Aplasia Cutis Congenita

Aplasia Cutis Congenita is a rare disorder with a complicated pattern of inheritance congenital skin defect characterized by a focal or extensive absence of the epidermis, dermis, and occasionally subcutaneous tissue. Babies are born with the absence of certain layer(s) of skin, most often on the scalp, but also the trunk, and/or arms and legs. The affected area is typically covered with a thin, transparent membrane. The skull and/or underlying areas may be visible and be abnormally developed. Aplasia Cutis Congenita may be the primary disorder or it may occur in association with other underlying disorders.

Aplasia cutis congenita (ACC) is a rare congenital skin defect characterized by a focal or extensive absence of the epidermis, dermis, and occasionally subcutaneous tissue. The exact etiology of ACC is not well understood; however, it is likely due to impaired prenatal skin development.

ACC has been classified into six subtypes, some of which are associated with congenital dermatologic syndromes.[rx][rx [rx][rx] Although most lesions are self-healing, certain locations and clinical characteristics should prompt a more thorough workup to screen for underlying soft tissue anomalies that can potentially be life-threatening.[rx]

A classification for ACC was proposed in 1986, which is still accepted today, and presented below.[rx]

Group 1: Scalp ACC without multiple anomalies
Group 2: Scalp ACC with limb abnormalities
Group 3: Scalp ACC with epidermal and organoid nevi
Group 4: ACC overlying congenital malformations
Group 5: ACC with associated fetus papyraceus or placental infarct
Group 6: ACC with epidermolysis bullosa
Group 7: ACC localized to extremities without blistering
Group 8: ACC due to specific teratogens
Group 9: ACC associated with malformation syndromes

Symptoms

Individuals born with Aplasia Cutis Congenital lack skin (and therefore hair), in localized areas of the body, usually, but not always, on the scalp (70 percent of cases). In some cases, the trunk, arms, and/or legs may also be involved. Sometimes, the underlying bone may be missing as well as the skin. The affected area(s) are usually replaced with a thin transparent membrane. In some cases, these affected structures and other organs may be seen through the transparent membrane.

Most individuals with Aplasia Cutis Congenita exhibit no other abnormalities. However, in some rare cases, they may experience other physical characteristics including abnormalities of the ears, a form of paralysis (palsy) affecting one side of the face, an abnormally large head (macrocephaly), and/or congenital heart anomalies.

In 70–80% of cases, aplasia cutis affects the scalp lateral to the midline, but lesions may also occur on the face, trunk, or limbs, sometimes symmetrically.

The areas of skin loss or ulceration vary in size from 0.5 cm to 10 cm.
The defects are non-inflammatory and are well demarcated.
A tuft of hair surrounding aplasia cutis may denote underlying malformation with neural tube defecT.
Superficial aplasia cutis involves only the epidermis (upper layers of skin). Shallow defects usually heal over before the child is born, leaving a scar.
Deeper defects can extend through the dermis, subcutaneous tissue, and rarely periosteum, skull, or dura.
Aplasia cutis may partially heal before delivery and appear as a hairless, atrophic, membranous, parchmentlike or fibrotic scar.
Membranous aplasia cutis is a flat, white membrane overlying a defect in the skull. Distorted hair growth, known as the hair collar sign, is a marker for an underlying cranial defect such as encephalocele, meningocele, and brain tissue outside the skull.
A rare bullous variant of aplasia cutis congenital has been reported.
Some people with aplasia cutis also have congenital malformations of the heart, gastrointestinal, genitourinary (such as gastroschisis or omphalocele), and central nervous systems (such as meningomyelocele or spinal dysraphism).

Aplasia Cutis Congenita may also occur as a physical condition characteristic of several other disorders, including Adams-Oliver Syndrome, Aplasia Cutis Congenita-Gastrointestinal, and Johanson-Blizzard Syndrome.

Causes

Aplasia Cutis Congenita is a rare disorder that may be inherited as an autosomal dominant or autosomal recessive trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.

In dominant disorders, a single copy of the disease gene (received from either the mother or father) will be expressed “dominating” the other normal gene and resulting in the appearance of the disease. The risk of transmitting the disorder from affected parent to offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.

In recessive disorders, the condition does not appear unless a person inherits the same defective gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier of the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers of a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.

Factors contributing to aplasia cutis include:

Genetics: aplasia cutis may be seen in association with other congenital skin defects such as organoid or epidermal naevi. Familial cases are reported with autosomal dominant and autosomal recessive inheritance.
Nonsyndromic aplasia cutis congenital has been associated with a heterozygous mutation in the BMS1 gene (611448) on chromosome 10q11.
Placental infection during pregnancy, such as varicella (chickenpox) or herpes simplex
Teratogens (drugs or chemicals causing birth deformities, such as methimazole, carbimazole, misoprostol, cocaine, marijuana, and valproic acid)
Defects in skin development in the embryo/fetus
Amniotic bands due to early rupture of amniotic membranes
The death of a twin fetus (papyraceous fetus).

Aplasia cutis is rare and no particular race or sex is at greater risk.

Genetics and exogenous factors likely play a role in developing lesions. The suspected exogenous causes include placental infarcts, teratogenic substances like methimazole, intrauterine infections, trauma, and neural tube defects.[rx][rx][rx] Until recently, no specific genetic target had been identified, but a recent study showed the BMS1 gene to play a possible role.[rx] ACC can also be associated with several genetic syndromes, including Adams-Oliver syndrome, Bart syndrome, and Setleis syndrome.[rx][rx][rx][rx]

Related Disorders

Aplasia Cutis Congenita may be one of the symptoms of the following disorders.

Adams-Oliver Syndrome is a rare inherited disorder characterized by the absence of bone in areas of the skull and bald ulcerated areas of the overlying scalp. These skull and scalp abnormalities usually heal spontaneously during the first few months of life, but in a few cases, plastic surgery may be necessary. Limb abnormalities may vary in severity. Fingers and toes may be absent or shorter than normal, and the long bones in the hand may be absent. In some severe cases, the leg below the midcalf may be absent. (For more information on this disorder choose “Adams-Oliver Syndrome” as your search term in the Rare Disease Database.)

Aplasia Cutis Congenita-Gastrointestinal is a rare disorder inherited as an autosomal recessive trait. This disorder is characterized by extensive Aplasia Cutis Congenital and the absence of a normal opening in the canal that goes from below the mouth to the stomach (esophagus), the tube-shaped part of the stomach, and/or the short part of the small intestine that joins the stomach (duodenum). Other symptoms found in some patients with Aplasia Cutis Congenita-Gastrointestinal may be skin separation and/or low-set ears. This disorder is rapidly progressive.

Johanson-Blizzard Syndrome is a form of ectodermal dysplasia that is characterized by nose, scalp, and hair defects, as well as a lack of teeth, deafness, short stature, and a lack of motor development, and malabsorption problems. The most striking feature of this syndrome is the beaklike appearance of the nose. Three-fourths of the patients have a protrusion over the rear fontanelle of the skull at birth which gets thick and hard as the child grows. Their teeth are peg-shaped and they have thin hair that sweeps up from the forehead. Patients with Johanson-Blizzard Syndrome show marked hearing loss from birth as well as motor and mental retardation. Bone growth is delayed and there may be associated intestinal, absorption and genital defects.

Diagnosis

The diagnosis of ACC can typically be made solely from clinical examination. Many providers withhold performing a lesional biopsy given the patient’s age demographics and typical scalp involvement. When a biopsy is necessary to aid in the diagnosis, proper workup, including imaging of the lesion with ultrasound (US) or MRI, is important to ensure there are no underlying malformations that can be damaged during the biopsy procedure.[rx] Histopathologic findings of non-healed lesions include an absent epidermis and/or dermis with a proliferation of blood vessels.[rx] A subtype known as membranous-type ACC will have a thin translucent membrane covering.[rx] Lesions that have already healed with a scar will have a thin or flattened epidermis, absent adnexal structures, and dense, dermal fibrosis noted on pathology.[rx]

History and Physical

ACC can have a variable presentation at birth including an erosion, ulceration, membrane-covered defect, or scar, indicating intrauterine healing. Solitary scalp lesions make up approximately 70% of all ACC cases, although multiple lesions affecting the face, trunk, and extremities can also be seen.[rx][rx] Lesions vary in size from a few millimeters up to several centimeters.[rx] For cases with no underlying defects, ACC will gradually become smaller and ultimately form a scarred defect.[rx]

ACC can be associated with underlying morphologic abnormalities in approximately 37% of cases, according to Maserati et al.[rx] including underlying bony defects, vascular anomalies, or neurologic malformations, so it is prudent for clinicians to evaluate the disease involvement with imaging. A midline vertex scalp lesion, hair collar sign, and vascular stains have all been shown to be strong indicators of cranial or central nervous system (CNS) involvement.[rx][rx] Small, scalp lesions are less likely associated with underlying defects and typically heal on their own within a couple of months; therefore, monitoring these lesions without further imaging is acceptable.[rx] For larger, ulcerative lesions, ultrasound provides a relatively inexpensive evaluation while not putting the child through a great deal of discomfort. If there is any concern for underlying defects on ultrasound, further workup with MRI is warranted. MRI is more sensitive and specific for identifying underlying lesions according to a 2017 retrospective multicenter study[rx]; however, it is more costly than ultrasound and typically requires the child to be sedated for the duration of the procedure, making this a poor choice for initial screening. If the lesion is purulent or surrounded by erythema, a lab workup including complete blood count, blood cultures, and wound cultures would be advised.[rx][rx]

Treatment

Diagnosis of Aplasia Cutis Congenita is generally obvious at birth through the characteristic absence of skin affecting the scalp, trunk, arms, and/or legs.

Children diagnosed with Aplasia Cutis Congenita should receive a complete medical evaluation to determine whether this disorder is occurring on its own or as a secondary characteristic of another disorder. If Aplasia Cutis Congenital is occurring on its own, affected children should be monitored for symptoms and physical characteristics associated with this disorder.

Medical treatments for Aplasia Cutis Congenita include measures to prevent the drying out of the membrane by soothing, bland ointments. Antibiotics should be used only if signs of bacterial infection are present. The damaged area usually heals spontaneously.

Surgical care may include the repair of multiple scalp defects that usually, but not always, respond to procedures less traumatic than skin grafts. These may include such techniques as tissue expanders to fill in large areas or flap rotation to ease a piece of skin over an affected area.

Early surgical repair is recommended to avoid these complications. Skin grafting or flap techniques are commonly utilized as some lesions can be several centimeters in size.[rx]

Genetic counseling may be of benefit for affected individuals and their families.

Aplasia Cutis Congenita

Symptoms

Causes

Treatment

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