Table 1 Clinical features of patients with autosomal recessive LZTR1-associated Noonan syndrome
From: Autosomal recessive Noonan syndrome associated with biallelic LZTR1 variants
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 (90–95th) | 3.9 (75–90th) | 4.5 (>97th) | 4.2 (90–97th) | 3.3 (>97th) | 4.5 (>97th) | 3.32 (50–75th) | 2.3 (AGA) | 4.1 | 3.9 (90th) | 3.46 (50th) | 0.4/0.75 | 2.0 (90th) | 3.5 (AGA) | 3.4 (AGA) | 4 (AGA) | 3.74 (75th–90th) | 2.6 (60th) | 2.55 (AGA) | 3.78 |
BL (cm) | 55.9 (>97th) | 50.8 (50th) | 52.7 (75–90th) | 52 (50–75th) | 43 (10–25th) | 52 (95th) | 50 (50–75th) | 52 (70th) | 48 (2–16th) | 41 (50th) | 50 (AGA) | 51 (AGA) | ||||||||
BOFC (cm) | U | 35.6 (75–90th) | U | 36.5 (90th) | 34.5 (97th) | 37 (98th) | 36 (>90th) | 36 | 34.5 (50th) | 36.2 (50–98th) | 31.5 (90th) | 34 (AGA) | 34 (25th–50th) | 31 (90th) | ||||||
Age at evaluation | 7y6m | 5y6m | 3y8m | 10m | 8y | 3y | 1y | 3y2m | 3y | 3y10m | 2y1m | 7y | 3y4m | 2y10m | 4y9m | 6m | 3y | 3y9m | ||
W (kg) | 22 (25th) | 17.3 (10–25th) | 16.1 (75–90th) | 7.6 (<3rd) | 23.5 (30th) | 12.5 (11th) | 6.0 (<3rd) | 12 (<3rd) | 12 (10th) | 13.5 (25th) | 10.4 (<5th) | 21.4 (10–25th) | 13.8 (<10–25th) | 13 kg (50th) | 14 (3rd) | 3.1 (25th) | (25th–50th) | 12.7 (0.4th–2nd) | ||
L/Ht (cm) | 121 (25th) | 106 (10–25th) | 98 (75–90th) | 67 (<3rd) | 113 (<3rd) | 89 (3rd) | 64 (<3rd) | 85 (5–10th) | 93 (25th) | 89 (3rd) | 78.2 (<5th) | 113 (<3rd) | 88 (<3rd) | 86 (3rd) | 96.5 (<3rd) | (9th–25th) | 93.7 (<3rd) | |||
OFC (cm) | 52 (50–75th) | 52 (50–75th) | 49 (75–90th) | 45.5 (50th) | 53 (57th) | 50 (42nd) | 44 (3rd) | 49.5 (53rd) | 51 (50–75th) | 48.5 (25–50th) | 52 (25–50th) | 51 (50–75th) | 51 (97th) | 48 (3rd–10th) | (50th) | 47 (<3rd) | ||||
Ptosis | + | − | − | − | + | − | + | + | + | − | + | − | + | +/− | ||||||
Short nose or anteverted nares | − | + | − | − | − | − | − | − | − | + | − | + | + | − | ||||||
Depressed or wide bridge | − | − | − | + | − | + | + | + | + | + | − | − | + | + | + | + | − | |||
Widely spaced eyes | − | − | − | − | + | − | + | − | + | + | + | + | − | + | − | |||||
Down-slanted 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 | + | + | − | + | + | + | − | + | + | + | + | + | + | + | + | − | + | + | + | |
Cryptorchidism | NA | − | + | − | − | + | − | + | ||||||||||||
Developmental 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 | See prior | 4/120,894 | NF | 1/120,614 | See prior | See prior | See prior | See prior | See prior | See prior | |||||||
Pat Var frequency in gnomAD | 19/276,182 | 1/245,786 | 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 | 1/30,902 | 11/173,260 | See prior | NF | 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 |
