Table 1.

Clinical Features of Subjects with Biallelic OTUD6B Variants

	Family 1	Family 2	Family 3			Family 4		Family 5		Family 6
	II-2	II-2	II-2	II-4	II-5	II-3	II-4	II-1	II-2	II-1	II-2	II-3
Gender	female	male	male	male	male	male	male	female	female	male	male	female
Ethnic origin	Hispanic	Hispanic/Italy	Egypt	Egypt	Egypt	Syria	Syria	Palestine	Palestine	Turkey	Turkey	Turkey
Age at last examination	18 years, 2 months	17 years, 2 months	13 years (died same year)	8 years, 1 month	3 years	9 years, 5 months	3 years, 11 months	5 years, 4 months	3 years, 2 months	20 years, 7 months	16 years, 6 months	14 years, 8 months
Intellectual disability	severe	severe	severe	severe	severe	severe	severe	severe	severe	moderate	mild	moderate
Speech delay	no words	no words	no words	no words	no words	no words	no words	no words	no words	no delay	no delay	no delay
Seizure (onset)	+ (12 months)	+ (15 months)	+ (NA)	+ (NA)	+ (NA)	+ (17 months)	+ (3 years)	+ (7 months)	+ (2 years)	+ (18 months)	+ (7 years)	+ (8 years)
IUGR	+	+ (poor fetal activity)	+	+ (poor fetal activity)	+	+	+	−	−	−	−	−
Weight, kg (z-score)	28 (−8.9)	47.6 (−2.2)	15 (−2.2) (at 10 years)	12 (−4.5) (at 5 years)	9 (−3.5)	15.5 (−1.6) (at 5 years 2 months)	15 (−1)	15.6 (−1.4)	10 (−3.4)	67 (−0.33)	66 (0.27)	54 (0.27)
Height, cm (z-score)	129.5 (−5.2)	137 (−4.9)	103 (−5) (at 10 years)	90 (−3.8) (at 5 years)	80 (−3.7)	107 (−0.6) (at 5 years 2 months)	93 (−2.5)	100 (−2.1)	87 (−2.0)	176 (−0.1)	171 (−0.5)	159 (−0.4)
OFC, cm (z-score)	47.9 (−4.7)	52 (−2.8)	44.5 (−6.5) (at 10 years)	44 (−5.3) (at 5 years)	43 (−5.3)	46.5 (−3.5) (at 5 years 2 months)	45 (−4.3)	45 (−4.5)	44 (−4.3)	55.7 (−0.35)	54.5 (−0.59)	54.3 (0.38)
Hypotonia	+	+	+	+	+	+	+	+	+	−	−	−
Gross motor delay	congenital quadriplegic, mostly in wheelchair	walked at 3 years 9 months but now non-ambulatory	could sit, non-ambulatory	sits, non-ambulatory	does not sit, non-ambulatory	walked 4 years 6 months	sits, non-ambulatory	crawled at 3 years; stands and walks only with support	does not crawl or pull to stand, non-ambulatory	no delay	no delay	no delay
Feeding difficulties	+	+	+	+	+	+	+	+	+	−	−	−
Others	FTT, chronic constipation, G-tube feeds	FTT, chronic constipation and diarrhea, G-tube feeds	FTT	FTT	FTT	FTT	FTT, G-tube feeds
Additional neurologic features	congenital quadriplegia, ataxia, spasticity	cerebral palsy, ataxia, spastic quadriplegia	autism spectrum disorder	autism spectrum disorder	autism spectrum disorder	−	−	−	−	−	−	−
Brain imaging	normal	prominent perivascular spaces, hypoplastic corpus callosum, generalized white matter volume loss, gliosis in bilateral parietal lobes	mild fronto-parietal cortical changes	mild fronto-parietal cortical changes, short corpus callosum	mild fronto-parietal cortical changes	normal	cortical and white matter atrophy	mild dilatation of lateral ventricles mainly occipital horns, deep interhemispheric fissure/hypoplastic corpus callosum	normal	normal	normal	normal
Physical Features
CHD	NA	normal echo	PS, ASD	normal echo	PS, ASD, VSD	NA	VSD	NA	TOF, ASD	NA	NA	NA
Other congenital malformations	sacral dimple	spina bifida occulta, cryptorchidism	−	cryptorchidism	−	cryptorchidism	sacral dimple cryptorchidism	−	−	−	−	−
Head/Neck	displaced posterior hair whorl	brachycephaly, sparse hair	short neck, sloping shoulders	short neck, sloping shoulders	short neck, sloping shoulders	−	−	flat occiput, sparse hair	flat occiput	wide forehead, narrow long asymmetric face	wide forehead, narrow long face	narrow long face
Eyes	arched eyebrows, long eyelashes, long palpebral fissures	arched eyebrows, long down-slanting palpebral fissures, ptosis	long palpebral fissures	long palpebral fissures	long palpebral fissures	long palpebral fissures	−	arched eyebrows, deep-set eyes, long eyelashes	deep-set eyes, long eyelashes	down-slanting palpebral fissures	−	−
Nose	long nose, hypoplastic alae, high nasal bridge, long philtrum	prominent nasal bridge, short columella, small alae, smooth long philtrum	broad root and prominent nasal bridge, smooth long philtrum	broad root and prominent nasal bridge, smooth long philtrum	broad root and prominent nasal bridge, smooth long philtrum	−	−	slightly long philtrum	slightly long philtrum	tubular nose	−	−
Mouth/Chin	high arched palate, cupid bow, dental crowding	thin upper lip, downturned mouth corners, high arched palate, mild retrognathia	very thin upper lip, retrognathia	very thin upper lip, retrognathia	very thin upper lip, retrognathia	−	−	thin upper lip	thin upper lip	high arched palate, dental malocclusion, narrow chin	high arched palate, narrow chin	high arched palate
Ears	−	posteriorly rotated ears, bilateral pits	large protruding low-set ears	large protruding low-set ears	large protruding low-set ears	large ears	large ears	large ears	large ears	prominent, dysplastic ears	−	−
Scoliosis	+	+	+	−	−	−	+	+	−	−	−	−
Extremities	broad thumbs, tapered fingers, long first toes, joint contractures, brachydactyly of other toes, hallux valgus	broad thumbs, bulbous finger tips, forearm asymmetry, feet turned outward, joint contractures overriding toes, planovalgus	broad thumbs, clubbed fingers, clubfoot	broad thumbs, hyperextensibility of interphalangeal joints, overriding toes	broad thumbs, hyperextensibility of interphalangeal joints, overriding toes	broad thumbs and first toes, fetal pads	−	bilateral toe syndactyly	bilateral toe syndactyly	arachnodactyly	hyperextensiblity of elbows	arachnodactyly, hyperextensibility of elbows

Abbreviations are as follows: IUGR, intrauterine growth restriction; OFC, occipitofrontal circumference; NA, not available; CHD, congenital heart disease; PS, pulmonic stenosis; VSD, ventricular septal defect; ASD, atrioseptal defect; TOF, tetralogy of Fallot; FTT, failure to thrive. For weight and height, data were obtained from last examination, unless otherwise noted. Z-scores were calculated using the CDC charts for children ages 2–20. For head circumference, z-score was calculated based on published data.³⁸