, thin corpus callosum body	Dysgenesis of corpus callosum, absent splenium	None	Enlarged ventricles, thin corpus callosum
EEG	Normal	None	Normal	None	None	Normal	Normal	None	None
Other	Astigmatism, high palate	Astigmatism, high palate, asthma	Ear tubes, high arched palate, frenulectomy,	Choanal atresia, pulmonary artery stenosis, atrial shunting	None reported	None reported	None reported	Brachydactyly, short phalanx of finger, short toe	Specialized schooling required

Patients harboring heterozygous and monogenic microdeletions in the ANKS1B gene were identified at Albert Einstein College of Medicine (EIN), the Autism Speaks MSSNG project at the University of Toronto (TOR), the DECIPHER project (DEC), and the GeneMatcher online resource (GEN). Several individuals were diagnosed with autism (ASD) and ADHD, and most display speech and motor phenotypes, including delayed achievement of developmental milestones, speech apraxia, and motor dyspraxia. Craniofacial dysmorphisms and abnormal MRI findings were also reported in several families. Two probands had head circumference meeting criteria for microcephaly (<3rd percentile). Variant detection refers to the method employed to identify the deletions

CMA  chromosomal microarray analysis, WGS whole-genome sequencing, WES  Whole-exome sequencing