What Syndrome Is This?

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  • THE SYNDROME PAGE

    Editors: Susan B. Mallory, M.D., and Bernice R. Krafchik, M.B., Ch.B., F.R.C.P.C.

    What Syndrome Is This?Jean Graham, M.D.,* and Nancy B. Esterly, M.D.

    *Department of Dermatology, University of New Mexico, Albuquerque, New Mexico, and Medical College ofWisconsin, Milwaukee, Wisconsin

    CASE REPORT

    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 normal lipocytes.

    WHAT IS YOUR DIAGNOSIS?

    Address correspondence to Nancy B. Esterly, M.D., Pediatric Derma-tology, Froedert East, 9200 W. Wisconsin Ave., Milwaukee, WI 53226.

    Figure 1. Characteristic skin changes, contractures, andfacial anomalies.

    Figure 2. Torn skin on the neck and upper chest.

    Pediatric Dermatology Vol. 16 No. 2 151153, 1999

    151

  • RESTRICTIVE DERMOPATHY

    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 abnormalskin.

    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 elasticfibers.

    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, lethal disorder.

    REFERENCES

    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 1980;10:381388.

    7. Carmi R, Sofer S, Karplus M, et al. Aplasia cutis congenitain two sibs discordant for pyloric atresia. Am J Med Genet1982;11:319328.

    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 1988;24:103108.

    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 1983;103:238241.

    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 1992;127:630634.

    14. Happle R, Stekhoven JHS, Hamel BCJ, et al. Restrictivedermopathy in two brothers. Arch Dermatol 1992;128:232235.

    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 Dermatol1987;88:330339.

    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 MedGenet 1992;44:824826.

    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