. Author manuscript; available in PMC: 2018 Nov 22.

Published in final edited form as: Genet Med. 2018 Feb 22;20(10):1175–1185. doi: 10.1038/gim.2017.249

Table 1. Clinical Features of Patients with Autosomal Recessive LZTR1-Associated Noonan syndrome.

	Family 1 II-1	Family 1 II-2	Family 1 II-3	Family 1 II-4	Family 2 II-4	Family 2 II-5	Family 3 II-1	Family 3 II-4	Family 4 II-1	Family 4 II-2	Family 5 II-4	Family 5 II-1/2	Family 6 II-6	Family 7 II-1	Family 8 II-11	Family 9 II-2	Family 10 II-3	Family 11 II-6	Family 12 V-1	Family 12 V-4
Sex	F	F	F	M	M	M	F	M	M	M	F	F	F	M	M	F	F	M	F	F
Prenatal hydrops, nuchal transl, or cardiac findings	-	+	-	+	+	+	+	+		+	+	+	-	+			+	+	-	-
BW (kg)	4.1 (90-95^th)	3.9 (75-90^th)	4.5 (>97^th)	4.2 (90-97^th)	3.3 (>97^th)	4.5 (>97^th)	3.32 (50-75^th)	2.3 (AGA)	4.1	3.9 (90^th)	3.46 (50^th)	0.4/0.75	2.0 (90^th)	3.5 (AGA)	3.4 (AGA)	4 (AGA)	3.74 (75^th-90^th)	2.6 (60^th)	2.55 (AGA)	3.78
BL (cm)	55.9 (>97^th)	50.8 (50^th)	52.7 (75-90^th)	52 (50-75^th)	43 (10-25^th)	52 (95^th)	50 (50-75^th)			52 (70^th)	48 (2-16^th)		41 (50^th)	50 (AGA)			51 (AGA)
BOFC (cm)	U	35.6 (75-90^th)	U	36.5 (90^th)	34.5 (97^th)	37 (98^th)	36 (>90^th)		36	34.5 (50^th)	36.2 (50-98^th)		31.5 (90^th)	34 (AGA)			34 (25^th-50^th)	31 (90^th)
Age at evaluation	7y6m	5y6m	3y8m	10m	8y	3y	1y	3y2m	3y		3y10m		2y1m	7y	3y4m	2y10m	4y9m	6m	3y	3y9m
W (kg)	22 (25^th)	17.3 (10-25^th)	16.1 (75-90^th)	7.6 (<3^rd)	23.5 (30^th)	12.5 (11^th)	6.0 (<3^rd)	12 (<3^rd)	12 (10^th)		13.5 (25^th)		10.4 (<5^th)	21.4 (10-25^th)	13.8 (<10-25^th)	13 kg (50^th)	14 (3^rd)	3.1 (25^th)	(25^th-50^th)	12.7 (0.4^th-2^nd)
L/Ht (cm)	121 (25^th)	106 (10-25^th)	98 (75-90^th)	67 (<3^rd)	113 (<3^rd)	89 (3^rd)	64 (<3^rd)	85 (5-10^th)	93 (25^th)		89 (3^rd)		78.2 (<5^th)	113 (<3^rd)	88 (<3^rd)	86 (3^rd)	96.5 (<3^rd)		(9^th-25^th)	93.7 (<3^rd)
OFC (cm)	52 (50-75^th)	52 (50-75^th)	49 (75-90^th)	45.5 (50^th)	53 (57^th)	50 (42^nd)	44 (3^rd)	49.5 (53^rd)	51 (50-75^th)		48.5 (25-50^th)			52 (25-50^th)	51 (50-75^th)	51 (97^th)	48 (3^rd - 10^th)		(50^th)	47 (<3^rd)
Ptosis	+	-	-	-	+	-		+	+		+			-	+		-		+	+/-
Short nose or anteverted nares	-	+	-	-	-	-					-			-	-	+	-	+	+	-
Depressed or wide bridge	-	-	-	+	-	+	+		+		+		+	-	-	+	+	+	+	-
Widely spaced eyes	-	-	-	-	+	-			+		-		+	+	+	+	-		+	-
Downslanted palpebral fissures	-	-	-	-	+	-		+	+		+		+	+	+	+	-	+	+	-
Low-set ears	-	+	-	+	+	-	+	+	+		+			+	+		+	+	+	+
Post angulated ears	+	+	+	+	+	+			+		+			+	+		+	+	+	+
Malformed ears	-	-	+	+	+	+			+		+			-	-		-		-	-
Midface retrusion	+	+	-	-	+	+			-		+/-		+	+/-	-		-		+	+
Micrognathia	+/-	+/-	+/-	+/-	+	+			+		+			-	-		+/-		-	-
Broad/short neck	+	+	+	+	+	+	+		+	+	-	+	+	+	+	+	+	+	-	-
Low posterior hairline	+	+	+	+	+	-	+		+	-	-			+			-		+	+
Wide-spaced nipples/Broad chest	-	-	+	-	+	-	+				+	+	+	+			+	+	+	+
Pectus carinatum or excavatum	+	+	+	-	+	-			+		-			+	-		-	+	+	+
Curly hair	-	+	+	-	-	-			-		+			+	+	-	-		+	-
Cardio-myopathy	-	-	-	-	+	+	+	+	+	+	+			+	+	+	+	+	+	+
CHD or Valvular disease	+	+	-	+	+	+	-	+	+	+	+	+		+	+	+	-	+	+	+
Cryptorchid-ism			NA	-	+	-			-	+				-	+
Dev delay/ID	-	+/-	-	-	+	+			+		-			+	+	+	+		+	+
Paternal variant	c.628C>T p.R210*				c.2178C>A p.Y726*		c.1943-256C>T		c.1687G>C p.E563Q		c.2407-2A>G		c.27delG p.Q10fs	c.361C>G p.H121D	c.508C>T; c.614T>C p.R170W; I205T	c.650A>C, p.E217A	c.2062C>G, p.R688G	c.2325+1G>A	c.2462T>C p.I821T	c.2462T>C p.I821T
Maternal variant	c.2220-17C>A				c.1943-256C>T		c.1943-256C>T		c.1687G>C p.E563Q		c.2090G>A p.R697Q		c.1149+1G>A	c.2264G>A p.R755Q	c.508C>T; c.614T>C p.R170W; I205T	c.650A>C, p.E217A	c.1943-256C>T	c.1943-256C>T	c.2462T>C p.I821T	c.2462T>C p.I821T
Pat Var frequency in ExAC	12/120,308				NF		See prior		NF		NF		1/15,734	NF	2/120,622; NF	NF	NF	NF	NF	See prior
Mat Var frequency in ExAC	NF				1/13,270		See prior		NF		4/120,894		NF	1:120,614	See above	See prior	See prior	See prior	See prior	See prior
Pat Var frequency in gnomAD	13/220,926				NF		See prior		1/245,294		NF		NF	NF	3/245,898; 2/245,670	NF	NF	NF	1/30,936	See prior
Mat Var frequency in gnomAD	NF				NF		See prior		See prior		7/246,118		1/241,846	1/246,052	See prior	See prior	See prior	See prior	See prior	See prior
Pat Var CADD	40				40		Spl		24		24.6		29.8	29.8	34;23.6	23.2	34	Spl	27.3	27.3
Mat Var CADD	Spl				Spl		Spl		24		35		23.7	35	34;23.6	23.2	Spl	Spl	27.3	27.3

Note that the twins in Family 5 are here presented as a single occurrence. Insufficient clinical data for individual II-2 in Family 7 was available to populate this table. Nuchal transl indicates nuchal translucency. V1 and V2 are the two genetic variants in the affected patients. BW, BL, and BOFC are birth weight, birth length, and birth occipitofrontal circumference. In the age entries, y and m are years and months, respectively, W, L/Ht, and OFC are weight, length/height, and occipitofrontal circumference. Post angulated ears is posterior angulation of the ears. CHD is congenital heart defect. ID is intellectual disability. + indicates feature present, - indicates feature absent, +/- indicates feature ambiguous or mild, NA is not applicable. NF indicates that the variant was not present in the database. Pat Var is the variant in that sibship that was inherited from the father. Mat Var is the variant in that sibship that was inherited from the mother. CADD is the combined annotation dependent deletion Phred-like score. CADD scores are not relevant to frameshift or non-canonical splice variants, and therefore “Fs” or “Spl” are specified there instead of numbers, when applicable.