Table 1

Summary of clinical features observed in individuals with PITX2-related ARS or FOXC1-related ARS in this cohort

Affected system*			PITX2				FOXC1
Affected system*			All N=59	Deletion N=10	PTC N=34	Missense N=15	All N=69	Deletion N=22	PTC N=27	Missense N=20
Eye		Any anterior segment phenotype (%)	100	100	100	100	91	100	85	90
	Anterior segment (%)	Typical ARS anomalies†	93	100	88	100	72	73	77	65
		Corneal opacity†	15	20	15	13	24	23	19	30
		Aniridia†	8	10	6	13	13	23		20
		Primary CG	0	0	0	0	3	5	4	0
	Glaucoma details (%)	Any glaucoma onset (years)	72	57	6	83	66	59	65	73
		dx <2	17	50	11	10	66	70	65	64
		dx 2–10	30	25	22	40	21	10	18	36
		dx 11–20	17	25	11	20	8	0	18	0
		dx 21–60	26	0	56	10	5	20	0	0
		dx age unknown	9	0	0	20	0	0	0	0
		Treatment: drops only	30	25	22	43	21	20	21	20
		Treatment: surgical	70	75	78	57	79	80	79	80
	Dysmorphic facial features (%)		93	100	87	100	78	71	89	73
Syndromic AAnomalies	Additional systemic anomalies (%)		100	100	100	100	69	79	70	58
	Dental	Any dental anomaly	91	100	86	92	42	67	43	14
		Microdontia/hypodontia	91	100	86	92	0	0	0	0
		Enamel hypoplasia/caries	0	0	0	0	30	47	38	0
		Other	7	20	5	0	20	33	14	14
	Umbilical	Any umbilical anomaly	94	100	90	100	11	11	11	11
		RU	42	56	42	42	9	11	11	5
		UH	33	11	39	33	0	0	0	0
		OA	15	33	10	17	0	0	0	0
		Other/unspecified	2	0	0	8	2	0	0	5
	GI	Any GI defect	42	60	41	33	22	26	22	16
		Meckel’s diverticulum	26	30	25	27	0	0	0	0
		Anal anomaly	5	0	9	0	2	5	0	0
		Constipation/IBS	7	20	6	0	6	16	0	5
		Feeding d/o	2	10	0	0	14	11	19	11
	Other features	Congenital heart defect	7	20	6	0	32	32	22	47
		Hearing loss	2	0	3	0	32	58	30	11
		Hypospadias	7	0	13	0	0	0	0	0
		Kidney anomalies	4	0	6	0	8	16	4	5
		Poor growth/FTT	12	10	9	20	17	16	19	16
		Hypotonia/early delays	7	10	6	7	20	16	22	21
		CI	11	30	6	7	9	16	7	5
		Abnormal brain imaging	NED	NED	NED	NED	90	100	80	100
		Any skeletal/joint anomalies	9	10	13	0	25	32	19	26
		Hip anomalies	0	0	0	0	12	11	9	17

*information is included based on availability of relevant clinical data: structural eye anomalies (n=59, PITX2, and n=68, FOXC1); glaucoma, n=32 and 58; dysmorphic facial features, n=37 and 42; systemic anomalies, n=57 and 65; dental anomalies, n=44 and 50; umbilical anomalies, n=52 and 65; hypospadias, n=28 and 24.
†Includes patients with multiple ocular diagnoses; bolded features differ significantly between genes (p<0.05).
ARS, Axenfeld-Rieger syndrome; CG, congenital glaucoma; CI, cognitive impairment; d/o, disorder; dx, diagnosis; FTT, failure to thrive; GI, gastrointestinal; IBS, irritable bowel syndrome; NED, not enough data; OA, omphalocele; PTC, premature termination codon; RU, redundant umbilical skin; UH, umbilical hernia.