Table 1.

Clinical features and variants found in the nine individuals of the cohort

Sex	Individual 1	Individual 2	Individual 3a	Individual 4a	Individual 5 (Guo et al., 2019)57	Individual 6	Individual 7	Individual 8	Individual 9	Individual 10
	Male	Male	Female	Female	Male	Male	Female	Male	Male	Male
Age at last examination	11 years	3 years 3 months	12 years 1 month	11 years 1 month	19 years	10 years	13 years	10 years	8 years	43 years
Birth measurements
Weight in g (centile)	3,780 (83rd)	N/Ab	2,950 (14th)	3,720 (87th)	N/A	N/A	3,000 (2–9th)	4,470 (>97th)	4,100 (90th)	N/A
Length in cm (centile)	53 (95th)	N/A	50 (55th)	52 (94th)	N/A	N/A	54 (50–75th)	57 (>97th)	51 (75th)	N/A
OFCc in cm (centile)	39 (99th)	N/A	34.5 (52nd)	37 (98th)	N/A	N/A	N/A	N/A	36.5 (75th)	N/A
Developmental features
Age at sitting (months)	18	delayed	12	7	N/A	N/A	N/A	7	9	12
Age at walking (months)	23	delayed	13	14	N/A	17	11	30	16	17
Age at first words (months)	15	delayed	24	12	N/A	24	14	36	36	15
Developmental delay	+	+	+	+	–	+	+	+	+	+
Intellectual disability degree (IQ)d	mild to moderate	N/A	mild	mild (IQ 57)	IQ 96	no IDe	borderline (IQ 74)	IQ 109	mild to moderate	mild
ASDf	+	N/A	+	–	+	–	–	+	–	–
ADHDg	+	N/A	+	–	suspected	–	+	–	–	–
Neurological features
Hypotonia	+	N/A	+	+	–	–	–	+	–	–
Stereotypies	+	N/A	–	–	–	–	N/A	+	–	–
Epilepsy	–	N/A	–	–	–	–	+	+	–	–
Sleep disturbance	+	N/A	+	+	–	+	+	–	–	–
Brain imaging	Normal	N/A	N/A	N/A	N/A	nodular heterotopia	normal	normal	Normal	N/A
Facial dysmorphism	–	+h	–	+	–	+	+	+	+	+
Additional features
Macrocephaly	Congenital	N/A	Postnatal (93rd centile)	+	N/A	–	N/A	N/A	+ (97th centile)	–
Overweight	–	N/A	+ (99th centile)	+	+	–	–	–	–	+
Joint hypermobility	+	N/A	+	–	–	+	N/A	+	–	–
Others	Hyperopia, temporary regression, megadolichocolon	Learning disabilities	Hyperkinetic disorder, small hands and feet	Small hands and feet	Poor adaptive skills Learning disabilities	Migraine,dermatological issues, genital abnormalities, borderline short stature, advance bone age, clinodactyly	Delayed puberty	Dermatological issues, scoliosis	Learning disabilities	2 Neuroendocrine pancreatic tumors at 43 years
ADGRL1 variant DNA change GRCh37/hg19 GenBank: NC_000019.9 (chr19)	g.14267505A>G	g.14263628G>A	g.14273794C>T	g.14273 794C>T	g.14294389C>T	g.14263409A>G	g.142633 73G>A	g.14270002dup	g.14263332G>A	g.14273591T>C
cDNA change GenBank: NM_001008701.2	c.3013T>C	c.3406C>T	c.834G>A	c.834G>A	c.26G>A	c.3455T>C	c.3491C>T	c.2064dup	c.3532C>T	c.1037A>G
Amino acid chance	p.Trp1005Arg	p.Arg1136∗	p.Trp278∗	p.Trp278∗	p.Trp9∗	p.Met1152Thr	p.Ser1164Phe	p.Glu689Argfs∗113	p.Arg1178∗	p.Tyr346Cys
Inheritance	de novo	de novo	paternally inherited	paternally inherited	de novo	de novo	de novo	de novo	de novo	Paternally inherited
Additional findings	–	9p13.3 deletion	–	–	–	5q14.3 deletion	–	–	6p12.3 duplication	TAOK1
Variant GRCh37/hg19	–	(34655686–34662203)x1	–	–	–	(83112653–85261932)x1	–	–	(47075799–48930453)x3	c.564G>A (GenBank: NM_020791.1)
Amino acid change	–	–	–	–	–	–	–	–	–	p.Trp188∗
OMIM gene phenotypes	–	IL11RA Craniosynostosis and dental anomalies AR,i MIM: 614188	–	–	–	–	–	–	CD2AP Glomerulosclerosis, focal segmental 3, MIM: 607832	Developmental delay with or without intellectual impairment or behavioral abnormalities AD,jMIM: 619575
ACMGk classification	–	VUSl	–	–	–	VUS	–	–	VUS	pathogenic
Inheritance	–	unknown	–	–	–	maternally inherited	–	–	maternally inherited	paternally inherited

^aSiblings.

^bNot available.

^cOccipital frontal circumference.

^dIntellectual quotient.

^eIntellectual disability.

^fAutism spectrum disorder.

^gAttention-deficit hyperactivity disorder.

^hProbably not linked to ADGRL1 variant.

ⁱAutosomal recessive.

^jAutosomal dominant.

^kAmerican College of Medical Genetics and Genomics classification.

^lVariant of unknown significance.