Aplasia cutis congenita (ORPHA:1114)
A rare skin disorder characterized by localized absence of skin that is usually located on the scalp but can occur anywhere on the body including the face, trunk and extremities. Aplasia cutis congenita (ACC) may occasionally be associated with other anomalies.
Epidemiology
Worldwide ACC prevalence is approximately 1/10,000 live births.
Clinical description
ACC is noticed immediately at birth and usually presents as a solitary lesion on or near the vertex. There may also be multiple lesions occurring on the scalp or elsewhere. The individual lesion can vary from a superficial, circular or oval, well-demarcated defect or atrophic scar with alopecia to a weeping or granulating ulcer extending to the bone (non-membranous ACC). The lesions can range from few millimeters to more than 10 cm in diameter. Some defects can have a membranous covering that can be filled with fluid, giving it a bullous appearance (membranous ACC). A tuft of long, dark colored hair (hair collar sign) may be present around the membranous lesion suggesting cranial dysraphism. Membranous ACC is not associated with non-neuroectodermal anomalies. The common Frieden classification subdivides ACC into 9 groups based on cause, localization and associated malformations.
Etiology
Etiology is manifold; genetic factors (including causal mutations in the genes BMS1 (10q11.21) and DLL4 (15q15.1), identified in a few families), teratogens, amniotic adhesion, vascular anomalies, pharmacological agents (e.g. thyreostatics as methimazole, valproic acid, benzodiazepines, heparin) and drugs (cocaine), intrauterine trauma and herpes virus infections have all been implicated. Membranous ACC of the scalp has been proposed to be due to incomplete closure of ectodermal fusion lines whereas non-membranous ACC rather appears to have vascular causes.
Diagnostic methods
Newborns with ACC have to be thoroughly examined for associated anomalies. Extensive cases of ACC necessitate immediate MRI to evaluate any accompanying bone and intracranial malformations. Histologic examination of healed ACC lesions shows scar-like tissue devoid of skin appendages and elastic fibres. Membranous ACC may reveal heterotopic brain tissue.
Differential diagnosis
Differential diagnoses include traumatic lesions, localized scalp infections, dermoid cyst (facial, cervical, nasal or involving the central nervous system), isolated encephalocele, meningocele and nodular neuronal heterotopia. As the child grows and scarring occurs, sebaceous nevus, nevus psiloliparus, localized scleroderma and other types of cicatricial alopecia should be considered. Hypertrophic scars can be mistaken for scalp tumors. ACC can occur in association with inherited epidermolysis bullosa and with epidermal and organoid nevi (didymosis aplasticosebacea). It may also form part of numerous syndromes including: chromosomal abnormalities (mainly trisomy 13), Adams-Oliver syndromes, Johanson-Blizzard, SCALP syndrome, focal facial dermal dysplasia, oculocerebrocutaneous syndrome, scalp-ear-nipple syndrome, Toriello-Lacassie-Droste syndrome, aplasia cutis congenita-intestinal lymphangiectasia syndrome, aplasia cutis-myopia syndrome, cutis verticis gyrata-thyroid aplasia-intellectual disability syndrome, and others.
Antenatal diagnosis
Prenatal diagnosis is limited to ACC types with transmittable genetic origin.
Genetic counseling
Most reported cases of nonsyndromic ACC are sporadic, but autosomal dominant inheritance has been reported in familial cases (including the BSM1 and DLL4 pathogenic variants).
Management and treatment
Biopsy, drainage or excision of lesions should not be undertaken without prior imaging. Treatment of ACC usually involves a conservative approach (gentle cleansing, topical antiseptics, hydrocolloidal dressings) allowing the lesions to heal by secondary intention when possible. Repair using skin flaps and grafts is only recommended for larger defects, such as those extending down to the dura mater, to prevent hemorrhage and infection.
Prognosis
Less severe cases usually resolve within weeks to months, but alopecia persists. Underlying or associated defects may significantly affect mortality and morbidity.

                            Last update: 
                            November 2019


                            - Expert reviewer(s): 
                            Pr Henning HAMM