TABLE II.
Supporting and Misleading Diagnostic Features
| Pt No. | Clinical/molecular diagnosis | % correct response | Number of clinicians commenting | Reported supporting features (n) | Reported misleading features |
|---|---|---|---|---|---|
| 1 | Classic CdLS, NIPBL, p.R1335LfsX1357 | 98 | 35 | Microcephaly (1), hirsutism (1), ears (3), synophrys (12), arched brows (14)a, penciled brows (1), bushy/long lashes (7), high set/short nose (10)a, upturned nose (6), long philtrum (15)a, prominent upper lip (4), thin upper lip (11), downturned mouth (6), micrognathia (8)a, gestalt (5), limbs (2), nevus flameus (1) | Severe micrognathia (1), Rubinstein–Taybi? (1) |
| 2 | Not CdLS, 9q del | 60 | 40 | High hairline/square forehead (4), thin/sparse hair (5), small ears (1), upslanted palpebral fissures (1), hypertelorism (2), short nose (4), flat midface (1), normal/short philtrum (6), broad/prominent mandible/prognathism (10)a, thick/full lips (18)a, gestalt/overall facies (2), coarse facies (5), Ka- buki? (1), Pallister–Killian? (1), Coffin–Siris? (1), 3q11del? (1), MPS? (1), Trisomy 21-like (4) | Thickened ear helices (1), synophrys (2)a, arched brows (4)a, long/up- turned lashes (5), short nose (3), upturned/anteverted nose (2), prominent maxilla (1), thin upper lip (1), downturned mouth (2), African-American difficult (2)a |
| 3 | Classic CdLS, NIPBL p.D817GfsX819 | 100 | 26 | Micro/brachycephaly/round face (5), hirsutism (4), ears (2), synophrys (11)a, arched brows (16)a, penciled brows (7), long lashes (5), high set/short nose (11)a, upturned/anteverted nose (10)a, long philtrum (14)a, thin upper lip (17)a, downturned mouth (5), micrognathia (6), gestalt/overall facies (2), limbs (2) | |
| 4 | Not CdLS, fetal alcohol syndrome | 97 | 30 | No micro/brachycephaly (2), frontal bossing/tall forehead (10)a, low set ears (1), sparse hair/brows (2), full eyebrows (1), no synophrys (2), short palpebral fissures (1), broad nose (5)a, tented upper lip (2), short philtrum (3), prominent philtral groove (2), full lips (5)a, no facial gestalt (7), FAS? (1), chromosomal anomaly? (1), Sotos? (1), Simpson–Golabi–Behmel? (1) | Upturned nose (1), downturned mouth (2)a |
| 5 | Mild CdLS, SMC1A, p.R790Q | 57 | 30 | Brachycephaly (1), hirsutism (1), ears (1), syn- ophrys (7)a, full/prominent brows (4), long lashes (5), eye/nose junction (1), high set/short nose (7)a, triangular nose (2), upturned/anteverted nose (2), long philtrum (11)a, thin upper lip (8)a, micrognathia (1), partial gestalt/facies (1) | No brachycephaly (1), large/normal ears (1)b, flat/straight brows (15)b, full/bushy brows (2)b, prominent/normal nasal bridge (8)b, broad nose (2)b, no anteverted nose (1), full cheeks (1), thin upper and lower lips (1), 1p36del? (4)a, dup 3? (1), 9q34del? (1) |
| 6 | Classic CdLS, NIPBL, p.R1789G | 80 | 34 | Ears/low set ears (4), synophrys (2), brows (8)a, arched brows (1), penciled brows (1), long lashes (17), ptosis (1), high set/short nose (15)a, upturned/anteverted nose (3), long philtrum (11)a, thin upper lip (1), downturned mouth (6), chin (1), gestalt/overall facies (1) | No synophrys (1), flat/wrong/bushy brows (6)a, full nose (1), full lips (8)a, wrong gestalt (1), African descent difficult (6)a, BPES? (1) |
| 7 | Classic CdLS, NIPBL, c.3048delATTA | 94 | 29 | Brachycephaly (3), synophrys (10)a, arched/penciled brows (9)a, long lashes (6), high set/short nose (7), upturned/anteverted nose (4), long philtrum (11)a, thin upper lip (9), downturned mouth (5), micro/retrognathia (3), gestalt/overall facies (2), small hand (2), nevus flameus (1) | Severe brachycephaly (1), high hairline (1), wrong ears/thick helices (1), flat midface (1), wrong nose (1), chin too large (1), atypical/mild gestalt (2), Down syndrome? (4), chromosomal anomaly? (1), Smith–Magenis? (1) |
| 8 | Classic CdLS, NIPBL, c.3048delATTA | 100 | 31 | Micro/brachycephaly/round face (1), synophrys (10), arched/penciled brows (13)a, long lashes (4), high set/short nose (5)a, upturned/anteverted nose (6), long philtrum (13)a, thin/prominent upper lip (14)a, downturned mouth (7)a, micro/retrognathia (4), gestalt/overall facies (3) | Less brachycephaly (1), less brow arch (3), fine/less coarse brow (2), obese/healthier (2), blond (1), 9q34del? (1) |
| 9 | Mild CdLS, NIPBL, p.Q1973P | 31 | 30 | Round face (1), ears (1), synophrys (3), arched/ penciled brows (8)a, long lashes (5)a, nose (1), thin upper lip (6), mouth (2) | Large head (2), normal ears (1), normal brows (3), flat/straight brows (4)a, no midface hypoplasia (1), normal nose (4)a, no nose upturn (1), normal philtrum (6), no downturned mouth (1), normal lips (5), prominent chin (1), overall gestalt/nondysmorphic (7)a, 1p36? (1), 22q11 del? (1) |
| 10 | Not CdLS, floating harbor | 97 | 27 | No brachycephaly (1), no synophrys (1), upslanted eyes (1), no midface hypoplasia (2), high nasal bridge/large nose (4), downturned nasal tip/wrong nose (7)a, short philtrum (1), prominent chin (1), smiling/too happy (2), nondysmorphic (1), overall gestalt (3), “pixie” face, Rubinstein–Taybi? (6)a, Kabuki if flatter nose (1) | Thin lips (2), micrognathia (1) |
| 11 | Mild CdLS, SMC1A, p.R496H | 54 | 30 | Round face (1), eyes (2), synophrys (2), arched brows (2)a, brows (3)a, heavy/full brows (3)a, nose (6)a, nasal root (1), high set/short nose (5)a, upturned/anteverted nose (2), long philtrum (5)a, thin upper lip (4), mouth (3), downturned mouth (1) | Face shape/no brachycephaly (2), eyes (1), no synophrys (1), thick brows (2)b, no midface hypoplasia/ high nasal bridge (2), nose, odd/ VCFS-like/pinched/not triangular (5)b, mouth (1), normal philtrum (5), lips too thick (1), no retrognathia (2), hair obscures (2), normal/nondysmorphic (3), dup 3q? (1), 22q11 del? (1) |
| 12 | Mild CdLS, SMC1A, p.R196H | 82 | 30 | Low ears (1), eyes (2), synophrys (4), brows (2), arched brows (6)a, penciled brows (1)a, long lashes (1), nose (4)a, upturned/anteverted nose (1), philtrum (6)a, thin upper lip (8), mouth (4), downturned mouth (2), gestalt/overall facies (2), skeletal films? (1) | Broad face (1), normal ears (1), long palpebral fissures (1), brows broad (2)/different (2)/interrupted (1)b, nose broad (1)/not high set (1)b, short philtrum (1), FAS? (2)a, chromosomal anomaly? (1), Kabuki? (1) |
| 13 | Not CdLS, fetal alcohol syndrome | 97 | 34 | Head shape (3), no brachycephaly/large/long face (3), prominent forehead (2), no lowset ears (1), brows (6), no synophrys (5), eyes (1), periorbital fullness (1), short palpebral fissures (2), hypertelorism (1), nose (2)/broad (1)/high bridge (2), short philtrum (1), full upper lip (1), no CdLS gestalt (4)/nondysmorphic (2), FAS? (13), fragile X? (1), 22q11 del? (2), Sotos? (1)/Williams? (1)/ Kabuki? (1) | Arched brow (2), nose (2), depressed nasal bridge (1), midface (2), mouth (3)a, thin upper lip (3)a |
| 14 | Not CdLS, 46,XY, der(3)t(3;12) (p25.3;p13.3) | 48 | 36 | Head (1), no brachycephaly (1), long face (2), high hairline, forehead (2), thin hair (1), increased facial movement (1)a, hypertelorism (1), brows (4), thin medially (2)a, nose (4), mouth (5), wide (4)a, chin (1), prognathism (1), no gestalt (1), too atypical for CdLS (2), Kabuki-like? (6), Angelman-like (2), Borjeson–Forssman–Lehmann? (1), FAS? (1), Coffin–Siris? (1) | Synophrys (4), arched brows (9)a, lashes (3), nasal bridge depressed (1), short (3), anteverted nares (7)a, thin lips (6), philtrum (1), long (1), CdLS gestalt (4) |
| 15 | Mild CdLS, SMC1A p.V58_R62del | 52 | 27 | Brachycephaly (1), round face (1), profile (3), posterior hairline (1), lowset ears (1), synophrys (4), arched brows (1), penciled brows (1), flat midface (1), low nasal root (1), nose (2), high set (1), short nose (2)a, upturned, anteverted nose (1)a, long philtrum (1), lip (2), prominent upper lip (5), thin lips (4)a, mouth (2), downturned (2)a, micro, retrognathia (1), gestalt (1) | No synophrys seen (2), brows (1), less arched (1), thin medially (2), prominent (1)b, eyes (2), nose (1), mid nose (1), tip nose (1)b, short philtrum (1), full cheeks (1), smile (1), too normal (1), no CdLS gestalt (1), Kabuki? (1) |
| 16 | Not CdLS, Aarskog syndrome | 98 | 23 | Large head (1), forehead (1), ear (1), eyes (2), hooded (1), no synophrys (1), normal brows (5), lashes (1), narrow palpebral fissures (1), nose (2), broad (2), no flat midface (1), short philtrum (3), mouth (2), cheeks full (1), normal facial movement (1), normal, no CdLS gestalt (11), Noonan? (1), Williams? (1), 22q11del? (1) | Thin upper lip (1), feeding issues (2) |
| 17 | Classic CdLS, NIPBL c.6407insA | 100 | 27 | Round face (3), low frontal hairline (1), hirsutism (1), ears (1), brows (11), arched (3), penciled (1)a, synophrys (9)a, eyes (1), long lashes (1), nose (7), high set or short (2), anteverted (2)a, philtrum (4), long (6), smooth (1), prominent (1)a, mouth (2), downturned (6)a, lips (5), thin upper lip (8)a, chin (2), micro, retrognathia (1), gestalt, overall facies (6) | Nares not anteverted (1), less coarse (1) |
| 18 | Not CdLS, Dubowitz syndrome | 97 | 30 | Forehead (2), prominent (1), tall (2), no synophrys (1), brows (5), thick/bushy (3), no arch (1)a, eyes (3), downslanted (1), epicanthal folds (1), blepharophimosis (4), nose (2), broad (1), long (2), prominent root (1), no upturn (1), short philtrum (2), full lips (2), normal mouth (3), no CdLS gestalt (4), FAS? (8), FG? (1), 22q11del? (1), Mowat- –Wilson? (1) | CdLS ears (1) |
| 19 | Not CdLS, Rubinstein–Taybi syndrome | 92 | 33 | No round face (1), eyebrows not seen (4), brows (2), small ears (1), nose (7), long (4), beaked (3), prominent (3), long columella (1), short philtrum (3), mouth not downturned (1), not CdLS (1), no CdLS gestalt (2), Rubinstein–Taybi? (12)a, 22q11del? (2), Alagille? (1), postsurgical Treacher-Collins? (1), floating harbor? (1) | |
| 20 | Mild CdLS, NIPBL, p.R2298H | 89 | 27 | Round face (1), eyes (2), brows (7), synophrys (4), arched (6), thin, penciled (4), high (1)a, lashes (1), nose (9), high set (1), short (2), upturned/anteverted (5)a, mouth (4), small (2), downturned (2), philtrum (5), long (8), smooth (1)a, lips (2), thin upper (9)a, micro/retrognathia (2), gestalt/overall facies (2) | Ears not quite right (1), full cheeks (2)a, nose atypical (2) |
| 21 | Mild CdLS, SMC1A, p.F133V | 82 | 32 | Face shape (1), lower face (2), eyes (2), brows (1), arched (1), synophrys (2), nose (2), short (1), anteverted (1), tip (1)a, mouth (6), downturned (7)a, philtrum (1), long (2), lips (1), prominent upper (4), thin upper (4)a, mouth (6), downturned (7)a, micro/retrognathia (1), gestalt/overall facies (1) | Normal ears (1), eyes (1), heavy/ bushy brows (2)b, low brows (1)b, nose, normal (1), long (1)b, no midface hypoplasia (1)b, blond difficult (1), Alagille? (1), 9q34? (1) |
| 22 | Mild CdLS, Familal Case, cannot exclude 5p13 | 23 | 24 | Lashes (1), brows (1), arched (1), upslanted eyes (1), nose (1), anteverted (1), gestalt/overall facies (2) | Uplifted ear lobes (1), brows (2), straight (3), nose (3), pointed (1), long root (2), phltrum (1), short (3), mouth (3), normal (1), chin (1), prominent (2), defined (1), normal facial movement/expression (2), no hirsutism (1), normal gestalt (3), Angelman? (1), RTS? (1) |
| 23 | Mild CdLS, NIPBL, p.Q1338R | 45 | 27 | Round face (1), brows (5), arched (3), synophrys (5)a, long lashes (2), nose (1), philtrum (1), lips, thin upper (4)a, gestalt/overall facies (1) | Eyes (1), hypertelorism (1), brows (2), thick (1), low (1), flat (1), nose (3), long (1), no anteversion (1), prominent root (2), small alae (2), low columella (2)a, philtrum, short (5), mouth, no downturned corners (1), no micrognathia (1), no hirsutism (1), normal gestalt (3), Alagille? (2), 22q11del? (1), floating harbor? (1) |
| 24 | Not CdLS, Kabuki | 97 | 24 | Head, big (1), no brachycephaly (1), ear (2), brow (7), no arch (1), bushy (2), lashes, sparse (1), eyes, upslanted (1), hypertelorism (1), hooded (1), epicanthal folds (1), everted lower lids (1)a, nose (3), round (1), bulbous (2), downturned (2)a, philtrum (1), flat (1), mouth (2), small (1), lips (1), full upper (4)a, fine features (1), overall gestalt not CdLS (3), Kabuki? (1), 22q11del? (2), Dubowitz? (1) | |
| 25 | Mild CdLS, NIPBL, p.D1830V | 70 | 28 | Brachycephaly (1), round face (3), low frontal hairline (1), hirsutism (1), ears (1), eyes (2), brows (10), arched (6), thin/penciled (1), synophrys (1)a, long lashes (2), nose (2), high set/short (1), root (1)a, philtrum (1), long (1), lips (3), thin upper (7)a, chin (1), gestalt/overall facies (2), grimace smile (1)a | Ear (1), nose (2), short philtrum (1), mouth (2), square chin (1), no retrognathia (1), happy/smiling (2)a, no gestalt (2), Cohen syndrome? (1) |
| 26 | Mild CdLS, SMC1A, p.F1122L | 19 | 23 | Brows (4), slight arched (1)a, midface (1), | Brows (2), eyes (1), eye contact (1), nose wrong (6)b, upper lip (1), short philtrum (3), mouth (2), dimples (2), lips (1)a, facial movement/good smile (2), well-defined chin (1), nondysmorphic (10)a, wrong gestalt (3), 22q11del? (2)b |
| 27 | Classic CdLS, NIPBL, p.R2298C | 89 | 23 | Eyes (4), brows (8), arched (2), heavy (2), synophrys (5)a, lashes (1), nose (3), high set (1), sharp (1), mouth (4), downturned (6), lips (2), thin upper (5), micro/retrognathia (1), smile (1), gestalt/overall facies (6) | Thick brows (2)a, nose (1), no anteversion (2)a, short philtrum (6), upper lip (1) |
| 28 | Mild CdLS, NIPBL, p.Q1338R | 46 | 24 | Low ears (1), eyes, palpebral fissures (1), brows (6), arched (2), bushy (1), synophrys (4)a, lashes (1), nose (1), philtrum (1), lips, thin upper (2), gestalt/ overall facies (2) | Ear (1), short palpebral fissures (1), raising brows (1), nose (3), high bridge (1), mouth (2), no downturn (1), short philtrum (2), lower face (1), chin (2), long (1), broad (4), prognathism (3), no micrognathia (1)a, gestalt (1), happy (1), up-turned smile (1)a, FAS? (1) |
| 29 | Classic CdLS, NIPBL, p.S235X | 63 | 25 | Microcephaly (1), head shape (1), thickened ear helices (1), eyes (2), brows (4), arched (1), heavy (1), synophrys (2), lashes (1), midface hypoplasia (2), nasal tip (1), mouth (1), downturned (2), philtrum (1), gestalt/overall facies (1) | No brachycephaly (1), ears (1), thick brows (1)a, nose (1), built-up root (2), broad bridge (2)a, lower face (1), short philtrum (1), broad jaw (1), prognathism (13), no retrognathia (1)a, no thin upper lip (1), coarsening (3)a, no gestalt (1), Coffin–Lowry? (1), Phelan- –McDermod? (1), ATRX? (1)a |
| 30 | Classic CdLS, NIPBL, p.R1895T | 89 | 22 | Eyes (1), brows (8), arched (2), long lashes (1), nose (2), short (1), upturned/anteverted (1), mouth (4), downturned (4)a, philtrum (2), long (1), lips, prominent upper (1), thin upper (2), chin (1), gestalt/overall facies (3), lower face (1)a, grimace- like smile (1)a, small hands (1) | Short philtrum (2), alert (1), no gestalt (1), FAS? (1), cytogenetic abnormality (1) |
| 31 | Classic CdLS, NIPBL c.7825insG | 80 | 26 | Thick hair (1), eyes (2), brows (6), arched (1), synophrys (5)a, lashes (1), nose, high set/short (1), midface hypoplasia (1), mouth (4), down-turned (5)a, philtrum, long (1), lips (1), prominent upper (1), thin upper (1), gestalt/overall facies (5) | Brows, thick (1), wide laterally (1), nose (5), depressed tip (2)a, upper lip (1), lower face (1), chin (2), prognathism (1), Smith–Magenis? (1), Kabuki? (1) |
| 32 | Classic CdLS, NIPBL, p.R1536X | 98 | 23 | Hirsutism (1), eyes (3), downslanted (1), brows (6), arched (2), synophrys (9)a, long lashes (2), nose (3), high set/short (2), anteverted (4)a, mouth (6), downturned (4)a, philtrum (4), long (1), lips (1), prominent upper (1), thin upper (6)a, chin (1), micro/retrognathia (2), square (1), gestalt/overall facies (6), lower face (1) | Prominent nasal bridge (1) |
Features described from top of head to chin and then overall impressions. del, deletion; dup, duplication.
a
Distinguishing feature.
b
Variant feature characteristic in patients with SMC1A mutations.