A new Ehlers-Danlos syndrome with craniofacial characteristics, multiple congenital contractures, progressive joint and skin laxity, and multisystem fragility-related manifestations.
We previously described two unrelated patients showing characteristic facial and skeletal features, overlapping with the kyphoscoliosis type Ehlers-Danlos syndrome (EDS) but without lysyl hydroxylase deficiency [Kosho et al. (2005) Am J Med Genet Part A 138A:282-287]. After observations of them over time and encounter with four additional unrelated patients, we have concluded that they represent a new clinically recognizable type of EDS with distinct craniofacial characteristics, multiple congenital contractures, progressive joint and skin laxity, and multisystem fragility-related manifestations. The patients exhibited strikingly similar features according to their age: craniofacial, large fontanelle, hypertelorism, short and downslanting palpebral fissures, blue sclerae, short nose with hypoplastic columella, low-set and rotated ears, high palate, long philtrum, thin vermilion of the upper lip, small mouth, and micro-retrognathia in infancy; slender and asymmetric face with protruding jaw from adolescence; skeletal, congenital contractures of fingers, wrists, and hips, and talipes equinovarus with anomalous insertions of flexor muscles; progressive joint laxity with recurrent dislocations; slender and/or cylindrical fingers and progressive talipes valgus and cavum or planus, with diaphyseal narrowing of phalanges, metacarpals, and metatarsals; pectus deformities; scoliosis or kyphoscoliosis with decreased physiological curvatures of thoracic spines and tall vertebrae; cutaneous, progressive hyperextensibility, bruisability, and fragility with atrophic scars; fine palmar creases in childhood to acrogeria-like prominent wrinkles in adulthood, recurrent subcutaneous infections with fistula formation; cardiovascular, cardiac valve abnormalities, recurrent large subcutaneous hematomas from childhood; gastrointestinal, constipation, diverticula perforation; respiratory, (hemo)pneumothorax; and ophthalmological, strabismus, glaucoma, refractive errors.
Kosho
Tomoki
T
Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan. ktomoki@shinshu-u.ac.jp
Miyake
Noriko
N
Hatamochi
Atsushi
A
Takahashi
Jun
J
Kato
Hiroyuki
H
Miyahara
Teruyoshi
T
Igawa
Yasuhiko
Y
Yasui
Hiroshi
H
Ishida
Tadao
T
Ono
Kurahito
K
Kosuda
Takashi
T
Inoue
Akihiko
A
Kohyama
Mohei
M
Hattori
Tadashi
T
Ohashi
Hirofumi
H
Nishimura
Gen
G
Kawamura
Rie
R
Wakui
Keiko
K
Fukushima
Yoshimitsu
Y
Matsumoto
Naomichi
N
D000015:Abnormalities, Multiple / Q000145:classification / Q000175:diagnosis* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D003286:Contracture / Q000145:classification / Q000175:diagnosis* / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000145:classification / Q000175:diagnosis* / Q000235:genetics; D004535:Ehlers-Danlos Syndrome / Q000145:classification / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D006801:Humans; D007564:Japan; D007596:Joints / Q000002:abnormalities*; D008297:Male; D012868:Skin Abnormalities / Q000145:classification / Q000175:diagnosis / Q000235:genetics; D055815:Young Adult