A Singleton Male Infant With Aplasia Cutis Congenita Type V Associated With Single Umbilical Artery and Atrial Septal Defect: A Case Report

Introduction

Aplasia cutis congenita (ACC) is a rare congenital disorder characterized by localized absence of skin at birth, with an estimated incidence of 1 in 10 000 live births [1–3]. The condition was first systematically classified by Frieden in 1986 into 9 distinct groups based on location, extent, and associated anomalies [4]. Type V ACC is specifically associated with fetus papyraceus or placental infarction and characteristically presents with symmetrical, often stellate or triangular lesions on the trunk and extremities [4,5].

The pathogenesis of Type V ACC is attributed to vascular hypoperfusion during embryonic development, typically resulting from placental insufficiency, twin demise, or umbilical cord anomalies [3,6,7]. Single umbilical artery, occurring in 0.2–1.2% of pregnancies, represents a disruption in normal vascular development and has been associated with increased risk of congenital malformations [3,8,9].

While Type V ACC is typically associated with placental infarcts or a papyraceous fetus, cases linked solely to a single umbilical artery are exceptionally rare. Furthermore, the concomitant finding of a congenital heart defect, such as an atrial septal defect (ASD), has been scarcely reported. Here, we present a case of ACC Type V associated with single umbilical artery and ASD, which, to our knowledge, represents only the second documented case with this specific combination of anomalies, the first being reported by Tekinalp et al in 1997 [10].

Case Report

CLINICAL PRESENTATION:

A male infant was born at 39 weeks’ gestation via cesarean section due to fetal distress and oligohydramnios. Birth weight was 3100 g (25^th percentile), length 49 cm (25^th percentile), and head circumference 34 cm (25^th percentile). Apgar scores were 7 at 1 minute and 8 at 5 minutes. The infant presented with respiratory distress and was immediately admitted to the neonatal intensive care unit (NICU). Supplemental oxygen was administered via nasal cannula at 2 L/min, maintaining oxygen saturation above 92%. Physical examination revealed extensive bilateral skin defects with the following specific anatomical distribution and characteristics:

DIAGNOSTIC STUDIES: HISTOPATHOLOGICAL CONFIRMATION OF SINGLE UMBILICAL ARTERY:

The umbilical cord was submitted for histopathological examination following delivery. Cross-sectional examination of the cord at 3 levels (proximal, mid, and distal) was performed. Microscopic examination using hematoxylin and eosin (H&E) staining revealed a single umbilical artery with a muscular wall thickness of 180–220 μm, a single umbilical vein with a wall thickness of 50–70 μm, normal Wharton’s jelly distribution, no evidence of thrombosis or vessel calcification, and no rudimentary second artery identified on serial sectioning. The single umbilical artery demonstrated the characteristic histological features of compensatory hypertrophy, with increased muscular wall thickness compared with typical umbilical arteries (normal range: 120–180 μm).

PLACENTAL PATHOLOGY:

Complete placental examination was performed according to standard protocols. Gross examination revealed a placental weight of 520 g (appropriate for 39 weeks of gestation; normal range: 400–600 g), no areas of gross infarction were identified, no fetus papyraceus or remnants of twin pregnancy were found, and there was a central umbilical cord insertion measuring 45 cm in length. Microscopic examination of representative sections from the central and peripheral placental zones showed no extensive areas of infarction, mild focal villous ischemic changes (affecting <5% of parenchyma) consistent with decreased perfusion, normal villous maturation for gestational age, no evidence of chorioamnionitis or funisitis, and no vascular malformations were identified.

ECHOCARDIOGRAPHIC DIAGNOSIS OF ATRIAL SEPTAL DEFECT:

Transthoracic echocardiography was performed on day 3 of life using a pediatric phased-array transducer. Two-dimensional imaging revealed a secundum ASD measuring 8 mm in diameter in the region of the fossa ovalis, with left-to-right shunt confirmed on color Doppler imaging. Peak shunt velocity was 0.9 m/s with a Qp: Qs ratio of 1.4: 1 (mild left-to-right shunt). Normal biventricular systolic function was noted with no pulmonary hypertension (estimated right ventricular systolic pressure: 22 mmHg). The ASD was hemodynamically non-significant at the time of diagnosis, requiring only clinical monitoring without immediate intervention.

GENETIC TESTING:

Karyotype analysis revealed 46 chromosomes, XY, with no chromosomal abnormalities.

HISTOPATHOLOGICAL FINDINGS: A skin biopsy was obtained from the edge of the lesion on day 2 of life. Histopathological examination using H&E staining revealed a complete absence of epidermis with necrotic surface debris overlying disorganized dermal tissue. The dermis demonstrated dense collagenous stroma with fibroblast proliferation (spindle-shaped nuclei), scattered inflammatory cell infiltrate (predominantly lymphocytes), and preserved dermal blood vessels. Complete absence of normal epidermal architecture, hair follicles, sebaceous glands, and eccrine sweat glands was confirmed. These findings were consistent with congenital absence of skin structures, confirming the diagnosis of ACC (Figure 2).

CLASSIFICATION AS TYPE V ACC:

According to Frieden’s classification system, Type V ACC is characterized by fetus papyraceus or placental infarction. Our case meets the criteria for Type V classification through the following diagnostic pathway:

Therefore, our case represents Type V ACC with a single umbilical artery as the vascular compromise mechanism, analogous to but distinct from the more commonly reported association with fetus papyraceus or placental infarction.

TREATMENT AND OUTCOME:

Initial management consisted of surgical debridement of necrotic tissue under general anesthesia on day 3 of life. Prophylactic broad-spectrum antibiotics (ampicillin and gentamicin) were administered for 7 days. Treatment of the skin defects involved the application of cultured human epidermal allografts, followed by coverage with hydrocolloid dressings (sodium carboxymethylcellulose, gelatin, pectin, polyisobutylene, and elastomeric polymers), which were changed every 3–4 days (Figure 1D). Progressive re-epithelialization was observed starting from day 14, with complete wound closure achieved by day 50 of life. No infectious complications, wound dehiscence, or hypertrophic scarring occurred. Follow-up echocardiography at 6 months showed a stable ASD without hemodynamic significance.

Discussion

This case presents a singleton male infant with Type V ACC characterized by extensive, symmetrical truncal and lower extremity lesions associated with a single umbilical artery and an ASD. The diagnosis was confirmed by histopathological examination, which demonstrated a complete absence of epidermis and dermal appendages, with disorganized dermal tissue. Notably, examination of the placenta and umbilical cord revealed a single umbilical artery without evidence of fetus papyraceus or gross placental infarction, and genetic testing excluded chromosomal abnormalities.

The pathogenesis of Type V ACC is fundamentally linked to vascular compromise during critical periods of embryonic skin development (weeks 4–8 of gestation) [11,12]. In normal fetal development, paired umbilical arteries ensure adequate perfusion to developing tissues. A single umbilical artery represents a failure of formation or secondary atrophy of 1 of the 2 umbilical arteries, resulting in compensatory hemodynamic changes in the remaining vessel [13,14].

The symmetrical, bilateral distribution of lesions in our case – affecting the lateral trunk and proximal lower extremities in a mirror-image pattern – strongly suggests a vascular watershed phenomenon. During early embryogenesis, these regions represent peripheral perfusion zones supplied by terminal branches of the umbilical circulation [15]. When perfusion pressure is reduced due to the presence of only a single umbilical artery, these watershed areas are most vulnerable to ischemic injury. The triangular morphology of the lesions, with apices pointing toward the midline, further supports this vascular etiology, as it represents zones of maximal hypoperfusion at the periphery of vascular territories [16,17].

The formation of fibrous bands in the umbilical region likely represents healing of more extensive initial defects through fibrosis rather than normal epithelialization, a phenomenon documented in severe ACC cases where wound healing occurs via scarring of subcutaneous tissues [18]. This fibrotic response, rather than normal re-epithelialization, explains the band-like configuration observed, as described by Ahmed et al [19] in their 2024 report of a similar case, in which the 2 triangular lesions were linked by a narrow band passing just below the umbilicus.

A comprehensive literature review identifies only a limited number of cases reporting symmetrical truncal ACC without documented fetus papyraceus or placental infarction. Table 1 compares our case with 3 key published reports: Suliman et al (2004) [20] and Ahmed et al (2024) [19] reported similar bilateral truncal lesions but did not perform umbilical cord examination or document placental pathology, precluding Type V classification according to Frieden’s criteria. Ahmed et al [19] proposed adding a new group to Frieden’s classification to include cases of isolated non-scalp ACC without identifiable etiology, highlighting the diagnostic challenge posed by this presentation. Tekinalp et al (1997) [10] reported bilateral abdominal ACC with ASD but did not document a single umbilical artery or perform placental examination.

Our case provides strong evidence for Type V classification because: (1) histopathological confirmation of a single umbilical artery documents a specific vascular etiology; (2) placental examination explicitly excluded fetus papyraceus and gross infarction; (3) negative genetic testing ruled out syndromic causes with overlapping phenotypes (eg, Adams-Oliver syndrome), and (4) the symmetrical distribution and triangular morphology align precisely with vascular watershed territories.

Importantly, the striking morphological similarity between our case and that reported by Ahmed et al [19] – both presenting with bilateral triangular truncal lesions connected by fibrous bands near the umbilicus – suggests a shared underlying vascular mechanism. The failure to test for the presence of a single umbilical artery in the Ahmed et al 2024 case may explain why the lesions were not classified under Frieden’s Type V, reinforcing the diagnostic importance of comprehensive umbilical cord examination in all non-scalp ACC cases.

The concurrent finding of an ASD in our patient merits specific discussion. While a direct causal link between a single umbilical artery and cardiac defects has not been established, substantial epidemiological evidence demonstrates that single umbilical artery is a significant risk factor for congenital malformations, including cardiac anomalies [8,12]. Meta-analyses indicate a 2- to 3-fold increased risk of major congenital heart defects in infants with isolated single umbilical artery [11].

We propose that the 3 defects seen in our case (single umbilical artery, ACC, and ASD) represent manifestations of a broader embryonic vascular disruption sequence rather than isolated, coincidental findings. During weeks 3–8 of gestation – the critical period for both cardiac septation and cutaneous vascularization – disruption of normal vascular development could simultaneously affect multiple organ systems [5,13]. The single umbilical artery may represent the primary vascular insult, with ACC and ASD as downstream consequences of inadequate perfusion to developing skin and endocardial cushions, respectively.

This interpretation is supported by the absence of other syndromic features and negative genetic testing, which argues against a common genetic mutation causing multiple independent malformations. Instead, the pattern suggests a vascular disruption sequence initiated by abnormal development of the umbilical artery. This underscores the clinical importance of comprehensive cardiac evaluation in all cases of Type V ACC.

The successful conservative management of our case using human epidermal allografts demonstrates the efficacy of this approach for extensive neonatal ACC. Complete re-epithelialization was achieved within 50 days without major surgical intervention, avoiding the risks and morbidity associated with extensive skin grafting in a neonate [2]. Conservative management with silver sulfadiazine, as used by Ahmed et al [19], also achieved complete healing within 2 months, further validating the conservative approach for extensive non-scalp ACC. However, the use of human epidermal allografts in our case provided an additional biological scaffold for re-epithelialization, potentially contributing to the complication-free outcome.

Conclusions

We report a case of Type V ACC associated with a histopathologically confirmed single umbilical artery and ASD in a singleton male infant. This case makes several important contributions to the clinical understanding of Type V ACC: First, it reinforces that a single umbilical artery should be considered a key etiological factor in non-scalp ACC presenting with symmetrical truncal distribution, even in the absence of fetus papyraceus or gross placental infarction. The striking morphological similarity with the case reported by Ahmed et al [19] further supports this hypothesis. The vascular hypoperfusion hypothesis is strongly supported by the watershed pattern of skin involvement.

Second, it underscores the necessity of thorough examination of the placenta and umbilical cord – including histopathological confirmation of vascular anatomy – in all newborns with ACC. This is essential for accurate Frieden classification and prognostic counseling, and may explain why previously reported similar cases [19,20] were not classified under Type V. Third, the association with ASD suggests that echocardiography should be routinely considered in Type V ACC, as the underlying vascular disruption may affect cardiac development. Our findings support the concept of single umbilical artery-associated vascular disruption as a broader embryonic sequence rather than isolated cutaneous pathology.

Finally, the successful conservative management using human epidermal allografts demonstrates the efficacy of this approach for extensive neonatal ACC, achieving complete re-epithelialization without major surgical intervention. This treatment strategy should be considered first-line therapy in metabolically stable neonates with extensive Type V ACC.