Table 1 Classification for Aplasia cutis congenita (ACC), modified [2,3,4]

1-nonsyndromicACC

Scalp, usually paramedian vertex

Occasionally other ectodermal anomalies inclusive supernumerary nipples

AD (BMS1)/sporadic

2-ACC with limb abnormalities

Midline scalp

• Transverse limb defects (Adams-Oliver syndrome)

• Cardiovascular anomalies: congenital heart defects (e.g. Fallot), Cutis marmorata teleangectasica congenita (19%), incomplete retinal vascularization, hemangioma, hepatoportal sclerosis, stenoses of pulmonary and intestinal veins, placental vascular abnormalities, woolly hair

• ocular and CNS malformations

AD (gens ARHGAP31, DLL4, NOTCH1, RBPJ)/AR (gens DOCK6, EOGT)

3-ACC with epidermal nevi

Scalp, symmetrical distribution

• conjuntival and corneal limbal dermoids (oculo-ectodermal syndrome of Toriello-Lacassie-Droste)

• sebaceous nevus, CNS malformations, limbal dermoids, pigmented nevus (SCALP syndrome)

• didymosis aplasticosebacea

sporadic

4-ACC overlying embryologic malformation

Scalp, trunk

meningomyelocele, porencephaly, leptomeningeal angiomatosis, cranial stenosis, spinal dysraphism, gastroschisis, omphalocele, bladder exstrophy

Depending on underlying causes

5-ACC with fetus papyraceus or placental infarcts

Scalp, trunk, extremities (multiple, symmetric areas, often stellate)

Single umbilical artery, fetal growth restriction, limb anomalies, amniotic bands

Sporadic

6-ACC of extremities associated to epidermolysis bullosa

Predominantly extremities

Blistering of skin, gastrointestinal atresies, anomalies of ears, kidneys and skeleton, artrogryposis, nail deformities (Bart syndrome and other dystrophic forms of epidermolysis bullosa)

AD/AR/sporadic

7- ACC of extremities not associated to epidermolysis bullosa

Extremities (extensor areas)

–

AD/AR

8-ACC caused by teratogens

Scalp (methimazole), diffuse (varicella, herpes simplex)

Anorectal malformation (methimazole), hepatosplenomegaly and other signs of intrauterine infections (varicella, herpes simplex), hypertrophic cardiomyopathy in children of diabetic mother

–

9-ACC associated with malformation syndromes

Craniofacial, trunk

• trisomy 13

• 4p deletion syndrome

• Xp22.2 deletion syndrome

• Xp22.31 ectodermal dysplasia

• TP63 associated syndromes (Ectrodactyly, ectodermal dysplasia, and cleft lip/palate syndrome 3; Hay-Wells syndrome; Acro-dermato-ungual-lacrimal-tooth syndrome)

• bitemporal ACC (Brauer, Brauer-Setleis and Setleis syndromes)

• Kabuki syndrome

• intestinal malabsorption (Johanson-Blizzard syndrome)

• intestinal lymphangiectasia (Bronspiegel-Zelnick syndrome)

• oculocerebrocutaneous syndrome with cerebellar anomalies (Delleman syndrome)

• scalp-ear-nipple syndrome (Finlay-Marks syndrome)

• Knobloch syndrome (retinal detachement, occipital primary encephalocele)

• amniotic band disruption complex

Depending on specific syndrome: AD/AR/X-linked/sporadic