Aplasia Cutis Congenita and Congenital Heart Disease: A Case Report, Highlighting the Limitation of Antenatal Screening

Abstract

Patient: Female, newborn

Final Diagnosis: Aplasia cutis • tetralogy of fallot (ToF)

Symptoms: Aplasia cutis • tetralogy of fallot

Clinical Procedure: —

Specialty: Genetics • Obstetrics and Gynecology • Pediatrics and Neonatology

Objective: Rare disease

Background

Aplasia cutis congenita (ACC) is a rare congenital defect involving localized absence of skin, occasionally associated with deeper tissue anomalies and congenital malformations.

Case Report

We report the case of a full-term newborn presenting with extensive ACC involving 40% of the scalp, alongside multiple congenital heart defects, ultimately consistent with tetralogy of Fallot (ToF). Initial management included conservative wound care, cardiologic and neurologic evaluations, and genetic testing. Despite clinical stability at discharge, the infant was readmitted 3 weeks later with hemorrhagic shock secondary to sagittal sinus bleeding, requiring surgical intervention and intensive care. Subsequent follow-up revealed tonic seizures and radiological findings suggestive of prior mild hypoxic injury. While the Rapid Aneuploidy Detection test confirmed a normal female karyotype (46,XX), whole-exome sequencing was pending; however, Adams-Oliver syndrome was strongly suspected. This case illustrates the diagnostic and management challenges posed by extensive ACC with syndromic associations. It also highlights the limitations of antenatal screening, as no abnormalities were detected during pregnancy despite fetal growth restriction.

Conclusions

The case underscores the need for a multidisciplinary approach, parental education, and long-term follow-up. Early recognition and coordinated care are essential for managing potential complications and guiding prognosis in complex cases of ACC with associated congenital anomalies.

Introduction

Aplasia cutis congenita (ACC) is an uncommon birth defect characterized by the absence of skin in a localized area, with variable size and location. The most common presentation is a solitary, round, crusted, or ulcerated lesion observed shortly after birth near the neonate’s hair whorl [1–3]. Nevertheless, extensive, multiple or bullous lesions occur in rare cases, causing severe hemorrhage and other life-threatening complications [4–6].

The incidence of ACC is estimated at 1 in 3000 to 1 in 10 000 live births, with a highly variable prevalence globally [2,3,7]. A population-based study in Europe conducted from 1998 to 2017, and involving 28 registries from 16 countries, showed a steady overall prevalence around 5.1 per 100 000 births, with significant variations across countries [7].

Regarding management, the therapeutic approach can involve conservative treatment or reconstructive surgery, the technique and extent of which depends on the size of the lesion and presence or not of bone aplasia [4,5,8]. However, ACC can be associated with cranial dysraphism or other congenital malformations, which can greatly influence both management and outcome. These manifestations are highly polymorphic and can affect multiple systems and organs. Genetic or chromosomal abnormalities are also frequently observed in ACC [4,5,9]. In a multinational European study, an associated congenital anomaly was observed in one-third of the cases, with CHD being found in 15.4% of the cases. Chromosomal anomalies were found in 5.2% of the cases, and familial cases accounted for 2% of cases [7]. Therefore, the presence of ACC should lead to exploring potential underlying syndromes and genetic abnormalities that can affect the management strategy and long-term outcomes [10].

We present the case of a newborn with ACC in whom multiple congenital heart defects were diagnosed, raising suspicion of a genetic abnormality and necessitating a multidisciplinary approach for further evaluation and management. We also discuss the feasibility and potential benefits of antenatal screening and management of these abnormalities.

Case Report

A full-term neonate (40+3 weeks gestational age) weighing 3.640 kg was delivered via emergency cesarean section due to an abnormal non-stress test (NST). The baby was admitted to the neonatal intensive care unit (NICU) for evaluation of cyanosis, low Apgar scores, and respiratory distress, raising suspicion of an underlying genetic syndrome.

Maternal and Birth History

The mother, a Saudi woman, had a booked pregnancy and was gravida 3, para 2+1. Her medical history included gestational diabetes mellitus (GDM) controlled with diet and a previous cesarean section for breech presentation. During the current pregnancy, mixed non-specific bacterial growth was detected in her urine culture and vaginal swab at 28 weeks of gestation. Serological tests, including TORCH (toxoplasmosis, rubella, cytomegalovirus, herpes simplex, and HIV) and hepatitis B screening, were negative. There was no history of consanguinity, and her blood type was B+. The pregnancy was complicated by intrauterine growth restriction, necessitating multiple fetal medicine ultrasounds. A scan at 38 weeks showed fetal growth at the 8.4^th percentile, with normal umbilical artery Doppler imaging. At 40 weeks 6 days, the mother was admitted for induction of labor, which ultimately ended in a cesarean section due to abnormal fetal heart tracing.

At birth, the neonate had Apgar scores of 9 at 1 minute and 10 at 10 minutes. The birthweight was 3.640 kg and head circumference was 32 cm. Cord blood gases showed a pH of 7.21, pCO2 of 49.8 mmHg, HCO3 of 16.7 mmoL/L, lactate of 2.6 mmoL/L, and base excess of −7.5.

Initial Examination and NICU Course

Upon admission to NICU, the baby exhibited features of prematurity and respiratory distress but was otherwise active, moving all limbs, with good tone and reflexes. Examination revealed extensive aplasia cutis involving approximately 40% of the scalp area, with an open anterior fontanelle measuring 4 finger widths, absence of underlying bone, and no active oozing (Figure 1). Head circumference was measured twice at 30 cm (decreased from birth measurement of 32 cm).

Figure 1.

ACC appears as large scalp defect extending over frontal and partial area.

Imaging and multidisciplinary evaluations

The neonate initially exhibited respiratory distress but stabilized on room air, maintaining oxygen saturation >95%. No abnormal breath sounds were noted, and respiratory function remained stable throughout the hospital stay.

The cardiologist’s examination revealed a cardiac murmur on auscultation. Echocardiography on day 3 of life (January 30, 2025), revealed a 3×4 mm perimembranous ventricular septal defect (PM VSD), a patent foramen ovale (PFO) with a small shunt, a tiny closing patent ductus arteriosus (PDA) with left-to-right shunting, mild pulmonary valve stenosis (PSPG 27 mmHg), and normal ventricular function. The baby remained hemodynamically stable and did not require cardiac medication or immediate intervention. A follow-up was scheduled for 3 weeks after discharge.

The abdomen was soft and non-distended. The baby was fed expressed breast milk (EBM) and had adequate urine output (6.3 mL/kg/h), with normal stooling.

The neonate demonstrated weight gain, but at discharge its weight was 2.796 kg, reflecting a slight decrease from birth weight.

Neurosurgery was consulted, but no immediate intervention was deemed necessary. An MRI brain scan performed on day 4 of life (January 31, 2025) revealed foci of diffusion restriction, suggestive of a mild hypoxic insult. The superior sagittal sinus and straight sinus appeared equivocal due to calvarial and skin defects, necessitating further evaluation with a CT venogram (CTV) if clinically indicated to rule out venous occlusion.

Management

The baby remained clinically stable throughout the hospital stay, with no seizures, abnormal movements, or significant feeding difficulties.

Plastic surgery was consulted for the management of the scalp defect. Daily dressing with fusidic acid ointment and Surfatulle was applied to prevent desiccation, and pressure on the affected area was avoided.

The baby received a 6-day ampicillin and gentamicin course for suspected sepsis, with no bacteriological confirmation (negative culture after antibiotic therapy start). Inflammatory markers remained low (CRP <3.31). CBC revealed hemoglobin 20 g/dL, WBC 16.47×10⁹/L, and platelets 319×10⁹/L.

The multidisciplinary assessment identified an association between aplasia cutis and multiple congenital cardiac defects, raising the suspicion of an underlying genetic syndrome. Whole-exome sequencing (WES) was recommended, targeting genes associated with ACC, including ARHGAP31, DLL4, RBPJ, NOTCH1, EOGT, DOCK6, BMS1, and TWIST2. The differential diagnosis included genetic syndromes such as Adams-Oliver syndrome, Bart syndrome, and Setleis syndrome, which are known to be associated with ACC and CHD.

The family received comprehensive counseling from all the multidisciplinary teams involved in their infant’s care. Initially, the parents were concerned about the condition and its potential clinical implications. After a thorough discussion of diagnosis, anticipated progression, and management plan, the parents showed a clear understanding and commitment to the plan. They diligently followed the wound-care instructions and remained actively involved throughout their infant’s hospital stay and subsequent follow-up visits. Overall, the parents adjusted well once they had more precise knowledge and support from the medical team.

First Discharge and Follow-Up

Upon discharge on February 9, 2025 (12 days of life), the baby was thriving on oral feeding and had stable vital signs. Discharge medication included vitamin D3 drops (400 IU PO OD), iron drops (3 mg PO BID), and fucidic acid ointment for local wound care. Follow-up appointments included neonatology after 10 days, plastic surgery after 2 weeks, cardiology after 3 weeks, and genetics after 7 weeks.

Readmission

Three weeks after discharge (March 4, 2025), the infant was urgently readmitted to the PICU in a state of hemorrhagic shock secondary to sagittal sinus bleeding. On examination upon admission, the baby was hypotensive and tachycardic with a blood pressure of 52/40 mmHg and a heart rate of 180 bpm. In the emergency department, the infant received 3 normal saline boluses, each at 20 mL/kg, along with tranexamic acid at a dose of 15 mg/kg. Due to the severity of the condition, the baby was intubated for airway protection and stabilization. On the suspicion of sepsis, antibiotic therapy was initiated with intravenous cefepime 175 mg twice daily.

The scalp lesion was assessed by the neurosurgery team in the operating room, where a dark, thick, yellowish slough was found over the previous dressing site. Surgical debridement was performed, and a hemostatic patch was applied. The wound was re-dressed using a layered technique: Surfatulle, followed by Silvercel, gauze, cotton roll, and a crepe bandage.

A brain MRI conducted at that time showed interval resolution of the previously noted tiny foci of restricted diffusion in the left medial thalamus and right cerebral peduncle, with no new areas of diffusion restriction and no evidence of intra- or extra-axial hemorrhage. MRA and MRV were unremarkable, ruling out any major vascular complications.

A repeat echocardiogram, performed on March 5, 2025, revealed findings consistent with stable tetralogy of Fallot (ToF). The infant remained clinically stable and was not on cardiac medication at the time.

Following stabilization in the PICU, multidisciplinary team decision concluded to transferring the infant to the general ward under the care of the neurosurgery team. A dermatology referral was requested for further evaluation of the scalp defect. As per infectious disease recommendations, intravenous cefepime was to be continued for a total of 2 weeks. The family was updated, and a formal report was given to the parents to support extended care coordination.

On March 21, 2025, at 01: 18 PM, the infant – at 1 month 24 days of life – was clinically stable, with no significant overnight events. The infant was feeding well, and vital signs were within acceptable limits. The dressing over the scalp wound remained clean, dry, and intact. The full 14-day course of cefepime was completed and the wound swab analysis revealed no microbial growth. During admission, the infant developed abnormal tonic movements, clinically suspected to be tonic seizures. The neurology team was consulted promptly. A repeat MRI was unremarkable.

Management included initiating levetiracetam at a dose of 20 mg/kg/day divided into 2 doses. In case of further seizures, the status epilepticus management protocol was to be followed. Events were to be video recorded for diagnostic clarity, and a follow-up with the neurologist was scheduled for the post-discharge period.

At the latest follow-up, the final results of the whole-exome sequencing (WES) remain pending. Genetic counseling showed no structural abnormalities, and the Rapid Aneuploidy Detection test confirmed a normal female karyotype (46,XX). However, given the association of aplasia cutis congenita, congenital heart defects, and recent neurological manifestations, Adams-Oliver syndrome is currently highly suspected as a potential underlying diagnosis. Parental education and further genetic investigations have been prescribed.

Discussion

This case was a rare combination of ACC and CHD – namely, ToF – raising concerns about an underlying genetic syndrome and the feasibility of antenatal screening and diagnosis. Follow-up was marked with hemorrhagic shock secondary to sagittal sinus bleeding and suspected sepsis, with no neurological or further complications. The case underscores the necessity of a multidisciplinary approach in managing congenital anomalies, ensuring optimal long-term outcomes through careful surveillance and coordinated care.

One notable clinical feature in this case was the reported ‘features of prematurity,’ although it was a full-term baby, as reported by the obstetric and pediatric teams and confirmed by the NICU team. While such features have not been reported in the literature, non-isolated ACC is often associated with higher prematurity rates [11].

The first challenge in this case was the initial diagnosis and management, which required coordinated multidisciplinary interventions to evaluate the extent of lesions and associated anomalies, and to determine and implement an appropriate care plan. The early cardiologic investigations showed features consistent with a complex CHD, suggestive of an incomplete or evolving form of ToF due to normal ventricular function and absence of overt cyanosis. Subsequent assessments confirmed ToF diagnosis. ToF is one of the most common CHDs observed in non-isolated ACC, along with atrio-ventricular septal defects and hypoplastic left heart [7]. Exploration of the other systems, notably neurological, gastrointestinal, and ophthalmological, showed no further associated abnormalities in our case.

Actually, ACC is classified into 9 categories, based on lesion localization, associated malformations, and inheritance patterns. The classification was originally proposed by Frieden and revised by Sathishkumar et al [12]. Type 1 represents isolated, non-syndromic scalp ACC, usually sporadic or autosomal dominant. Type 2 is syndromic, associated with limb and cardiovascular anomalies, typical of Adams-Oliver syndrome, with both autosomal dominant and recessive forms. Other types of ACC are linked to other structural malformations, genetic syndromes, teratogenic exposures, or skin fragility disorders, reflecting the broad clinical and etiological heterogeneity of the condition [12].

The present case was classified as type 2, pending the genetic testing results. In a case series by Baroudi et al, 3 female neonates with ACC had suspected Adams-Oliver syndrome, all presenting with large skin lesions and additional congenital anomalies. CHD was confirmed in 1 case and suspected in another. Adams-Oliver syndrome was clinically suspected in the first case due to the combination of a large scalp defect and terminal limb anomalies, although the diagnosis could not be confirmed before the infant’s death. The second case involved an extensive scalp lesion associated with intestinal obstruction; however, no cardiac anomaly or Adams-Oliver syndrome was diagnosed before the patient’s death. The third case, featuring a smaller fibrotic scalp lesion, presented with multiple cardiac abnormalities, including PFO, VSD, tricuspid insufficiency, and severe pulmonary stenosis, suggestive of syndromic association, although Adams-Oliver syndrome was not explicitly diagnosed. The outcomes were poor in the first 2 cases, both resulting in early neonatal death, while the third infant survived with ongoing cardiac evaluation [13].

The second challenge in this case was the readmission for severe bleeding leading to hemorrhagic shock. Given the severity of the presentation and the associated risk of sepsis, the patient was treated with antibiotic therapy along with management for hypovolemic shock. Sagittal sinus bleeding and infection are dreaded complications associated with poor prognosis and high mortality [4,14]. This risk is more pronounced in large defects where major vascular structures such as the sagittal sinus are exposed without protective tissue [15,16]. This was the case for the present patient, who had approximately 40% of the scalp area involved. However, the delayed occurrence of this complication, 3 weeks after discharge, raises concerns about eventual external factors such as trauma or inappropriate handling. Ulterior minor trauma or mishandling of lesions in babies with ACC can precipitate bleeding by disrupting the delicate tissue that covers underlying, often exposed, vascular structures [17]. Thus, recognizing the high sensitivity of ACC lesions to external trauma highlights the need to educate parents and healthcare providers on gentle handling, meticulous dressing, and careful consideration of surgical interventions to prevent hemorrhagic complications. A well-established long-term management plan may be necessary to prevent major events and guide preventive interventions.

Beyond the diagnostic and management challenges, this case raised questions about the relevance and eventual benefits of antenatal diagnosis and management. In our patient, prenatal assessments, including multiple fetal ultrasounds conducted due to intrauterine growth restriction, did not reveal any scalp or cranial abnormalities. Despite careful fetal surveillance, the extensive aplasia cutis involving approximately 40% of the scalp area was only detected postnatally. Furthermore, antenatal ultrasounds failed to detect the CHD. This reflects the inherent limitations of antenatal diagnosis of ACC, especially when the lesion develops later in gestation or when sonographic signs remain subtle. Moreover, although intrauterine growth restriction was noted, which could potentially raise suspicion of underlying syndromic conditions, no specific fetal abnormalities were reported on antenatal imaging.

In practice, antenatal diagnosis of ACC remains challenging due to the subtlety and non-specificity of sonographic signs, particularly in isolated cases without major malformations. Therefore, antenatal diagnosis is more feasible in cases associated with genetic abnormalities [7]. Furthermore, the timing of lesion development (usually in middle to late gestation) can make early detection even more challenging. As such, most cases are identified only postnatally during clinical examination. The reason why antenatal screening for ACC is non-specific is that the condition often does not present with identifiable symptoms or markers during pregnancy. Nonetheless, associations have been noted with multifetal pregnancies, particularly with cases of fetus papyraceus, where 1 twin dies in utero, leading to lesions in the surviving twin due to pressure [18,19].

Prenatal ultrasound plays a crucial role in assessing any associated anatomical anomalies, as certain genetic conditions linked to ACC can be identified through imaging techniques [20,21]. In these instances, detecting abnormal configurations can provide indirect evidence of a potential ACC diagnosis in utero [22]. Other rare instances of extensive ACC may be detected prenatally. Liu et al (2012) reported a twin pregnancy complicated by early intrauterine demise of 1 fetus, with subsequent ultrasound at 32 weeks revealing intrauterine growth restriction and absent abdominal skin in the surviving twin. Ultrasound showed loss of normal echogenicity over the abdominal wall, suggesting exposed liver tissue without intervening skin. No other anomalies were noted, and differential diagnoses such as gastroschisis and omphalocele were excluded. This case demonstrates that, although uncommon, extensive ACC can occasionally be suspected in utero through detailed sonographic assessment [23]. In the present case, prenatal data revealed no findings suggestive of fetal abnormalities that would warrant further investigation. The only noteworthy event was a non-specific bacterial growth detected in a urine culture and vaginal swab at 28 weeks of gestation. All serological test results were negative, and no additional investigations were conducted. It is also worth noting that the mother had a history of GDM and cesarean delivery in previous pregnancies.

Genetic counseling and investigation may be helpful in prompting antenatal diagnosis, particularly in cases with a familial history of ACC or related syndromes, such as Adams-Oliver syndrome, which consists of ACC and limb defects [24]. Awareness of potential teratogenic links to certain medications, such as antithyroid drugs used during pregnancy, may aid in guiding antenatal diagnosis and preventive strategies, underscoring the importance of preconception counseling to mitigate associated risks [20,25]. In the present case, despite a normal female karyotype (46,XX) and no structural anomalies on genetic screening, the combination of ACC, congenital heart defects, and neurological signs raised the suspicion of Adams-Oliver syndrome. WES is pending, and continued genetic follow-up is essential for confirmation and family counseling.

Antenatal diagnosis, when achievable, allows for tailored perinatal management and informed decision-making. Management of ACC typically necessitates a multidisciplinary approach involving pediatric dermatology and plastic surgery. Immediate postnatal care focuses on evaluating the extent of lesions and preventing infection, with more extensive surgical interventions depending on the lesion’s size, location, and associated anomalies. Skin grafts may be considered for larger lesions, while smaller lesions can heal spontaneously with conservative management [26,27]. The prognosis varies significantly based on the characteristics of the lesion and the presence of associated malformations. Comprehensive follow-ups are recommended to monitor for complications such as contractures or developmental delays [28].

Conclusions

This case presents a rare combination of ACC and ToF, suggestive of syndromic ACC under genetic exploration. The skin lesion was treated conservatively and follow-up revealed a hemorrhagic complication and tonic seizures. The case underscores the necessity of a multidisciplinary approach in managing congenital anomalies, ensuring optimal long-term outcomes through careful surveillance and coordinated care. In discussing antenatal diagnosis, the condition remains difficult to diagnose prenatally. Enhancing clinician awareness and integrating fetal imaging with genetic evaluation in selected cases may improve early recognition and inform perinatal planning.