Isolated aplasia cutis congenita: A report of two cases

Abstract

Congenital skin dysplasia, especially isolated scalp defects, is difficult to detect prenatally. The prognosis for isolated congenital scalp defects is good. Treatment options include conservative treatment and surgery. The choice of treatment depends on the patient's individual circumstances.

Congenital skin dysplasia, especially isolated scalp defects, is difficult to detect prenatally. The prognosis for isolated congenital scalp defects is good. Treatment options include conservative treatment and surgery. The choice of treatment depends on the patient's individual circumstances.

1. INTRODUCTION

This study demonstrated two cases of aplasia cutis congenita (ACC) diagnosed after birth. No abnormalities were seen during the antenatal examination of the fetus during pregnancy. The newborn with the larger scalp defect underwent emergency debridement and suturing combine with local flap transfer immediately after birth and recovered well 1 month after surgery. The newborn with a smaller scalp defect was treated conservatively after birth with local disinfection and regular dressing changes, and eventually, a scab was formed, which healed entirely after debridement 1 month after birth. Two children had no hair follicle growth after the healing of the scar. Aplasia cutis congenita may be associated with congenital developmental defects, excessive skin tension, intrauterine infection, or genetics. Early intervention is crucial, and the decision to treat conservatively or surgically should be made concerning the child's general condition, location, and size of the skin lesion.

Aplasia cutis congenital is a rare congenital skin defect with an incidence of approximately 3/10,000, characterized by localized or extensive loss of epidermis, dermis, and occasionally subcutaneous tissue.¹ The exact etiology of ACC is unknown. The disease presents as isolated or multiple lesions that can appear anywhere on the body, but 70%–90% of lesions are localized to the scalp vertex.¹, ², ³ Most ACC tends to heal spontaneously, and its fatal complications include sagittal sinus hemorrhage, meningitis, and brain herniation. The treatment of ACC is controversial. Surgical treatment includes debridement and suturing, local flap transfer, free flap transfer, and skin grafting.² The risks include anesthesia‐related complications, intraoperative bleeding, postoperative infection, and flap necrosis.⁴ Conservative treatment mostly consists of regular dressing changes to promote spontaneous epithelialization, and its risks include bleeding, prolonged healing time, and wound infection.⁵

2. CASE REPORT

2.1. Case 1

The newborn, male, was admitted with “scalp defect found after birth”; mother, 37 years old; father, 40 years old; G3P2, 39 weeks + 1 day of gestation, born by cesarean section due to “scarred uterus,” birthweight 4210 g, Apgar score of 9–9–9, clear amniotic fluid, 600 ml of amniotic fluid, one turn of the umbilical cord around the neck, and no abnormality of the placenta. After birth, a 3 * 2.5 cm scalp skin defect was found on the top of the head, and the skull was visible without bony defects. After being informed of the condition, an emergency debridement and the suture combined with local flap transfer were performed under general anesthesia with tracheal intubation. The operation was successful; postoperative ceftizoxime sodium was used for anti‐infective treatment, and wound dressing was changed. The wound was discharged on the 7th postoperative day, and the stitches were removed 2 weeks after surgery, and the wound healed well on the postoperative review 1 month later. On review 3 months after surgery, the child had no hair follicle growth at the original skin defect on the top of the head and was growing well. (Figure 1) There was no previous history of a similar disease in the child's family, and the child's mother had no history of specific drug exposure during pregnancy. The mother is a gestational diabetic with poor glycemic control and is not using medication to control her blood sugar. Ultrasound in early pregnancy and systemic ultrasound in midpregnancy showed no abnormalities, and Down syndrome screening in early and midpregnancy showed no abnormalities. Because of the advanced maternal age, amniocentesis was performed prenatally for prenatal diagnosis. The karyotype analysis of the fetal exfoliated cells in the amniotic fluid after culture was 46XY for chromosome G dominant band, and chromosome microarray analysis (CMA) showed no increase or deletion in chromosome copy number.

FIGURE 1.

The image of scalp defect

2.2. Case 2

The neonate, male, mother 23 years old, and father 28 years old, was born in our hospital by cesarean section due to “macrodome,” with birthweight 4230 g, Apgar score 9–9–9, clear amniotic fluid, volume 500 ml, and normal umbilical cord placenta. After birth, a skin defect of 1.5 * 1.5 cm was found on the head's top, with a depressed scalp and no local exudation, which was diagnosed as a congenital scalp skin defect. After consultation with dermatology and pediatrics, the child was treated conservatively with topical antibiotic ointment and other medications applied to the skin defect. The scalp defect scars were well healed, and there was no hair follicle growth in the healed area. The child was growing well at 3 months postnatally. (Figure 2) There was no history of similar diseases in the child's family. The child's mother had no abnormal maternal examination during pregnancy with an average Down syndrome screening results. Mother had a history of upper respiratory tract infection in early pregnancy, which improved with traditional Chinese herbs. No record of exposure to other specific drugs and teratogenic substances during pregnancy.

FIGURE 2.

Case 2, the image of scalp

3. LITERATURE REVIEW

3.1. Literature search methods

The literature search was conducted through the China Knowledge Network Data Service and PubMed. The keywords for the Chinese literature search were “先天性皮肤发育不全” and “孤立性头皮缺损,” while the keywords for the English literature search were “aplasia cutis congenita” and “scalp defect.” The exclusion criteria were as follows: (1) patients with congenital dyschondroplasia syndrome; (2) cases with unknown diagnosis and treatment history and incomplete basic information; and (3) repeated cases reported by the same author at the same institution.

3.2. Results

A total of 12 neonates with isolated scalp defects meeting the inclusion criteria were reported nationally and internationally from June 2015 to June 2020 (see Table 1). Among the twelve children, five were males. The largest scalp defect was 9.0 * 10.0 cm, and the smallest was 0.8 * 1.0 cm. Two cases were treated surgically: One case was readmitted for surgery after conservative treatment due to intracranial hemorrhage in the child, and the rest were treated conservatively. All patients survived, and no fatal cases were reported.

TABLE 1.

Clinical profile of children with isolated scalp defects

Data sources	Gender	Scalp defect (cm)	Cranial defects	Treatment
Maeda et al.	Female	8.5 * 8.0	Yes	Conservative
Rocha et al.	Female	9.0 * 10.0	Yes	Conservative
Puvabanditsin et al.	Male	5.0 * 4.0	Yes	Conservative
Lonie et al.	Female	5.5 * 6.0	Yes	Conservative
AlShehri et al.	Female	6.0 * 6.0	No	Conservative
Ghoi et al.	Male	10.0 * 8.0	Yes	Operation after conservative
Orgun et al.	Female	9.0 * 8.0	Yes	Conservative
Xing Li et al.	Male	4.0 * 1.5	Yes	Conservative
	Male	4.0 * 3.0	Yes	Operation
Blionas et al.	Male	10.0 * 5.0	No	Operation
Yuefei He et al.	Female	0.8 * 1.2	Yes	Conservative
Yan Hu et al.	Female	2.0 * 2.0	No	Conservative

4. CONCLUSIONS

4.1. Family history

There was no family history of genetic disorders in both cases, and they choose not to perform whole‐exome sequencing. In the first case, prenatal diagnosis found no karyotype or chromosome microarray abnormalities. In the second case, the mother was screened for Down syndrome, which is normal.

4.2. Maternal conditions

Both mothers had no history of exposure to teratogenic drugs and teratogenic substances during pregnancy. Mothers did not expose to antithyroid drugs, valproic acid, marijuana, heroin, alcohol, and cocaine. The first mother was a patient with gestational diabetes who had poor blood sugar control, and the fetus overgrew during pregnancy. The mother of the second case had a history of upper respiratory tract infection in the first trimester and improved after taking traditional Chinese herbal medicine.

4.3. Defects

The skin defects are only on the top of the head. There is no skin loss in other parts, no malformations of other organs, no heart malformations, and mental retardation.

4.4. Treatment

The first child had surgery to repair the skin defect on the head. The second case was treated conservatively. We use antibiotic ointment to prevent infection, use oil gauze strips and cell growth factors to cover the surface of the skin defect, and change the dressing regularly. The prognosis of the two children was good.

5. DISCUSSION

5.1. Etiology

Aplasia cutis congenita was first reported by Gordon in 1767 and summarized by Campbell in 1826.⁶ It is occurring mainly on the top of the head but can occur anywhere on the body.⁵ Based on the etiology and clinical presentation, Sybert classified ACC into six types. Frieden ranked ACC into nine classes based on the location of the skin defect, clinical symptoms, and genetic factors, as shown in Table 2. The cause of ACC is unknown. Genetics and exogenous factors may play a role in the development of the lesion. Suspected exogenous causes include intrauterine trauma, localized amniotic adhesions, and exposure to teratogenic substances such as antithyroid drugs, valproic acid, marijuana, heroin, alcohol, and cocaine during pregnancy.⁷ The occurrence of ACC has also been associated with skin tears due to excessive tension in the fetal skin and subcutaneous tissues, with the top of the head being the most tensioned area.⁸ The only thing that has been established is that the occurrence of congenital dermal dysplasia is genetically related. Most of these lesions are disseminated, but approximately 25% are autosomal dominant or recessive. Other genetic abnormalities associated with congenital dermal dysplasia include autosomal aberrations, deletions, trisomies, and mutations. No identified genetic target for ACC had been identified, but a recent study suggests a possible role for the BMS1 gene. In a study that examined five generations of autosomal dominant ACC, mutations in the BMS1 gene were found to play an essential role in skin morphogenesis.⁹ ACC can also be associated with various genetic syndromes such as ADAMS‐Oliver syndrome, Bart syndrome, and Setleis syndrome. There was no family history of the genetic predisposition or exposure to drugs and teratogenic substances during pregnancy in both cases. The same point is that both are macrodome, and it is considered that the fetus grew rapidly during pregnancy, causing congenital skin dysplasia due to hypertonicity of the skin tissue on the top of the head.

TABLE 2.

Nine types of ACC (Frieden classification)

Classification	Defect site	Related defects	Genetic factors
Type 1 ACC without multiple malformations	Right at the top of the head	Cleft lip and palate, double uterus, PDA, polycystic kidney	AD/Sporadic
Type 2 ACC with limb abnormalities	Scalp midline	Shortened limbs, deformed feet, missing or malnourished nails, limb redundancy, brain bulge, hemangioma, heart disease	AD
Type 3 ACC with epidermal and organ nevi	Scalp can be asymmetrical	Corneal opacity, scleral sclerosis, eyelid defect, psychomotor retardation, epilepsy	Sporadic
Type 4 ACC with embryonic deformity	Abdomen, waist, any area	Hydrocephalus, spina bifida, cranial stenosis, ectopic ears, leptomeningeal hemangioma disease, umbilical bulge, abdominal fissure	Potential factors
Type 5 ACC with pattern fetus or placental infarction	Multiple, symmetrical, stellate/scalp, chest, lateral abdomen, axillae, ends	Developmental delay, spastic paralysis, nail dystrophy, deformed hands and feet, amniotic girdle syndrome	Sporadic
Type 6 ACC with bullous epidermolysis	End of limb	Skin or mucous membrane blisters, missing or abnormal nails, missing kidneys, clubfoot, herpetic epidermolysis bullosa	AD/AR
Type 7 ACC without bullous epidermolysis	Anterior tibial, dorsal aspect of the hand and foot, extensor aspect of the joint	None	AD
Type 8 ACC due to specific teratogens	Scalp, any area	Anal atresia, a history of herpes and intrauterine infection in the mother of the child during pregnancy	No genetic factors
Type 9 ACC with systemic deformities	Scalp, any area	Trisomy 13, ectodermal dysplasia, amniotic girdle syndrome, XY gonadal dysgenesis syndrome	Individual differences

Abbreviations: ACC, aplasia cutis congenita; AD, autosomal dominant inheritance; AR, autosomal recessive inheritance; PDA, patent ductus arteriosus.

5.2. Pathology

The diagnosis of ACC is usually made only by clinical examination. Because many patients refuse to undergo the local biopsy and cannot be diagnosed pathologically, the diagnosis can only be made based on the patient's age, demographics, and typical scalp involvement. The two children in this article refused the pathological examination. This disease's pathological presentation in the literature is as follows: Histopathological manifestations of nonhealing lesions include epidermal and dermal loss and vascular proliferation. Scar tissue formed at the top of the patient is healed head defect that shows a thin or flattened layer of the epidermis but no attachment structures.

5.3. Treatment

Currently, there are two classification systems commonly used for ACC, namely, the Sybert classification system and the Frieden classification system.¹⁰ The Sybert classification system classifies ACC into six subtypes based on defect location and concomitant symptoms. However, it does not mention the complementary treatment and prognosis. Frieden further analyzes the associated abnormal manifestations of ACC, provides insight into the genetic pattern, and emphasizes the associated pathogenesis. The treatment of patients with ACC depends on the lesion's size and the presence of underlying defects. For small lesions (less than 2 cm) with no additional findings, daily cleaning of the lesion with topical antimicrobial ointment is recommended until healing is complete. Lesions will usually heal within a few weeks to a few months, leaving an atrophic, hairless scar. More extensive lesions (greater than 4 cm) are more commonly combined with underlying defects and have an increased risk of complications, including bleeding, venous thrombosis, and infection.¹¹ Early surgical repair with either a skin graft or a flap repair technique is recommended to avoid these complications.¹¹ For lesions between 2 and 4 cm, conservative treatment or surgical treatment is an option. Conservative treatment includes applying various dressings, continuous rehydration, topical antimicrobial agents, and systemic antibiotics to promote spontaneous epithelialization. Conservative treatment should first be performed in a neonatal intensive care unit with the right monitoring conditions, and then, the child can be cared for at home once the condition is stabilized.¹¹ The advantages of conservative treatment are that it avoids the risks associated with surgery and complications in the donor area. The disadvantages are that it may cause hemorrhage, meningitis, and loss of body fluids from the wound leading to hyponatremia causing brain herniation and seizures. Surgical treatment of congenital scalp defects includes simple debridement and suturing, flap transfer, autologous or allogeneic skin grafting, early or delayed cranioplasty, and tissue expansion. Although the literature reports that cranial defects can be rapidly regenerated, most scholars recommend repairing the skin along with the cranial defect for optimal results.³, ⁴, ⁵, ⁷, ⁸ The surgical treatment complications are mainly due to general anesthesia for tracheal intubation of neonates and the inherent high risk of complex surgical operations.⁹ With medical technology advancements, surgical complications are relatively low, and most of them can be effectively controlled. Compared with conservative treatment, children who underwent surgery had a significantly shorter healing time and fewer postoperative complications. In this report, two children, one treated surgically and one treated conservatively, had good healing of the scalp defect without local or systemic complications.

5.4. Prognosis

Most isolated ACCs without other underlying defects in combination can have a relatively benign outcome.¹ However, when complications occur, the risk of mortality increases dramatically. The most common life‐threatening complication of ACC is sagittal sinus hemorrhage, seen as a lesion near the scalp.³ Another potential complication of ACC includes secondary infection of the lesion. Patients are at increased risk of developing skin infections due to the absence or impairment of the skin's barrier to environmental microorganisms. If not treated properly, severe infections can develop into meningitis. When scalp defects are large, timely surgery can help prevent these complications. ACC patients' skin is replaced by smooth, gray, parchment‐like tissue after healing, with no hair growth. Those with joint deformities are prone to a disability, and those with skin defects that cross the joints may form scar contractures that interfere with function.

CONFLICT OF INTEREST

None declared.

AUTHOR CONTRIBUTIONS

Yan Wu acquired, analyzed, and interpreted data; drafted the initial manuscript; and reviewed and revised it. Jun Liu and Qiong Luo contributed to the analysis and interpretation of the data, contributed to drafting the manuscript, and reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. All authors have read and agreed to the published version of the manuscript.

ETHICAL APPROVAL

The research plan has been approved by the Ethics Committee of Jiaxing University Women's and Children's Hospital. The parents or guardians of the newborn have given written informed consent.

INFORMED CONSENT STATEMENT

Informed consent was obtained from all subjects involved in the study.

Wu Y, Liu J, Luo Q. Isolated aplasia cutis congenita: A report of two cases. Clin Case Rep. 2021;9:e04671. 10.1002/ccr3.4671

DATA AVAILABILITY STATEMENT

Not applicable.