THE SYNDROME PAGE
Editors: Susan B. Mallory, M.D., and Bernice R. Krafchik, M.B.,
What Syndrome Is This?Jean Graham, M.D.,* and Nancy B. Esterly,
*Department of Dermatology, University of New Mexico,
Albuquerque, New Mexico, and Medical College ofWisconsin,
A male infant was born at 37 weeks gestation to a 30-year-old
gravida 2, para 1, healthy white woman. Therewas no history of
consanguinity. Her first child, by adifferent father, had no
congenital defects. The affectedinfant weighed 1620 g (less than
10th percentile) andmeasured 41.5 cm crown to heel (less than 10th
percen-tile). His Apgar scores were 7 at both 1 minute and
5minutes, and he was in severe respiratory distress. Physi-cal
examination showed extensive areas of shiny, tight,translucent and
erythematous skin which was fragile andtore easily (Figs. 1 and 2).
At other sites the skin wasthickened, fissured, and scaly. There
were no blisters.His head and mandible were small. There was no
hair onthe scalp and the eyebrows were absent. His eyes
werealmond-shaped with an antimongoloid slant. The mouthwas fixed
in an open position and was O-shaped. He hadjoint contractures at
the hips, knees, elbows, wrists, and
ankles. Radiographs showed evidence of fractures of theright
humerus, right radius and ulna, and right tibia. Theribs were thin
and the cranial vault was small with anunderdeveloped mandible. He
attempted to feed, but wasunable to adequately suck or swallow. The
patient died at26 hours of age from respiratory arrest.
Three skin biopsy specimens were obtained shortlyafter birth
from the skin of the shoulder and back (Figs.3 and 4). The
epidermis was hyperkeratotic with broadzones of laminated
orthokeratosis and focal parakerato-sis. The rete pegs were absent,
resulting in a flatteneddermoepidermal junction. The dermis was
thin and thecollagen formed dense bundles oriented parallel to
theepidermis. Appendageal structures were rare, and thosepresent
were immature and distorted. No elastic fiberswere detected by
Movat stain. The subcutaneous tissuewas greatly thickened with
WHAT IS YOUR DIAGNOSIS?
Address correspondence to Nancy B. Esterly, M.D., Pediatric
Derma-tology, Froedert East, 9200 W. Wisconsin Ave., Milwaukee, WI
Figure 1. Characteristic skin changes, contractures, andfacial
Figure 2. Torn skin on the neck and upper chest.
Pediatric Dermatology Vol. 16 No. 2 151153, 1999
Restrictive dermopathy (RD) is an autosomal recessivecongenital
skin disorder typified by abnormally rigidskin, flexion
contractures, and characteristic facialanomalies consisting of
micrognathia, low-set ears, fixedopen mouth, small pinched nose,
and eyes with an anti-mongoloid slant (15). The joint contractures
in theseinfants are thought to arise from decreased fetal move-ment
in utero (known as the fetal akinesia deformationsequence)
secondary to the taut skin (1). The disorder isuniformly fatal.
Before restrictive dermopathy was clearly defined,Leschot et al.
(6), Carmi et al. (7), and Toriello et al. (8)described a total of
five infants with extensive skin ero-sions and contractures, all of
whom were initially diag-nosed as aplasia cutis congenita, an error
subsequentlyrecognized by Toriello (9). In 1985, Lowry et al.
(10)reported on four Mennonite/Hutterite infants with an
un-classified congenital disorder the major clinical manifes-
tations of which were intrauterine growth
retardation,contractures, low-set ears, hypertelorism,
micrognathia,and lethality. It was proposed that these patients
repre-sented a new syndrome distinct from other lethal con-genital
syndromes such as NeuLaxova syndrome,PenaShokeir syndrome, and
aplasia cutis congenita.Witt et al. (1), after evaluating cases of
their own andothers from the literature, named the syndrome
restric-tive dermopathy in 1986.
Infants affected with restrictive dermopathy have re-markably
consistent clinical features, histopathologicfindings, and
radiologic abnormalities. Due to restrictedfetal movement, a
majority of these infants have intra-uterine growth retardation,
joint contractures, and pul-monary hypoplasia (11). The taut, shiny
skin is unique toRD and is described in all cases (15,1215).
Because ofits rigidity, the skin often tears in response to the
stress ofdelivery or neonatal movement.
Skin biopsy specimens show a thickened hyperkera-totic and
hyperplastic epidermis overlying a relativelythin dermis composed
of dense bundles of collagenaligned parallel to the epidermis. The
dermoepidermaljunction is flat, the dermis is thin, and epidermal
append-ages are absent or appear miniaturized and immature(16).
Elastic fibers are extremely small or absent; adiposetissue may be
increased in amount. Electron microscopicstudies have demonstrated
decreased numbers of keratinfilaments in the spinous and granular
layers, as well asstructurally abnormal keratohyalin granules.
Radiologicabnormalities include poorly mineralized cranial
bones,overtubulation of the long bones, hypoplastic clavicleswith
incomplete ossification and slender, ribbonlike ribs(15).
The etiology of RD is unknown. Defects in collagensynthesis have
been identified (17) and abnormalswitched off fibroblast
populations have been de-scribed (13). Verloes et al. (12)
suggested that a regula-tory factor, defective in RD and normally
present in der-moepidermal interactions, might have polytopic
effectsand thus play a role in the defective ossification of
bones,the fragility of the amniotic membrane, and the
Accurate prenatal diagnosis would provide valuableinformation
for families at risk, but, unfortunately, thishas been
unsuccessful. Skin biopsy specimens from af-fected fetuses up to 20
weeks of age have been reportedas normal (18). Ultrasound
examinations performed aslate as 18 weeks have also been
interpreted as normal(19), making these studies ineffective for
diagnosing RDin time for consideration of therapeutic abortion.
De-creased fetal movements and absence of swallowing andbreathing
movements have only been observed late in thepregnancy, at 28 to 29
weeks (2,14). Amniocentesis, as
Figure 3. The epidermis is thickened and the dermoepi-dermal
junction flat. Appendages are sparse and hypo-plastic.
Figure 4. Elastic tissue stain shows absence of
152 Pediatric Dermatology Vol. 16 No. 2 March/April 1999
well, has failed to yield useful information. Geneticcounseling
is essential for families at risk for this auto-somal recessive,
1. Witt DR, Hayden M, Holbrook KA, et al. Restrictive
der-mopathy: a newly recognized autosomal recessive skindysplasia.
Am J Med Genet 1986;24:631648.
2. Mok Q, Curley R, Tolmie JL, et al. Restrictive dermopa-thy: a
report of three cases. Am J Med Genet 1990;27:315319.
3. Hoffmann R, Lohner M, Bohm N, et al. Restrictive der-mopathy:
a lethal congenital skin disorder. Eur J Pediatr1993;152:9598.
4. Van Hoestenberghe M, Legius E, Vandevoorde W, et
al.Restrictive dermopathy with distinct morphological
abnor-malities. Am J Med Genet 1990;36:297300.
5. Welsh KM, Smoller BR, Holbrook KA, et al.
Restrictivedermopathy. Arch Dermatol 1992;128:228231.
6. Leschot NJ, Treffers PE, Becker-Bloemkolk MJ, et al. Se-vere
congenital skin defects in a newborn. Eur J ObstetGynecol
7. Carmi R, Sofer S, Karplus M, et al. Aplasia cutis congenitain
two sibs discordant for pyloric atresia. Am J Med
8. Toriello HV, Higgins JV, Waterman DF. Letter to the edi-tor:
Autosomal-recessive aplasia cutis congenitareportof two affected
sibs. Am J Med Genet 1983;15:153156.
9. Toriello HV. Invited editorial comment on restrictive
der-mopathy and report of another case. Birth Defects
10. Lowry RB, Machin GA, Morgan K, et al. Congenital con-
tractures, edema, hyperkeratosis, and intrauterine
growthretardation: a fatal syndrome in Hutterite and
Mennonitekindreds. Am J Med Genet 1985;22:531533.
11. Moerman PH, Fryns JP, Goddeeris P, et al. Multiple
an-kyloses, facial anomalies, and pulmonary hypoplasia asso-ciated
with severe antenatal spinal muscular atrophy. JPediatr
12. Verloes A, Mulliez N, Laloux F, et al. Restrictive
der-mopathy, a lethal form of arthrogryposis multiplex withskin and
bone dysplasias: three new cases and a review ofthe literature. Am
J Med Genet 1992;43:539547.
13. Paige DG, Lakae BD, Bailey AJ, et al. Restrictive
der-mopathy: a disorder of fibroblasts. Br J Dermatol
14. Happle R, Stekhoven JHS, Hamel BCJ, et al.
Restrictivedermopathy in two brothers. Arch Dermatol
15. Reed MH, Chudley AE, Kroeker M, et al. Restrictive
der-mopathy. Pediatr Radiol 1993;23:617619.
16. Holbrook KA, Dale BA, Witt DR, et al. Arrested
epidermalmorphogenesis in three newborn infants with a fatal
ge-netic disorder (restrictive dermopathy). J Invest
17. Schnur RE, Ashmead J, Kelley RI. A lethal ichthyosisvariant
with arthrogryposis. Am J Hum Genet 1985;37:A76.
18. Hamel BCJ, Happle R, Steylen LAA, et al.
False-negativeprenatal diagnosis of restrictive dermopathy. Am J
19. Dean JCS, Gray ES, Stewart KN, et al. Restrictive
der-mopathy: a disorder of differentiation with abnormal in-tegrin
expression. Clin Genet 1993;44:287291.
CALL FOR PAPERS
The editors of The Syndrome Page welcome submission of your
manuscripts for consideration. Pleasesubmit them in triplicate to
Susan B. Mallory, M.D., Department of Dermatology, St. Louis
ChildrensHospital, 400 S. Kingshighway, St. Louis, MO 63110.
The Syndrome Page 153