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Aplasia cutis congenita(ACC)

MedGen UID:
79390
Concept ID:
C0282160
Congenital Abnormality
Synonyms: ACC; Aplasia cutis congenita (disease); Aplasia cutis congenita nonsyndromic; Congenital defect of skull and scalp; Scalp defect congenital
SNOMED CT: Congenital absence of skin (35484002); ACC - Aplasia cutis congenita (35484002); Aplasia of skin (254237003); Aplasia cutis congenita (35484002); Epitheliogenesis imperfecta (35484002); Cutis aplasia (35484002)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Gene (location): BMS1 (10q11.21)
 
HPO: HP:0001057
Monarch Initiative: MONDO:0007145
OMIM®: 107600
Orphanet: ORPHA1114

Definition

Aplasia cutis congenita (ACC) is defined as congenital localized absence of skin. The skin appears as a thin, transparent membrane through which the underlying structures are visible. The location is usually on the scalp (Evers et al., 1995). Approximately 20 to 30% of cases have underlying osseous involvement (Elliott and Teebi, 1997). Autosomal dominant inheritance is most common, but recessive inheritance has also been reported. Cutaneous aplasia of the scalp vertex also occurs in Johanson-Blizzard syndrome (243800) and Adams-Oliver syndrome (AOS; 100300). A defect in the scalp is sometimes found in cases of trisomy 13 and in about 15% of cases of deletion of the short arm of chromosome 4, the Wolf-Hirschhorn syndrome (WHS; 194190) (Hirschhorn et al., 1965; Fryns et al., 1973). Evers et al. (1995) provided a list of disorders associated with aplasia cutis congenita, classified according to etiology. They also tabulated points of particular significance in history taking and examination of patients with ACC. [from OMIM]

Additional description

From MedlinePlus Genetics
Nonsyndromic aplasia cutis congenita is a condition in which babies are born with localized areas of missing skin (lesions). These areas resemble ulcers or open wounds, although they are sometimes already healed at birth. Lesions most commonly occur on the top of the head (skull vertex), although they can be found on the torso or limbs. In some cases, the bone and other tissues under the skin defect are also underdeveloped.

Most affected babies have a single lesion. The lesions vary in size and can be differently shaped: some are round or oval, others rectangular, and still others star-shaped. They usually leave a scar after they heal. When the scalp is involved, there may be an absence of hair growth (alopecia) in the affected area.

When the underlying bone and other tissues are involved, affected individuals are at higher risk of infections. If these severe defects occur on the head, the membrane that covers the brain (the dura mater) may be exposed, and life-threatening bleeding may occur from nearby vessels.

Skin lesions are typically the only feature of nonsyndromic aplasia cutis congenita, although other skin problems and abnormalities of the bones and other tissues occur rarely. However, the characteristic skin lesions can occur as one of many symptoms in other conditions, including Johanson-Blizzard syndrome and Adams-Oliver syndrome. These instances are described as syndromic aplasia cutis congenita.  https://medlineplus.gov/genetics/condition/nonsyndromic-aplasia-cutis-congenita

Clinical features

From HPO
Aplasia cutis congenita over the scalp vertex
MedGen UID:
370826
Concept ID:
C1970112
Congenital Abnormality
A developmental defect resulting in the congenital absence of skin on the scalp vertex, often just lateral to the midline.

Conditions with this feature

Branchiooculofacial syndrome
MedGen UID:
91261
Concept ID:
C0376524
Disease or Syndrome
The branchiooculofacial syndrome (BOFS) is characterized by: branchial (cervical or infra- or supra-auricular) skin defects that range from barely perceptible thin skin or hair patch to erythematous "hemangiomatous" lesions to large weeping erosions; ocular anomalies that can include microphthalmia, anophthalmia, coloboma, and nasolacrimal duct stenosis/atresia; and facial anomalies that can include ocular hypertelorism or telecanthus, broad nasal tip, upslanted palpebral fissures, cleft lip or prominent philtral pillars that give the appearance of a repaired cleft lip (formerly called "pseudocleft lip") with or without cleft palate, upper lip pits, and lower facial weakness (asymmetric crying face or partial 7th cranial nerve weakness). Malformed and prominent pinnae and hearing loss from inner ear and/or petrous bone anomalies are common. Intellect is usually normal.
Recessive aplasia cutis congenita of limbs
MedGen UID:
324970
Concept ID:
C1838206
Congenital Abnormality
Recessive aplasia cutis congenita of limbs is an extremely rare variant of aplasia cutis congenita (ACC) characterized by the congenital absence of skin on the upper and/or lower limbs, with these lesions usually healing spontaneously resulting in a hypotrichotic scar. Recessive ACC of limbs may be associated with junctional epidermolysis bullosa. The inheritance was hypothesized to be autosomal recessive. There have been no further descriptions in the literature since 1980.
Toriello-Lacassie-Droste syndrome
MedGen UID:
333068
Concept ID:
C1838329
Disease or Syndrome
Oculoectodermal syndrome (OES) is characterized by the association of epibulbar dermoids and aplasia cutis congenita. Affected individuals exhibit congenital scalp lesions which are atrophic, nonscarring, hairless regions that are often multiple and asymmetric in distribution, and may have associated hamartomas. Ectodermal changes include linear hyperpigmentation that may follow the lines of Blaschko and, rarely, epidermal nevus-like lesions. Epibulbar dermoids may be uni- or bilateral. Additional ocular anomalies such as skin tags of the upper eyelid and rarely optic nerve or retinal changes or microphthalmia can be present. Phenotypic expression is highly variable, and various other abnormalities have occasionally been reported, including growth failure, lymphedema, and cardiovascular defects, as well as neurodevelopmental symptoms such as developmental delay, epilepsy, learning difficulties, and behavioral abnormalities. Benign tumor-like lesions such as nonossifying fibromas of the long bones and giant cell granulomas of the jaws have repeatedly been observed and appear to be age-dependent, becoming a common manifestation in individuals aged 5 years or older (summary by Boppudi et al., 2016).
Lethal acantholytic epidermolysis bullosa
MedGen UID:
400622
Concept ID:
C1864826
Disease or Syndrome
Lethal acantholytic epidermolysis bullosa (EBLA) is an autosomal recessive skin disorder characterized by extensive epidermal dislodgment, universal alopecia, and anonychia. Cardiac involvement may be present. Death occurs in the neonatal period (summary by Hobbs et al., 2010).
Scalp-ear-nipple syndrome
MedGen UID:
357183
Concept ID:
C1867020
Disease or Syndrome
Scalp-ear-nipple syndrome is characterized by aplasia cutis congenita of the scalp, breast anomalies that range from hypothelia or athelia to amastia, and minor anomalies of the external ears. Less frequent clinical characteristics include nail dystrophy, dental anomalies, cutaneous syndactyly of the digits, and renal malformations. Penetrance appears to be high, although there is substantial variable expressivity within families (Marneros et al., 2013).
Epidermolysis bullosa simplex 5C, with pyloric atresia
MedGen UID:
436922
Concept ID:
C2677349
Disease or Syndrome
Epidermolysis bullosa simplex 5C with pyloric atresia (EBS5C) is an autosomal recessive genodermatosis characterized by severe skin blistering at birth and congenital pyloric atresia. Death usually occurs in infancy. In reports of 2 consensus meetings for EB, Fine et al. (2000, 2008) considered EBSPA to be a 'basal' form of simplex EB because the electron microscopy shows that skin cleavage occurs in the lower basal level of the keratinocyte, just above the hemidesmosome. There is often decreased integration of keratin filaments with hemidesmosomes. See also forms of junctional EB with pyloric atresia, JEB5B (226730) and JEB6 (619817), caused by mutation in the ITGB4 (147557) and ITGA6 (147556) genes, respectively. For a discussion of genetic heterogeneity of the subtypes of EBS, see EBS1A (131760).
Adams-Oliver syndrome 2
MedGen UID:
481812
Concept ID:
C3280182
Disease or Syndrome
Adams-Oliver syndrome (AOS) is characterized by aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD). ACC lesions usually occur in the midline of the parietal or occipital regions, but can also occur on the abdomen or limbs. At birth, an ACC lesion may already have the appearance of a healed scar. ACC lesions less than 5 cm often involve only the skin and almost always heal over a period of months; larger lesions are more likely to involve the skull and possibly the dura, and are at greater risk for complications, which can include infection, hemorrhage, or thrombosis, and can result in death. The limb defects range from mild (unilateral or bilateral short distal phalanges) to severe (complete absence of all toes or fingers, feet or hands, or more, often resembling an amputation). The lower extremities are almost always more severely affected than the upper extremities. Additional major features frequently include cardiovascular malformations/dysfunction (23%), brain anomalies, and less frequently renal, liver, and eye anomalies.
Linear skin defects with multiple congenital anomalies 2
MedGen UID:
763835
Concept ID:
C3550921
Disease or Syndrome
Microphthalmia with linear skin defects (MLS) syndrome is characterized by unilateral or bilateral microphthalmia and/or anophthalmia and linear skin defects, usually involving the face and neck, which are present at birth and heal with age, leaving minimal residual scarring. Other findings can include a wide variety of other ocular abnormalities (e.g., corneal anomalies, orbital cysts, cataracts), central nervous system involvement (e.g., structural anomalies, developmental delay, infantile seizures), cardiac concerns (e.g., hypertrophic or oncocytic cardiomyopathy, atrial or ventricular septal defects, arrhythmias), short stature, diaphragmatic hernia, nail dystrophy, hearing impairment, and genitourinary malformations. Inter- and intrafamilial variability is described.
Adams-Oliver syndrome 3
MedGen UID:
766662
Concept ID:
C3553748
Disease or Syndrome
Adams-Oliver syndrome (AOS) is characterized by aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD). ACC lesions usually occur in the midline of the parietal or occipital regions, but can also occur on the abdomen or limbs. At birth, an ACC lesion may already have the appearance of a healed scar. ACC lesions less than 5 cm often involve only the skin and almost always heal over a period of months; larger lesions are more likely to involve the skull and possibly the dura, and are at greater risk for complications, which can include infection, hemorrhage, or thrombosis, and can result in death. The limb defects range from mild (unilateral or bilateral short distal phalanges) to severe (complete absence of all toes or fingers, feet or hands, or more, often resembling an amputation). The lower extremities are almost always more severely affected than the upper extremities. Additional major features frequently include cardiovascular malformations/dysfunction (23%), brain anomalies, and less frequently renal, liver, and eye anomalies.
Adams-Oliver syndrome 4
MedGen UID:
815422
Concept ID:
C3809092
Disease or Syndrome
Adams-Oliver syndrome (AOS) is characterized by aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD). ACC lesions usually occur in the midline of the parietal or occipital regions, but can also occur on the abdomen or limbs. At birth, an ACC lesion may already have the appearance of a healed scar. ACC lesions less than 5 cm often involve only the skin and almost always heal over a period of months; larger lesions are more likely to involve the skull and possibly the dura, and are at greater risk for complications, which can include infection, hemorrhage, or thrombosis, and can result in death. The limb defects range from mild (unilateral or bilateral short distal phalanges) to severe (complete absence of all toes or fingers, feet or hands, or more, often resembling an amputation). The lower extremities are almost always more severely affected than the upper extremities. Additional major features frequently include cardiovascular malformations/dysfunction (23%), brain anomalies, and less frequently renal, liver, and eye anomalies.
Adams-Oliver syndrome 5
MedGen UID:
863407
Concept ID:
C4014970
Disease or Syndrome
Adams-Oliver syndrome (AOS) is characterized by aplasia cutis congenita (ACC) of the scalp and terminal transverse limb defects (TTLD). ACC lesions usually occur in the midline of the parietal or occipital regions, but can also occur on the abdomen or limbs. At birth, an ACC lesion may already have the appearance of a healed scar. ACC lesions less than 5 cm often involve only the skin and almost always heal over a period of months; larger lesions are more likely to involve the skull and possibly the dura, and are at greater risk for complications, which can include infection, hemorrhage, or thrombosis, and can result in death. The limb defects range from mild (unilateral or bilateral short distal phalanges) to severe (complete absence of all toes or fingers, feet or hands, or more, often resembling an amputation). The lower extremities are almost always more severely affected than the upper extremities. Additional major features frequently include cardiovascular malformations/dysfunction (23%), brain anomalies, and less frequently renal, liver, and eye anomalies.
Even-plus syndrome
MedGen UID:
904613
Concept ID:
C4225180
Disease or Syndrome
EVEN-plus syndrome (EVPLS) is characterized by prenatal-onset short stature, vertebral and epiphyseal changes, microtia, midface hypoplasia with flat nose and triangular nares, cardiac malformations, and other findings including anal atresia, hypodontia, and aplasia cutis. The features overlap those reported in patients with CODAS syndrome (600373; Royer-Bertrand et al., 2015).
Intellectual disability, X-linked, syndromic 33
MedGen UID:
895979
Concept ID:
C4225418
Disease or Syndrome
X-linked syndromic intellectual developmental disorder-33 (MRXS33) is an X-linked recessive neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, and characteristic facial features (summary by O'Rawe et al., 2015).

Professional guidelines

PubMed

Silberstein E, Pagkalos VA, Landau D, Berezovsky AB, Krieger Y, Shoham Y, Levy A, Rosenberg L, Silberstein T
Plast Reconstr Surg 2014 Nov;134(5):766e-774e. doi: 10.1097/PRS.0000000000000638. PMID: 25347652
Browning JC
Dermatol Ther 2013 Nov-Dec;26(6):439-44. doi: 10.1111/dth.12106. PMID: 24552406
Yilmaz S, Apaydin I, Yenidünya O, Adanali G, Gültan S
Dermatol Surg 1997 May;23(5):402-3. doi: 10.1111/j.1524-4725.1997.tb00074.x. PMID: 9179253

Recent clinical studies

Etiology

Romeo AN, Običan SG
Birth Defects Res 2020 Sep;112(15):1150-1170. Epub 2020 Aug 1 doi: 10.1002/bdr2.1771. PMID: 32738035
Kariminejad A, Vahidnezhad H, Ghaderi-Sohi S, Ghannadan AR, Youssefian L, Parsimehr E, Faraji Zonooz M, Kariminejad MH, Uitto J, Najmabadi H, Hennekam RC
Am J Med Genet A 2019 Aug;179(8):1547-1555. Epub 2019 Jun 11 doi: 10.1002/ajmg.a.61260. PMID: 31184804
Mesrati H, Amouri M, Chaaben H, Masmoudi A, Boudaya S, Turki H
Int J Dermatol 2015 Dec;54(12):1370-5. Epub 2015 May 27 doi: 10.1111/ijd.12707. PMID: 26016611
Mancini AJ
Pediatrics 2004 Apr;113(4 Suppl):1114-9. PMID: 15060207
Whitley CB, Gorlin RJ
Am J Med Genet 1991 Sep 1;40(3):319-26. doi: 10.1002/ajmg.1320400315. PMID: 1951437

Diagnosis

Higgins C, Price A, Craig S
BMJ Case Rep 2022 Sep 13;15(9) doi: 10.1136/bcr-2022-251533. PMID: 36100287Free PMC Article
Kariminejad A, Vahidnezhad H, Ghaderi-Sohi S, Ghannadan AR, Youssefian L, Parsimehr E, Faraji Zonooz M, Kariminejad MH, Uitto J, Najmabadi H, Hennekam RC
Am J Med Genet A 2019 Aug;179(8):1547-1555. Epub 2019 Jun 11 doi: 10.1002/ajmg.a.61260. PMID: 31184804
Manning JR, Lee DH
Pediatr Ann 2019 Jan 1;48(1):e30-e35. doi: 10.3928/19382359-20181212-02. PMID: 30653640
Humphrey SR, Hu X, Adamson K, Schaus A, Jensen JN, Drolet B
J Perinatol 2018 Feb;38(2):110-117. Epub 2017 Oct 19 doi: 10.1038/jp.2017.142. PMID: 29048413
Jones KL, Adam MP
Clin Perinatol 2015 Jun;42(2):243-61, vii-viii. doi: 10.1016/j.clp.2015.02.002. PMID: 26042903Free PMC Article

Therapy

Romeo AN, Običan SG
Birth Defects Res 2020 Sep;112(15):1150-1170. Epub 2020 Aug 1 doi: 10.1002/bdr2.1771. PMID: 32738035
Yang MY, Ha DL, Kim HS, Ko HC, Kim BS, Kim MB
Pediatr Int 2020 Jul;62(7):804-809. Epub 2020 Jul 9 doi: 10.1111/ped.14192. PMID: 32037608
Perry BM, Maughan CB, Crosby MS, Hadenfeld SD
Int J Dermatol 2017 Jun;56(6):e118-e121. Epub 2017 May 8 doi: 10.1111/ijd.13611. PMID: 28480995
Silberstein E, Pagkalos VA, Landau D, Berezovsky AB, Krieger Y, Shoham Y, Levy A, Rosenberg L, Silberstein T
Plast Reconstr Surg 2014 Nov;134(5):766e-774e. doi: 10.1097/PRS.0000000000000638. PMID: 25347652
Mancini AJ
Pediatrics 2004 Apr;113(4 Suppl):1114-9. PMID: 15060207

Prognosis

Schierz IAM, Giuffrè M, Del Vecchio A, Antona V, Corsello G, Piro E
Ital J Pediatr 2020 Feb 18;46(1):25. doi: 10.1186/s13052-020-0789-5. PMID: 32070410Free PMC Article
Perry BM, Maughan CB, Crosby MS, Hadenfeld SD
Int J Dermatol 2017 Jun;56(6):e118-e121. Epub 2017 May 8 doi: 10.1111/ijd.13611. PMID: 28480995
Silberstein E, Pagkalos VA, Landau D, Berezovsky AB, Krieger Y, Shoham Y, Levy A, Rosenberg L, Silberstein T
Plast Reconstr Surg 2014 Nov;134(5):766e-774e. doi: 10.1097/PRS.0000000000000638. PMID: 25347652
Santos de Oliveira R, Barros Jucá CE, Lopes Lins-Neto A, Aparecida do Carmo Rego M, Farina J, Machado HR
Childs Nerv Syst 2006 Sep;22(9):1072-9. Epub 2006 Apr 26 doi: 10.1007/s00381-006-0074-y. PMID: 16639628
Whitley CB, Gorlin RJ
Am J Med Genet 1991 Sep 1;40(3):319-26. doi: 10.1002/ajmg.1320400315. PMID: 1951437

Clinical prediction guides

Raymundo JR, Zhang H, Smaldone G, Zhu W, Daly KE, Glennon BJ, Pecoraro G, Salvatore M, Devine WA, Lo CW, Vitagliano L, Marneros AG
J Clin Invest 2023 Dec 19;134(4) doi: 10.1172/JCI174138. PMID: 38113115Free PMC Article
Coi A, Barisic I, Garne E, Pierini A, Addor MC, Aizpurua Atxega A, Ballardini E, Braz P, Broughan JM, Cavero-Carbonell C, de Walle HEK, Draper ES, Gatt M, Häusler M, Kinsner-Ovaskainen A, Kurinczuk JJ, Lelong N, Luyt K, Mezzasalma L, Mullaney C, Nelen V, Odak L, O'Mahony MT, Perthus I, Randrianaivo H, Rankin J, Rissmann A, Rouget F, Schaub B, Tucker D, Wellesley D, Wiśniewska K, Yevtushok L, Santoro M
J Eur Acad Dermatol Venereol 2023 Mar;37(3):581-589. Epub 2022 Nov 11 doi: 10.1111/jdv.18690. PMID: 36300660
Schnabel F, Kamphausen SB, Funke R, Kaulfuß S, Wollnik B, Zenker M
Am J Med Genet A 2021 Mar;185(3):850-855. Epub 2020 Dec 7 doi: 10.1002/ajmg.a.62009. PMID: 33283961
Schierz IAM, Giuffrè M, Del Vecchio A, Antona V, Corsello G, Piro E
Ital J Pediatr 2020 Feb 18;46(1):25. doi: 10.1186/s13052-020-0789-5. PMID: 32070410Free PMC Article
Irons GB, Olson RM
Plast Reconstr Surg 1980 Aug;66(2):199-203. doi: 10.1097/00006534-198008000-00003. PMID: 6996008

Recent systematic reviews

Hackmon R, Blichowski M, Koren G
J Obstet Gynaecol Can 2012 Nov;34(11):1077-1086. doi: 10.1016/S1701-2163(16)35438-X. PMID: 23231846

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