October 1977 TheJournalofPEDIATRICS
Congenital skin defects and fetus papyraceus Two unrelated infants with congenital skin defects (aplasia cutis congenita) involving the trunk and limbs, each with an associated monozygotie twin fetus papyraceus, are described. Evidence from these two cases and a review of the literature indicate that congenital skin defects of other body areas, as represented by these two children, is a specific pattern of malformation distinct from isolated small congenital skin defects involving the vertex of the scalp. The frequent occurrence of fetus papyraceus in patients with congenital skin defects of other body areas suggests a common etiology for these two phenomena.
Frank L. Mannino, M.D.,* Kenneth Lyons Jones, M.D., and K u r t B e n i r s e h k e , M . D . , L a Jolla, Calif.
CONGENITAL SKIN DEFECTS, also called aplasia cutis congenita, were first reported by Cordon 1 in 1767 in sisters, in whom the skin involvement was limited to the lower extremities. The first cases of CSD affecting the scalp alone were reported in siblings by Campbell. ~ Subsequently, over 475 cases have been reported? Most commonly, affected individuals have an isolated, small, circular midline defect o f the scalp near the vertex, :~'4 though more extensive lesions of the scalp and underlying skull have been reported. Less frequently the defects involve other areas of the body, with or without scalp involvement. These rarer defects often involve extensive areas of the body surface and are frequently symmetrical. Two instances of this rarer type of CSD in unrelated infants, each of w h o m also had an associated fetus papyraceus, are presented. Our purpose is to set foith evidence from these cases and a review of the literature that C S D of other body areas (with or without scalp involvement) is a specific disorder, distinct from CSD of the scalp alone; that the skin defects in this disorder are probably of degenerative rather than aplastic origin; and that the frequent occurrence of fetus papyraceus in patients with CSD of other body areas suggests a c o m m o n etiology for these two phenomena. From the Department of Pediatrics, University of California, San Diego, School of Medicine. *Reprint address: Department of Pediatrics, Mail Code C-019, School of Medicine, University of California, San Diego, La Jolla, CA 92093.
CASE REPORTS Patient 1, a male, was the 2,608 gm product of a term pregnancy, born to a 37-year-old gravida 4, para 3, abortus 1 (6 weeks), VDRL negative, healthy mother, and a 44-year-old healthy father. The other children were normal; no family history of skin defects could be elicited. There was no history of illness or drug ingestion during pregnancy. Labor and delivery were normal except for passage of a fetus papyraceus following artificial rupture of the membranes. A normal amount of amniotic fluid was noted. At birth the infant had absent skin on symmetrical areas of the flanks (Fig. 1). Muscles, blood vessels, fascia, and bone were exposed. The lesions, treated locally with antibiotic ointment, healed with scarring in several weeks. The infant continues to do well at one year of age. Abbreviation used CSD: congenital skin defects Examination of the placenta revealed a monochorionic, diananionic membrane relationship, allowing the diagnosis of monozygosity. The small portion of the placenta which contained the fetus papyraceus was thin, but not completely atrophied (Fig. 2). Microscopic examination revealed no villitis or other abnormality. There were no amnionic bands. The male fetus papyraceus had a 6.5 cm crown-rump length, which indicated a gestational age at death of approximately 11 weeks, and was compressed and distorted. Radiographs revealed a normal skeleton. Numerous irregular brown plaques present on the skin, particularly over the head, right face, and thorax, were shown microscopically to be the result of deposition of amniotic fluid debris, beneath which the epidermis and dermis were thinned. Patient 2, a girl, was born to a 22-year-old mother following a normal 40 weeks' pregnancy and delivery. The infant had skin
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Fig. 1. Skin lesions of Patient 1 at three days of age.
Fig. 2. Placenta and fetus papyraceus of Patient 1.
defects at birth on both flanks just below the ribs, between the anterior and posterior axillary lines, on both knees, and on the left hip and thigh (Fig. 3). No other defects were noted. The lesions healed with scarring and the child is well at three years of age. No family history of skin defects could be elicited. The placenta was monochorionic. A 9 cm long macerated fetus papyraceus was noted in the membranes. Microscopic sections of the placenta revealed no villitis. No amnionic bands were seen. Further description of the fetus papyraceus is not available.
rarely, in large areas on the sides of the head. W h e n scalp lesions occurred with CSD involving other body areas, they were usually o f this u n c o m m o n , more extensive variety. The defects involving-body areas other than the scalp ranged from small lesions on the dorsum of the hand 11 to extensive loss of skin which involved most of the body surface. 12 A high degree of symmetry of lesions on both sides of the body, as noted i n o u r two patients, was characteristic of CSD of other body areas? Histologically, the lesions vary from epidermal defects to full-thickness absence of tissue down to the underlying fascia, with loss of skin organelles such as sweat glands. The usual course is spontaneous healing with scarring. In some cases, partial healing has b e e n noted at birth. Overall mortality from the lesions has been described as 20% but with current therapy the mortality is probably lower. Bleeding and infection are the major causes of death in scalp defects, and infection and skin loss are the major causes of death in CSD of other body areas. The most c o m m o n anomalies associated with CSD of the scalp include defects of the extremities such as terminal transverse defects, polydactyly, and syndactyly. In skin aplasia of other body areas, associated defects of the extremities a n d central nervous system were most common. There were 44 reports of familial CSD of the scalp, representing 110 patients (40% of all CSD of the scalp published). O n e report involved nine cases in three generations of one family. Although the mode of inheritance is usually indeterminate, both autosomal d o m i n a n t and autosomal recessive inheritances have been described. In contrast, there are only rare reports of familial
For this report over 400 cases of CSD were reviewed from the literature. Syndromes in which CSD represent one feature in an overall pattern of malformations such as trisomy 13,5 epidermolysis bullosa,6,, 7 and focal dermal hypoplasia or Goltz syndrome s were excluded, when possible, as were skin defects resulting from intrauterine infections (syphilis, smallpox, varicella, 9 or herpes1~ In this analysis the lesions were Separated into those involving the scalp alone (CSD of the scalp) and those involving other body areas with or without scalp involvement (CSD of other body areas). Features that differentiate these two disorders are set forth in Table I. Although there was documentation that the underlying skull was affected in only 15% of the patients with involvement of the scalp, the true incidence may be much higher because radiographs were not taken in every instance. A remarkable similarity exists in lesions from one patient to another. With respect to CSD of the scalp, the majority of defects were small ( < 3 cm), well-demarcated circular lesions located on the vertex near the midline of the scalp. Less commonly, more extensive lesions occurred in a longitudinal, midline fashion or, even more
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Congenital skin dejects and fetus papyraceus
Table I. Differences between congenital skin defects involving the scalp alone and that involving other body areas
Scalp Number Male/female Scalp Scalp and skull Upper extremity Lower extremity Trunk Face Other anomalies Familial occurrence Twins Fetus papyraceus Monozygotic
Fig. 3. Skin lesions of Patient 2 on the day of birth. occurence of CSD of other body areas; most of these cases represent other syndromes. Only three reports probably represent familial CSD of other body areas?' ,3. 14 One of the most striking features that distinguishes CSD of the scalp from CSD of other body areas is the frequent occurrence of a monozygotic twin fetus papyraceus with the latter disorder. There were 16 reported twin pairs among the patients with CSD of other body areas. One of these cases was dizygotic and only one of the pair was affected? 8 In the other fifteen occurrences each of the associated twins was a fetus papyraceus?' 16-26 Seven of the 15 cases were monozygotic (monochorionic); in eight the zygosity could not be determined from the case reports. These reports are abstracted in Table iI. DISCUSSION Congenital skin defects involving body areas other than the scalp, with or without scalp involvement, comprise a distinct disorder in which the skin lesions are usually
287 0.94 84% 15% 10% 44 8 0 5 (identical lesions in 4)
Other body areas 113 0.94 15% 4% 43% 53% 48% 9% 10% 3 16 (includes one triplet) 15 7 (unknown zygosity in 8)
symmetrical, familial cases are rarely seen, and a markedly increased incidence of monozygotic twinning has been observed. The associated monozygotic twin in all cases has been a fetus papyraceus. A n u m b e r of etiologic possibilities have been proposed for CSD. A m o n g the more frequently mentioned are amniotic adhesions, amniotic bands a n d / o r intrauterine trauma. Abnormal closure of the neural tube 27 or an embryologic arrest of skin development have been suggested as explanations for CSD involving the scalp alone. Most likely, more than one etiology may exist for CSD. The similarity in the clinical phenotype of patients with the disorder herein described suggests a c o m m o n pathogenesis, most likely related in some way to the presence of a fetus papyraceus. A fetus papyraceus is a mummified, dead fetus occurring in association with a viable twin. The death of the fetus usually occurs early in the second trimester. A twin fetus dying very early in gestation may be completely absorbed; later fetal deaths usually result in macerated but not compressed fetuses. 28 Fetus papyraceus occurs rarely, with an estimated incidence of one in 181 twin births. 2~ In a review of 150 cases, Kindred ~~ stated that one-third were monochorionic, a slightly higher incidence of monochorionic m e m b r a n e s than twins in general. All of the documented cases in this series, however, are monochorionic and, therefore, monozygotic. The cause of death leading to fetus papyraceus is usually unknown. Possible etiologies include the twin transfusion syndrome,
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The Journal of Pediatrics October 1977
Table II. Cases of congenital skin defects with a fetus papyraceus
Hochstetter TM Goldberger 17
Diamniotic monochorionic --
von Csatkai 18
1904 1909 1923
Strassman (see LundwalP') Hoeffel2~ BazaF 1
? ? ?
Voron and Bouvier~2
8 cm 3 mo 5 cm
Heijbroek and Carol 23
de Vink~6 Gross 3
Diamniotic monochorionic --
Mannino (Patient l)
Mannino (Patient 2)
6.5 cm 3 mo (abnormal) 9.5 cm
3 mo no examination One FP, one normal infant
Defects Symmetrical flank; thighs Symmetrical flank Thighs; knee Knees; elbows; linear scalp defect Flank Symmetrical flank; back Symmetrical flank Symmetrical flank; thigh; scalp defect Knees
11 cm 4 mo (normal)
Thigh; knees Symmetrical flank; thigh; long midline scalp defect and side of head Knees Symmetrical flank; arms, legs, knees, long midline scalp defect and skull Symmetrical flank Symmetrical flank; thigh, knees
*FP = Fetus papyraceus. cord problems, hemolytic disease, or decidual vascular disease. 28 The most likely possibility to explain the occurrence of twins, one with CSD and the other ~i fetus papyraceus, is that the death of one of monozygotic twins could set off a sequence of events leading to extensive skin defects in the living co-twin. Alternatively, a generalized intrauterine environmental factor might lead to the death of one twin and congenital skin defects in the other. In either case a hemodynamic event related to inter-twin anastomoses of placental blood vessels, a c o m m o n feature in monochorionic twins, 28 m u s t be postulated. Regarding the first possibility, the recently dead twin (i.e., the future fetus papyraceus) may cause vascular thrombosis in utero in the live twin by the passage o f thromboplastic material from the dead twin to the circulation of the live twin (the dead fetus "fouling ''~4 the live twin). We feel that the following evidence gives credence to this hypothesis: In very late gestation t h e death of a monozygotic twin shortly before birth may result in extensive infarcts in m a n y organs of the live-born twin31; this appears to be the result of intrauterine disseminated intravascular coagulation. In
much earlier stages of gestation, the skin may be prone to the effects of such thrombotic phenomena. In the 87% of cases of CSD of other body areas not associated with a fetus papyraceus, a similar vascular etiology may occur, with chorionic thrombosis 2s being the source of thromboplastic material. In addition, a small fetus papyraceus m a y have been overlooked in m a n y o f these cases. If these skin defects are due to thrombotic phenomena, then other organs such as the brain and kidney might be expected to be affected. Pathologic material is scarce but some supporting evidence for involvement of other organs includes three occurrences of C S D of other body areas, without a fetus papyraceus, but with documented structural brain abnormalities? ~-34 Finally, among twin pairs with a fetus papyraceus but without CSD, there are two reports of the associated live twin having intestinal atresia 33 and one of an infant with in utero maceration of the leg 36 all of probable vascular etiology. An episode of hypotension, secondary to variable shunting of fetal blood a n d / o r a generalized decrease in maternal placental blood flow, could lead to demise of one of monozygotic twins and skin defects in the co-twin.
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During a hypotensive episode, areas o f developing skin prone to ischemia (perhaps those areas which are flexed or with poor collateral circulation) may become severely ischemic and skin infarction result. This possibility seems unlikely since we are unaware of any live born monozygotic twins concordant for CSD of other body areas, which may have occurred if an intrauterine environmental factor were operative. Although for purposes of this analysis the u n c o m m o n large scalp defects (both longitudinal and those affecting the sides of the head) were grouped with the more c o m m o n small isolated scalp defect, the etiology of these rarer defects is most likely the same as that of C S D o f other body areas. As noted earlier, 15% of the cases o f CSD of other body areas also had scalp defects and almost all of these were of this large, more rare type. In summary, CSD o f other body areas is most likely a disorder distinct from the more c o m m o n form of CSD involving small, isolated areas on the vertex of the scalp. The placenta of infants with C S D of other areas should be carefully examined for the presence o f a monozygotic fetus papyraceus, since these two disorders are frequently associated. The etiology of these skin lesions is most likely vascular, the insult occurring during the third to fourth month of gestation. Finally, the defects are probably degenerative rather than aplastic and, therefore, the syndrome has been inappropriately named. ADDENDUM Since submission of this manuscript we have learned o f an infant (from Dr. Fife and Dr. Ellwein, Idaho Falls, Idaho) with a large midline CSD of the scalp and skull who was one of triplets; one triplet was normal and the other was an 8 cm fetus papyraceus who shared a diamniotic-monochorionic placenta (monozygotic) with one of the two live infants (unfortunately, we could not document which one). The placental m e m b r a n e s between the live twins were dichorionic. The authors thank Dr. F.J. Fricker, formerly of Nellis Air Force Base, Las Vegas, Nev., for referring us the first patient and Dr. F.G. Moyer of Allentown, Pa., for the referral of the second patient. We also thank Dorothy Miller for her secretarial assistance.
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Congenital skin defects and fetus papyraceus
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Fowler GW, and Dumars KW: Cutis aplasia and cerebral malformation, Pediatrics 52:851, 1973. 34. Ruiz-Maldonado R and Tamayo L: Aplasia cutis congenita, spastic paralysis and mental retardation, Am J Dis Child 128:699, 1974. 35. Saier FS, Burden L, and Cavenagh D: Fetus papyraceus: An unusual case with congenital anomaly of the surviving fetus, Obstet Gynecol 45:217, 1975. 36. Balfour RP: (letter) Fetus papyraceus, Obstet Gynecol 47:507, 1976.