Table 1.
Clinical and molecular features of patients with mcEDS‐DSE
| Patient | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | Total (n = 8) | mcEDS‐CHST14 (n = 41) |
|---|---|---|---|---|---|---|---|---|---|---|
| Family | 1 | 2 | 3 | 4 | 5 | 6 | ||||
| Publication | Müller et al. (2013) | Syx et al. (2015) | Schirwani et al. (2019) | This study | ||||||
| Patient 1 | Patient 2 | Patient 1 | Patient 2 | Patient 3 | ||||||
| Mutation (cDNA) | c.803C>T/homo | c.799A>G/homo | c.1150_1157del/homo | c.1763A>G/homo | c.960T>A/homo | c.996dupT/homo | ||||
| Amino acid change (amino acid) | p.Ser268Leu | p.Arg267Gly | p.Pro384Trpfs*9 | p.His588Arg | p.Tyr320* | p.Val333Cysfs*4 | ||||
| Age at the publication (years) | 2 | 48 | 39 | 33 | 2 | 19 | 14 | 22 | ||
| Sex | M | F | F | M | M | M | F | M | M 5, F 3 | M 22, F 19 |
| Origin | Indian | Spanish | Portuguese | Pakistani | Turkish | Indian | ||||
| Craniofacial | ||||||||||
| Large fontanel with delayed closure (early childhood) | Yes | NR | NR | NR | Yes | Yes | NR | NR | 3/3 (100%) | 23 |
| Small mouth/micro‐retrognathia (infancy) | NR | Yes | Yes | Yes | NR | NR | NR | NR | 3/3 (100%) | |
| Slender face/protruding jaw (from adolescence) | NR | NR | NR | Yes a | NR | No | No | Yes | 2/4 (50%) | 11 |
| Facial asymmetricity (from adolescence) | NR | NR | NR | No a | NR | Yes | No | No | 1/4 (25%) | 10 |
| Hypertelorism | Yes | Yes | Yes | NR | NR | Yes | Yes | Yes | 6/6 (100%) | 35 |
| Downslanting palpebral fissures | Yes | Yes | Yes | Yes | Yes | Yes | No | Yes | 7/8 (88%) | 34 |
| Short palpebral fissures | NR | Yes | Yes | No a | Yes | Yes | No | No | 4/7 (57%) | |
| Blue sclera | Yes | Yes | Yes | NR | NR | Yes | Yes | Yes | 6/6 (100%) | 25 |
| Midfacial hypoplasia | NR | Yes | Yes | No a | NR | Yes | Yes | Yes | 5/6 (83%) | |
| Short nose with hypoplastic columella | NR | Yes | Yes | No a | No a | No | No | No | 2/7 (29%) | 16 |
| Ear deformity (e.g. low‐set, posterior rotation, prominent) | Yes | Yes | Yes | Yes | Yes | Yes | No | Yes | 7/8 (88%) | 33 |
| Palatal abnormalities (e.g. high, cleft) | Yes | NR | NR | Yes | No | No | Yes | NR | 3/5 (60%) | 25 |
| Long philtrum and/or thin upper lip vermilion | NR | Yes (thin upper lip vermilion) | Yes (both) | No a | Yes (thin upper lip vermilion) a | No | No | No | 3/7 (43%) | 24 |
| Crowded teeth | Yes | NR | NR | Yes | NR | Yes | NR | NR | 3/3 (100%) | |
| Brachycephaly/flat occiput | Yes | NR | NR | No a | Yes | Yes | No | No | 3/6 (50%) | |
| Others | Hypotonic face with wrinkled and saggy eyelids, cheeks, and neck | Prominent forehead | ||||||||
| Skeletal | ||||||||||
| Congenital multiple contractures a | Yes | Yes | Yes | Yes | Yes | Yes | No | Yes | 7/8 (88%) | 41 |
| Adducted thumbs | Yes (bil) | No | No | Yes (bil) | Yes (bil) | Yes (bil) | No | No | 4/8 (50%) | 33 |
| Talipes equinovarus | Yes (bil) | Yes (bil) | Yes (bil) | Yes (bil) | Yes (bil) | No | No | Yes (bil) | 6/8 (75%) | 41 |
| Recurrent/chronic joint dislocations | NR | No | NR | No | No | Yes (shoulder) | No | No | 1/6 (17%) | 20 |
| Pectus deformilties | NR | NR | NR | NR | No | Yes (mild excavatum) | Yes (excavatum, asymmetric) | Yes (excavatum, asymmetric) | 3/4 (75%) | 18 |
| Spinal deformities | NR | No | Yes (mild to moderate scoliosis) | No | No | Yes (mild lumbar scoliosis) | Yes (scoliosis, thoracic kyphoscoliosis) | Yes (scoliosis) | 4/7 (57%) | 22 |
| Finger shape characteristics | Yes (long, tapering) | Yes (long, slender, tapering) | Yes (long, slender, tapering) | Yes (cylingdrical) | Yes (long, slender) | Yes (long, slender) | Yes (long, slender) | Yes (long, slender) | 8/8 (100%) | 35 |
| Progressive foot deformities | NR | Yes (short, broad feet with short toes) | NR | Yes (wide feet with clawed toes) | Yes | Yes (cavus) | Yes (uni. planus) | Yes (hallux valgus, planus, cavus) | 6/6 (100%) | 26 |
| Marfanoid habitus/slender build | NR | NR | NR | No | NR | No | Yes | Yes | 2/4 (50%) | 13 |
| Joint hypermobility | Yes | Yes b | Yes b | No | NR | Yes | No | No | 4/7 (57%) | |
| Osteoporosis | NR | NR | NR | NR | NR | NR | Yes | NR | 1/1 (100%) | |
| Others | Joint pain | Chronic pain, brachydactyly, Madelung deformity | Torticollis | Joint pain | Fractures | |||||
| Skin | ||||||||||
| Hyperextensibility | NR | Yes | Yes | No c | No | Yes | No | No | 3/7 (43%) | 24 |
| Bruisability | NR | Yes | Yes | NR | Yes | No | No | Yes | 4/6 (67%) | 21 |
| Fragility | NR | Yes | Yes | No | No | No | No | No | 2/7 (29%) | 21 |
| Atrophic scars | Yes | NR | NR | NR | No | No | No | Yes | 2/5 (40%) | |
| Hyperalgesia to pressure | NR | NR | NR | NR | NR | NR | NR | NR | 0/0 (0%) | 8 |
| Fine or acrogeria‐like palmar creases | Yes | Yes | Yes | Yes | No | Yes | Yes | Yes | 7/8 (88%) | 28 |
| Recurrent subcutaneous infections | NR | NR | NR | NR | NR | No | No | No | 0/3 (0%) | 8 |
| Fistula formation | NR | NR | NR | NR | NR | No | No | No | 0/3 (0%) | |
| Delayed wound healing | Yes | NR | NR | NR | NR | Yes | No | No | 2/4 (50%) | |
| Umbilical hernia | NR | NR | NR | NR | NR | Yes | No | No | 1/3 (33%) | |
| Others | Transparent, thin | Transparent, thin | Piezogenic pedal papules | |||||||
| Cardiovascular | ||||||||||
| Congenital heart defects | Yes (PFO) | NR | No | No | Yes (ASD) | Yes (ASD, PDA) | No | NR | 3/6 (50%) | 6 |
| Valve abnormalities | No | Yes (MVP, myxomatous valve with ruptureed chordae, severe MR) | No | No | NR | No | No | NR | 1/6 (17%) | 7 |
| Enlargement of ascending aorta | No | No | No | No | NR | No | No | NR | 0/6 (0%) | 2 |
| Large subcutaneous hematoma | NR | Yes | Yes | NR | No | Yes (elbow, arm, forehead, knee, gluteal region) | NR | Yes (calf) | 4/5 (80%) | 20 |
| Respiratory | ||||||||||
| Pneumothorax/Hemopneumothorax | NR | NR | NR | No | No | No | No | No | 0/5 (0%) | 3 |
| Gastrointestinal | ||||||||||
| Constipation | NR | NR | NR | No | No | Yes | No | No | 1/5 (20%) | 9 |
| Diverticula (e.g. perforation, infection) | NR | NR | NR | No | No | No | No | No | 0/5 (0%) | 4 |
| Others | Eventration after gallbladder surgery | |||||||||
| Urological | ||||||||||
| Nephrolithiasis or cystolithiasis | NR | NR | NR | NR | NR | No | NR | NR | 0/1 (0%) | 7 |
| Hydronephrosis | NR | NR | NR | No | NR | Yes (bil) | NR | NR | 1/2 (50%) | 10 |
| Bladder dysfunction | NR | Yes (prolapse after two deliveries) | NR | NR | NR | No | NR | NR | 1/2 (50%) | 2 |
| Recurrent urinary tract infection | NR | NR | NR | NR | NR | No | NR | NR | 0/1 (0%) | 3 |
| Inguinal hernia | Yes (lt) | NR | Yes | Yes (bil) | NR | Yes (lt) | No | No | 4/6 (67%) | 2 |
| Cryptorchidism in male | NR | Yes | No | Yes (bil) | No | 2/4 (50%) | 17 | |||
| Ophthalmological | ||||||||||
| Strabismus | NR | No | No | No | Yes | Yes (esotropia) | No | No | 2/7 (29%) | 14 |
| Glaucoma or elevated intraocular pressure | NR | No | No | No | No | No | No | No | 0/7 (0%) | 8 |
| Refractive error | NR | No | No | Yes (my) | No | Yes (my) | Yes (as) | Yes (my) | 4/7 (57%) | 16 (hy 4, my 12, as 5) |
| Retinal detachment | NR | No | No | NR | NR | No | No | No | 0/5 (0%) | 6 |
| Otological | ||||||||||
| Hearing impairment | NR | NR | NR | NR | NR | Yes (mild, uni, SNHL for high‐pitched sound) | No | No | 1/3 (33%) | 10 |
| Sexual development‐related | ||||||||||
| Hypogonadism | NR | NR | NR | NR | NR | No | NR | No | 0/2 (0%) | |
| Others | Uterine prolapse after two deliveries | |||||||||
| Central nervous system | ||||||||||
| Ventricular abnormalities (enlargement, asymmetry) | No | NR | NR | NR | No | No | NR | NR | 0/3 (0%) | 8 |
| Hypoplasia of septum pellucidum | No | NR | NR | NR | No | No | NR | NR | 0/3 (0%) | |
| Dandy‐Walker variant | No | NR | NR | NR | No | No | NR | NR | 0/3 (0%) | |
| Muscular system | ||||||||||
| Hypotonia | NR | Yes | Yes | NR | NR | Yes | NR | NR | 3/3 (100%) | 14 |
| Muscle weakness | Yes | Yes | NR | NR | NR | Yes | No | No | 3/5 (60%) | |
| Development | ||||||||||
| Motor developmental delay | Yes | NR | NR | NR | Yes | Yes | No | NR | 3/4 (75%) | 23 |
| Intellectual disabilities | No | NR | NR | No | NR | No | No | Yes | 1/5 (20%) | 4 |
Abbreviations: as, astigmatism; ASD, atrial septal defect; bil, bilateral; F, female; hy, hyperopia; lt, left; M, male; MR, mitral valve regurgitation; MVP, mitral valve prolapse; my, myopia; No, absent; NR, not recorded; PDA, patent ductus arteriosus; PFO, persistent foramen ovale; SNHL, sensorineural hearing loss; uni, unilateral; Yes, present.
a
Judged from images in the relevant report.
b
In younger ages but not in adulthood.
c
Only at the elbows.