70 Aplasia cutis congenita (ACC) is a clinical description of the absence of the skin at birth, first described by Cordon in 1767.
It is a heterogeneous group of disorders characterized by absence of epidermis, dermis, and, sometimes, subcutaneous tissue, muscle, or bone on one or more parts of the body. The incidence is estimated to be 1 in 10,000 births.
GENETICS/BASIC DEFECTS
1. Etiological theories a. Amniogenic theory
i. Adhesion of the amniotic membrane to the fetal skin might tear off, leaving absent areas of skin
ii. Not supported by the study of placentas because most placentas are normal
b. Vascular theory: assumes thromboplastic material from a fetus papyraceus (mummified dead fetus) as the causes of skin damage
c. Placental abnormalities
d. Biomechanical forces on the vertex during the embryogenesis
e. Intrauterine trauma: a history of trauma in only a minority of cases
f. Intrauterine infections i. Varicella
ii. Herpes simplex
g. Intrauterine involution of a hemangioma h. Teratogens
i. Methimazole ii. Misoprostol i. Genetic factors
2. Frieden’s classification of aplasia cutis congenita a. Group I: ACC of the scalp without multiple anom-
alies: sporadic occurrence or autosomal dominant inheritance
b. Group II: ACC of the scalp with associated limb abnormalities: autosomal dominant inheritance c. Group III: ACC of the scalp with associated epider-
mal, organoid nevus, or epidermal nevus syndrome:
sporadic occurrence
d. Group IV: ACC overlying embryologic malforma- tions: inheritance depending on underlying conditions e. Group V: ACC with associated fetus papyraceous or
placental infarcts: sporadic occurrence
f. Group VI: ACC associated with epidermolysis bullosa: autosomal dominant or recessive inheri- tance depending on the type of the epidermolysis bullosa
g. Group VII: ACC localized to extremities without blis- tering: autosomal dominant or recessive inheritance h. Group VIII: ACC caused by specific teratogens: scalp
(methimazole), any area (varicella, H. simplex)
i. Group IX: ACC associated with malformation syn- dromes
i. Trisomy 13 ii. Trisomy 18 iii. Monosomy 4
iv. Ectodermal dysplasias v. Johanson-Blizzard syndrome vi. Focal dermal hypoplasia vii. 46,XY gonadal dysgenesis viii. Amniotic band disruption complex
3. Aplasia cutis congenita associated with epidermolytic bullosa
a. Simplex
i. An autosomal dominant disorder
ii. Lysis of the epidermis occurring within the cyto- plasm of the basal cell layer
b. Junctional
i. An autosomal recessive disorder ii. Damage at the level of the lamina lucida c. Dystrophic (scarring)
i. An autosomal dominant or recessive disorder ii. Defect situated in the anchoring fibrils attaching
the basal lamina to the dermis
CLINICAL FEATURES
1. Aplasia cutis of the scalp (aplasia cutis vertices) a. The most common form
b. Single or multiple noninflammatory ulcers c. Occurrence at or near the scalp vertex d. Variable in shape and size
e. Heals leaving a hairless scar f. Occurrence
i. An isolated condition
ii. Associated with other congenital abnormalities 2. Aplasia cutis with extracranial symmetrical involve-
ment (a distinctive type of “nonscalp” aplasia cutis con- genita)
a. Linear lesions with a symmetrical pattern of distribu- tion on the trunk and limbs
b. Aplasia cutis with fetus papyraceous: usually associ- ated with in utero death of a monozygotic twin dur- ing pregnancy, with or without the presence of a fetus papyraceous (persistence of a mummified dead fetus)
c. Other terms
i. Truncal aplasia cutis
ii. Bilateral abdominal aplasia cutis 3. Associated congenital anomalies
a. Craniofacial anomalies i. Microphthalmia ii. Colobomas iii. Myopia
Aplasia Cutis Congenita
APLASIA CUTIS CONGENITA 71
iv. Epibulbar dermoid v. Cleft lip
vi. Cleft palate vii. Ear malformations b. CNS malformation
i. Hydrocephalus ii. Mental retardation iii. Spastic paralysis c. Ectodermal dysplasia
i. Hypoplasia of the teeth ii. Delayed dentition iii. Nail hypoplasia
iv. Skin blisters
v. Skin hyperpigmentation vi. Cutis marmorata
d. Gastrointestinal abnormalities
i. Tracheoesophageal fistula/esophageal atresia ii. Omphalocele
iii. Gastroschisis
iv. Pyloric atresia: especially in association with junctional (atrophicans) type of epidermolysis bullosa
v. Ileal atresia
vi. Mesenteric herniation vii. Biliary atresia viii. Midgut atresia
ix. Intestinal lymphangiectasia e. Musculoskeletal abnormalities
i. Arthrogryposis ii. Polydactyly iii. Syndactyly 4. Prognosis
a. Scalp lesion (1–3 cm): resolves spontaneously in majority of cases (>85%)
b. Prognosis usually determined by underlying anom- alies and extent of the lesions
DIAGNOSTIC INVESTIGATIONS
1. Imaging
a. Radiography i. Scalp/skull ii. Hands iii. Feet
b. CT scan or MRI of the brain
2. Karyotyping to detect chromosome abnormality 3. Histology: heterogeneous appearance of lesions
a. Ulcerated lesions at birth
i. Complete absence of all layers of skin ii. Occasionally extending to the bone or dura b. In utero healing of some lesions
c. Healed lesions
i. Flattened epidermis
ii. Proliferation of fibroblasts in a loose connective tissue stroma
iii. Newly formed capillaries
iv. Complete absence of adnexal structures 4. Culture/serology
a. Varicella zoster b. H. simplex virus
5. Amniotic fluid findings in some cases a. Elevated amniotic fluid AFP levels b. Positive acetylcholinesterase
GENETIC COUNSELING
1. Recurrence risk a. Patient’s sib
i. Autosomal dominant: not increased unless a par- ent is affected
ii. Autosomal recessive: 25%
b. Patient’s offspring
i. Autosomal dominant: 50%
ii. Autosomal recessive: not increased unless the spouse is a carrier
2. Prenatal diagnosis
a. Ultrasonography for at risk family with aplasia cutis congenita associated with epidermolysis bullosa and pyloric atresia
i. Hydramnios ii. A dilated stomach iii. A deformed external ear
iv. A contracted fisted hand
b. Amniocentesis for associated chromosomal abnor- mality
3. Management
a. Careful and standard wound treatment for small defects involving only epidermis: usually uneventful healing of the lesion
b. Control of infection
c. Control of electrolyte abnormalities, especially with larger wounds
d. Requires a scalp flap for most lesions
e. A split-thickness skin grafting or full-thickness pedi- cle grafts (for defects of the scalp extending to the dura mater)
f. Reconstruction of skull and scalp for a large lesion involving scalp, skull, and dura
g. Emergency intervention to control life-threatening hemorrhage
h. Surgical intervention also useful later in life for revi- sion of scars and correction of alopecia with rotation flaps, simple excision and closure, scalp reduction techniques, or local hair transplantation
i. Management of associated anomalies
REFERENCES
Achiron R, Hamel-Pinchas O, Engelberg S, et al.: Aplasia cutis congenita asso- ciated with Epidermolysis bullosa and pyloric atresia: the diagnostic role of prenatal ultrasonography. Prenat Diagn 12:765–771, 1992.
Al-Sawan RMZ, Soni AL, Al-Kobrosly AM, et al.: Truncal aplasia cutis con- genita associated with ileal atresia and mesenteric defect. Pediatr Dermatol 16:408–409, 1999.
Argenta LC, Dingman RO: Total reconstruction of aplasia cutis congenita involving scalp, skull, and dura. Plast Reconstr Surg 77:650–653, 1986.
Boente MC, Frontini MV, Acosta MI, et al.: Extensive symmetric truncal apla- sia cutis congenita without fetus papyraceous or macroscopic evidence of placental abnormalities. Prenat Diagn 12:228–230, 1995.
Cambiaghi S, Gelmetti C, Nicolini U: Prenatal findings in membranous apla- sia cutis. J Am Acad Dermatol 39:638–640, 1998.
Cambiaghi S, Schiera A, Tasin L, et al.: Aplasia cutis congenita in surviving co- twins: four unrelated cases. Pediatr Dermatol 18:511–515, 2001.
72 APLASIA CUTIS CONGENITA
Carmi R, Sfer S, Karplus M, et al.: Aplasia cutis congenita in two sibs discor- dant for pyloric atresia. Am J Med Genet 11:319–329, 1982.
Chitnis MR, Carachi R, Galea P. Familial aplasia cutis congenita. Eur J Pediatr Surg 35:100–101, 1996.
Classen DA: Aplasia cutis congenita associated with fetus papyraceous. Cutis 64:104–106, 1999.
Cowton JAL, Beattie TJ, Gibson AAM, et al.: Epidermolysis bullosa in associ- ation with aplasia cutis congenita and pyloric atresia. Acta Paediatr Scand 71:155–160, 1982.
Cordon M: Extrait d’une lettre au sujet de trois enfants de la même mère né avec partie des extrémités denuée de peau. J Med Chir Pharm 26:556–557, 1767.
De Groot WG, Postuma R, Hunter AGW: Familial pyloric atresia associated with epidermolysis bullosa. J Pediatr 92:429–431, 1978.
Demmel U: Clinical aspects of congenital skin defects. I. Congenital skin defects on the head of the newborn. II. Congenital skin defects on the trunk and extremities of the newborn. III. Causal and formal genesis of congenital skin defects of the newborn. Eur J Pediatr 121:21–50, 1975.
Dror Y, Gelman-Kohan Z, Hagai Z, et al.: Aplasia cutis congenita, elevated alpha-fetoprotein, and a distinct amniotic fluid acetylcholinesterase elec- trophoretic band. Am J Perinatol 11:149–152, 1994.
Evers MEJW, Steijlen PM, Hamel BCJ: Aplasia cutis congenita and associated disorders: an update. Clin Genet 47:295–301, 1995.
Farine D, Maidman J, Rubin S, et al.: Elevated α-fetoprotein in pregnancy complicated by aplasia cutis after exposure to methimazole. Obstet Gynecol 35:996–997, 1988.
Fisher M, Schneider R: Aplasia cutis congenita in three successive generations.
Arch Dermatol 108:252–253, 1973.
Fonseca W, Alencar Am J Cardiol, Pereira RMM, et al.: Congenital malforma- tion of the scalp and cranium after failed first trimester abortion attempt with Misoprostol. Clin Dysmorphol 2:76–80, 1993.
Frieden U: Aplasia cutis congenita: a clinical review and proposal for classifi- cation. J Am Acad Dermatol 14:646–660, 1986.
Gerber M, de Veciana M, Towers CV, et al.: Aplasia cutis congenita: a rare cause of elevated alpha-fetoprotein levels. Am J Obstet Gynecol 172:1040-1041, 1995.
Irons GB, Olson RM: Aplasia cutis congenita. Plast Reconstr Surg 66:199–203, 1980.
Joshi RK, Majeed-Saidan MA, Abanmi A, et al.: Aplasia cutis congenita with fetus papyraceous. J Am Acad Dermatol 25:1083–1085, 1991.
Kelly BJ, Samolitis NJ, Xie DL, et al.: Aplasia cutis congenita of the trunk with fetus papyraceus. Pediatr Dermatol 19:326–329, 2002.
Kosnik EJ, Sayers MP: Congenital scalp defects: aplasia cutis congenita. J Neurosurg 42:32–36, 1975.
Lane W, Zanol K: Duodenal atresia, biliary atresia, and intestinal infarct in truncal aplasia cutis congenita. Pediatr Dermatol 17:290–292, 2000.
Mannino FL, Lyons Jones K, Benirschke K: Congenital skin defects and fetus papyraceous. J Pediatr 91:559–564, 1977.
McCray MK, Roenigk HH: Scalp reduction for correction of cutis aplasia con- genita. J Dermatol Surg Oncol 7:655–658, 1981.
Sybert VP: Aplasia cutis congenita: a report of 12 new families and review of the literature. Pediatr Dermatol 3:1–4, 1985.
Vogt T, Stolz W, Landthaler M: Aplasia cutis congenita after exposure to methimazole: a causal relationship? Br J Dermatol 133:994–996, 1995.
APLASIA CUTIS CONGENITA 73
Fig. 1. An infant with aplasia cutis congenita with epidermolysis bul- losa showing lesions on the face, trunk, and extremities.
