Table 2.

Clinical features of the six individuals with intellectual disability harboring pathogenic DEAF1 variants

Subject		#1 (597158)	#2 (615391)	#3 (M2647) [Berger et al., 2017]	#4 (561320) [Wenge et al.,​ 2017]	#5 (563832)	#6 (538820)	Subjects reported in the literature (n = 10) [Vissers et al., 2010; Rauch et al., 2012; Vulto et al., 2014; Faqeih et al., 2014; Rajab et al., 2015; Gund et al.,​ 2016]
Profiles	DEAF1 variants*	p.Gly212Ser	p.Arg226Trp	p.Trp234Arg	p.Arg246Thr	p.Gln264Pro	p.Lys305del	p.Arg224Trp, p.Arg226Trp, p.Ile228Ser, p.Arg254Ser, p.Gln264Pro and p.(Gly292Profs*)
	Age at evaluation	15y	2y	4y	8y	12y	3y	2–20y
	Gender	F	M	M	F	F	F	8 M and 2 F
	Family history	N.A.	+	N.A.	N.A.	N.A.	+, Brother mild autism	6/10
Development abnormalities	ID	+	+	+	+	+	+	Moderate to severe ID (10/10)
	Motor delay	+	+	+	+	N.A.	+	Mild-to-moderate motor problem and developmental delay (10/10)
	Speech problems	Absent	N.A.	Expressive speech delay (non-verbal)	Speech delay	N.A.	Speech delay	Severe speech delay and severely affected expressive speech (10/10)
	Regression	+	N.A.	1y skill regression	N.A.	N.A.	N.A.	2/10
	Prenatal growth retardation	N.A.	N.A.	N.A.	Slight prenatal growth retardation	N.A.	N.A.	N.A.
Neurological abnormalities	Seizures	+	N.A.	+, normal EEG	Partial seizures	+	+	7/10
	Hypotonia	N.A.	+	+	N.A.	+	Central hypotonia	7/10
	Ataxia	N.A	N.A	Slight tremor	N.A	+	+	Abnormal walking pattern (4/10), involuntary movements and drooling (3/10), dyskinesia (3/10), brisk reflexes without spasticity (1/10)
	Sleeping problems	N.A.	N.A.	+	Episodic	N.A.	N.A.	Sleep problems (5/10)
	Hearing loss	N.A.	N.A.	N.A.	Mild low frequency hearing loss	N.A.	N.A.	2/10
	Other	N.A.	N.A.	N.A.	N.A.	N.A.	N.A.	High pain threshold (4/10)
Behavioral abnormalities	Autistic phenotype	+	N.A.	+, Repetitive behavior	+	+	+	6/10, Poor eye contact (4/10), repetitive behavior (4/10)
	Aggressive behavior	N.A.	N.A.	+	+	N.A.	N.A.	6/10
	Self-injurious behavior	N.A.	N.A.	+, Head banging, hits/bites self	+	N.A.	N.A.	1/10
	Others	N.A.	N.A.	Pica	N.A.	N.A.	N.A.	Mood swing and excessive irritability (7/10), happy predisposition (4/10), self-stimulatory behavior (4/10), hyperactivity (3/10), compulsive behavior (3/10), fascinations (2/10),
Dysmorphologies	Brain abnormality	Borderline macrocephaly	Microcephaly	OTC WNL, normal MRI	Brain MRI showed slightly low cerebellar tonsils and EEG showed left-sided central parietal interictal spikes	N.A.	N.A.	Microcephaly (3/10), bilateral and symmetrical white matter abnormalities (3/10), symmetric T2 lesions in the basal ganglia (2/10), abnormal brain MRI (1/10), volume loss of the corpus callosum and brainstem in MRI (1/10)
	Craniofacial abnormality	Mild dysmorphology	N.A.	Mild dysmorphology	Left-sided ear tag	+	N.A.	Straight eyebrows (4/10), full nasal tip (4/10), prominent chin (3/10), cupid’s bow in upper lip (3/10), full lower lip (3/10), high arched palate (2/10), triangular face (1/10), widow’s peak (1/10), flat face (1/10), frontal bossing (1/10), upslant (1/10), epicanthic folds (1/10)
	Skeletal abnormality	Mild dysmorphology, skeletal large hands	N.A.	Pes planus, mild 2–3 syndactyly, 4th toe overlaps, 3rd joint laxity	History of congenital left hip dislocation	N.A.	N.A.	Skin syndactyly in toes 2 and 3 (4/10), brachydactyly (2/10), fetal finger pads (2/10), clinodactyly (2/10), hyperlaxity (2/10), sacral dimple (2/10), flat feet (1/10), sandal gap (1/10)
	Others	N.A.	N.A.	N.A.	N.A.	N.A.	N.A.	Thin fair hair (3/10), low-set hairline (1/10), left nipple inverted (1/10), dry skin (1/10), scrotal raphe (1/10)
Additional phenotypes	Infections	N.A.	N.A.	Frequent otitis media		N.A.	N.A.	Recurrent infections (4/10)
	Feeding difficulties	N.A.	N.A.	Early feeding issues	N.A.	N.A.	N.A.	Feeding difficulties (3/10)
	Digestive abnormality	Gastroesophageal reflux	N.A.	Gastroesophageal reflux	Constipation	N.A.	N.A.	N.A.

Abbreviations: Y (years), F (female), M (male), fs (frame shift), ID (intellectual disability), OTC (orbitofrontal cortex) WNL (within normal limits), EEG (electroencephalogram), MRI (magnetic resonance imaging), N.A. (not available)

^*The DNA variant numbering system used in this study is based on human DEAF1 cDNA sequence (RefSeq NM_021008.3). Nucleotide numbering uses +1 as the A of the ATG translation initiation codon in the reference sequence, with the initiation codon as codon 1.