Page 249 - The Netter Collection of Medical Illustrations - Integumentary System_ Volume 4 ( PDFDrive )

Plate 9-8 Genodermatoses and Syndromes

EHLERS-DANLOS SYNDROME Laparotomy
scar from
previous
Ehlers-Danlos syndrome is a heterogeneous disease GI rupture
of defective connective tissue production. There are
many subtypes, most caused by defects in collagen
formation or in the posttranslational modification of
collagen. This grouping of diseases has been confusing
because of the variable nature of the subtypes and the
lack of a universally adopted classification system.
Under the most recent system, there are 7 distinct
subtypes; under the historical classification, there were
11 types. The new classification system has not been Bruisability
universally adopted, which contributes to the confu-
sion. As the genetic defects behind each subtype are Hyperextensibility
determined, researchers and clinicians will gain a better Parchment-like scars on forehead, of thumb and fingers
understanding of the syndrome. hyperelasticity of auricles
Clinical Findings: Ehlers-Danlos syndrome is a
grouping of connective tissue diseases. Each subtype is
distinct and has a unique underlying genetic defect. Cutaneous
Taken as a whole, the syndrome is estimated to occur nodules
in approximately 1 of every 400,000 persons. Because Hyperextensibility on shins
of the variation in phenotypic expression, the syndrome Exaggerated of elbows
is likely underreported. Most cases are termed classic passive
Ehlers-Danlos syndrome (formerly designated types I dorsiflexion
and II). The onset of signs and symptoms occurs in of ankles
early childhood and can even be manifested at birth.
Each subtype has a different mode of inheritance. Most
are inherited in an autosomal dominant manner, with Genu recurvatum
autosomal recessive inheritance the next most prolific
mode of transmission. X-linked inheritance has been
described. Ehlers-Danlos syndrome affects males and
females equally.
Cutaneous findings are seen in most subtypes of the Hyperelasticity
syndrome. The skin when stretched is hyperextensible, of skin
but it recoils to its resting position promptly and
entirely after being released. Easy bruisability and
excessive scarring are noticed soon after the child Type Inheritance Gene defect (protein)
begins to crawl. The scarring has a characteristic “fish
mouth” appearance, in that the normally thin linear
scars stretch abnormally and leave a profoundly wider Classic AD, AR COL5A1, COL5A2 (collagen V)
scar than would have been predicted. The scar tissue is
extremely thinned and can appear translucent. The Hypermobility AD Unknown, TNXB (tenascin XB) in a small subset
underlying vasculature can be seen prominently through
the atrophic skin, further worsening the appearance of Vascular AD, AR COL3A1 (collagen III)
the scar tissue. Molluscoid pseudotumors and calcified
subcutaneous nodules (spheroids) occur along regions
of repetitive trauma. Epicanthic folds and elastosis per- Kyphoscoliosis AR PLOD1 (lysyl hydroxylase)
forans serpiginosa are two cutaneous findings that can
be seen in cases of Ehlers-Danlos syndrome. Rare Arthrochalasis AD COL1A1, COL1A2 (collagen I)
occurrences of blue sclerae have been reported.
The major morbidity and mortality in Ehlers-Danlos Dermatosparaxis AR ADAMTS2 (procollagen In-propeptidase)
syndrome is seen in the vascular subtype (type IV).
Vascular-type Ehlers-Danlos is subdivided into three Other AR, AD, X FN1 (fibronectin), and some unknown
similar variants and is caused by a defect in the COL3A1
gene. The skin in this subtype is not hyperextensible but AD, autosomal dominant; AR, autosomal recessive; X, X-linked
is rather translucent. Joint laxity is minimally present or
not at all. Individuals with this subtype are more prone
than others with Ehlers-Danlos syndrome to arterial
aneurysms and rupture leading to death. Both large and
medium-sized vessels are involved. The wall of the no functional type III collagen. Because type III colla- Treatment: Patients with Ehlers-Danlos syndrome
colon is easily ruptured, and abdominal pain in these gen is a critical component of the walls of the vascula- need to be under the supervision of a pediatrician who
patients can be an impending sign of colonic rupture. ture and colon, these structures are weakened and are understands the disease. Referral to tertiary care centers
Pathogenesis: Most forms of Ehlers-Danlos syn- prone to distention and breakage. Classic Ehlers- is an appropriate course of action. Patients need to
drome are caused directly by a genetic defect in colla- Danlos syndrome is caused by defects in the COL5A1 avoid unnecessary trauma. They should refrain from
gen synthesis or indirectly by a defect in posttranslational and COL5A2 genes that lead to defective type V col- contact sports. The orthopedic complications can be
modification of collagen. These defects lead to an lagen. Defects in the enzymes lysyl hydroxylase and treated by an experienced orthopedic surgeon. Patients
abnormal amount as well as abnormal functioning of procollagen peptidase, which are responsible for post- with vascular-type Ehlers-Danlos syndrome need to be
the underlying collagen and the properties it imparts to translational modifications of collagen, are present, monitored routinely by a cardiologist and a cardiotho-
the connective tissue. The vascular subtype is caused by respectively, in the kyphoscoliosis and dermatosparaxis racic surgeon. This subtype is the most difficult to
a defect in the COL3A1 gene that leads to minimal or subtypes of Ehlers-Danlos syndrome. manage because of its unpredictable nature.

THE NETTER COLLECTION OF MEDICAL ILLUSTRATIONS 235