Clinical Observation on Orbital Teratoma of Delleman Syndrome Diagnosed by Fetal MRI Without Cutaneous Manifestations

Introduction Oculocerebrocutaneous syndrome (OCCS), or Delleman-Oorthuys syndrome, is a rare congenital disorder. It is characterized by a range of features, including skin defects, orbital anomalies (such as microphthalmia/anophthalmia and cysts), and malformations of the central nervous system.1 Over the years, additional manifestations such as vertebral abnormalities, hydrocephalus, and facial clefts have been reported.1–4 Since its initial documentation in 1981, approximately 50 cases of OCCS have been reported in the literature. Fetal magnetic resonance imaging (MRI) is an uncommon diagnostic tool for this syndrome.4,6 We observed a unique case of OCCS where fetal MRI findings were obtained, but no cutaneous manifestations were evident at birth. Histopathological examination of the orbital anomaly revealed a teratoma. To our knowledge, orbital teratoma in OCCS without cutaneous manifestations has not been reported, suggesting a need to reconsider diagnostic criteria. Written informed consent was obtained from the pregnant woman for using her medical data in this study, and patient identity has been omitted to protect privacy. Clinical observation This study presents the case of a healthy pregnant woman who was referred to the radiology department for a fetal MRI at 31 weeks gestation due to inconclusive ultrasound findings. During routine antenatal care at 20 weeks gestation, ultrasound (US) revealed a large cystic left orbital mass. Due to the limited field of view on US, further fetal MRI without sedation was performed to delineate the tumor extension. Fetal MRI at 31 weeks’ gestation demonstrated a large cystic mass in the left orbit, lacking a normal ocular bulb, with a solid component at the posterior aspect and no evidence of intracranial extension (Fig. 1A). Additionally, fetal brain MRI revealed colpocephaly, complete agenesis of the corpus callosum (CCA) without a midline cyst, dysplastic left frontal lobe, and a giant tectum (Fig. 1B&C). The posterior fossa showed an absent vermis and a connection between the fourth ventricle and the cistern magna (Fig. 1D). The right orbit was normal, and the head circumference (28 cm) was within normal limits. The gyration of the right cerebral hemisphere corresponded to gestational age, and there were no cleft lip, palate, or skeletal anomalies. Chest and abdominal organs were also within normal limits.Figure 1.: Axial and sagittal T2-weighted fetal MRI of 33 weeks fetus demonstrating crucial observations in brain anatomy and pathology. A A cystic dysplastic left eye with a posterior solid component is discernible, concurrent with the absence of the cerebellar vermis (indicated by the arrow). B The presence of colpocephaly. C A giant tectum in an oval configuration (indicated by the star), in association with a dysplastic left frontal lobe that is of a smaller size compared to the right (arrow). D Complete agenesis of the corpus callosum, accompanied by a giant tectum (indicated by the arrow) and persistent absence of the cerebellar vermis.The female baby was delivered by cesarean section, weighing 3.1 kg, with an APGAR score of 8/10 at one minute and 9/10 at five minutes. The baby appeared healthy overall, except for a large, protruding, soft, red mass in the entire left orbit, not concealed by the eyelid, with no ocular structure present. No cutaneous lesions or seizures were observed. The parents had no significant medical history, no exposure to teratogenic agents during or shortly before pregnancy, no history of miscarriage, and no family history of related malformations. There was no consanguinity and no history of orbital or central nervous system disorders in first-degree relatives. Furthermore, no similar cases have been noted within the families of the parents. Post-natal MRI at three months old was performed for preoperative mapping, showing a dysplastic left eye with cystic and solid components. The intraocular part of the optic nerve blended with the solid orbital mass without intracranial extension and no dilatation of the left optic nerve canal (Fig. 2A). Other findings, such as an enlarged mesencephalic tectum in association with an absent cerebellar vermis and complete agenesis of the corpus callosum, were clearly seen during prenatal MRI examination (Fig. 2B). Cortical dysplasia and heterotopia were more clearly seen on postnatal MRI (Fig. 2C&D).Figure 2.: Postnatal MRI of 3-month-old infant. A Axial T2-weighted image showing a cystic dysplastic left eye with a solid component at the posterior aspect, along with the absence of the cerebellar vermis (indicated by the arrow). B Sagittal T1-weighted image presenting complete agenesis of the corpus callosum, a nodular and enlarged mesencephalic tectum, and the absence of the cerebellar vermis. C Coronal T2-weighted image showing asymmetry of the frontal lobes, with potential focal abnormalities. D Axial T2-weighted image revealing that the left frontal lobe is smaller and exhibits cortical dysplasia and heterotopia, indicating potential neurological abnormalities.The baby underwent surgical resection of the tumor, and histopathology revealed an immature cystic teratoma due to the presence of primitive neuroepithelium. Since immature teratoma has malignant tendencies, the patient underwent further chemotherapy. Discussion Delleman syndrome, first described in 1981,1 is a rare disorder characterized by congenital orbital, cutaneous, and brain malformations. OCCS poses a diagnostic challenge due to its rarity and is often reported postnatally.1,2,5,7,8 While ultrasound technology has advanced, its sensitivity in identifying fetal abnormalities is limited. Fetal MRI, a safe option during pregnancy, can overcome these limitations, especially in cases of high maternal body mass index, oligohydramnios, or atypical fetal position. MRI demonstrates superior sensitivity in identifying central nervous system anomalies compared to 2D and 3D ultrasonography.6 In prenatal ultrasound, the identification of any eye anomalies and brain malformations should raise concerns regarding syndromic disorders like OCCS. It is imperative to conduct a detailed assessment through MRI following any abnormal ultrasound findings with limited field of view to accurately diagnose and evaluate the extent of these conditions, especially when they involve multiple organ systems. Prior to the MRI era, few reports comprehensively emphasized cerebral malformations in OCCS. MRI excels in detecting brain malformations, especially those related to the posterior fossa and cortical development. The brain malformations in this case were similar to previously reported cases, including mid-hindbrain malformation with CCA, colpocephaly, giant tectum, and absent vermis (GTAV), left frontal lobe polymicrogyria, and heterotopia.2,3,5,6 In this case, cortical malformation was ipsilateral to the orbital lesion. The GTAV findings were useful in differentiating OCCS with Dandy-Walker spectrum malformation.3 Integrating ultrasonography and MRI in clinical settings is advisable, as fetal MRI can provide supplementary information (https://links.lww.com/MFM/A61) influencing counseling and management. MRI’s excellent natural contrast determines the nature and extension of orbital lesions. Prenatal MRI in this case showed anophthalmia and a cystic lesion filling the left orbit with a solid component, without intracranial invasion. Orbital teratomas, rare in OCCS, have a propensity for recurrence and malignancy, necessitating revisions to diagnostic criteria, treatment protocols, and prognosis evaluations.8,9 MRI cannot detect skin lesions, but revised diagnostic criteria for OCCS allow for a prenatal diagnosis if two systems are involved with major criteria in both. In this case, congenital orbital cyst fulfilled ocular criteria, and midbrain-hindbrain malformations fulfilled neurological criteria. Fetal MRI plays a crucial role in diagnosing OCCS and determining prognosis by specifying orbital lesion nature and concomitant cerebral malformations.6 The cause of OCCS is unknown, with most cases being sporadic. Some researchers suggest somatic mosaicism in the fifth or sixth week of fetal development. To determine the cause, genome sequencing on tissues from multiple lesions is the primary goal.3,10 Differential diagnoses include Aicardi, Haberland, Goltz, and Goldenhar syndromes. The main differential diagnosis in this case is Aicardi syndrome, which is almost exclusive to females and lacks GTAV, a pathognomonic feature of OCCS.11 Aicardi syndrome is defined by infantile epileptic spasms, chorioretinal lacunae, and corpus callosum agenesis, which were absent in this case.3 Haberland syndrome differs from Delleman syndrome in several aspects, including the absence of orbital cysts and CCA, and frequent intracranial lipomas.3,6 Goltz and Goldenhar syndromes typically present with orbital cysts and skeletal anomalies but lack intracranial anomalies.1 MRI findings enhance the clinical management of syndromes linked to neurological and structural abnormalities, akin to OCCS. MRI aids in diagnosis, monitoring, treatment planning, and disease progression prediction, without using ionizing radiation. This advantage is crucial for regular evaluations, highlighting X-ray limitations. Recognizing brain abnormality patterns helps predict treatment responses, like antiepileptics or physical therapy. Incorporating fetal MRI into the diagnostic pathway for conditions like OCCS in low- and middle-income countries (LMICs) presents a range of challenges and opportunities. While accessibility and cost may pose significant challenges to its widespread use, the application of ultrasound with high resolution as a screening tool offers encouraging prospects. By focusing on collaborative approaches, LMICs can improve the early diagnosis and management of complex syndromes such as OCCS, thereby enhancing patient outcomes in resource-limited settings. Conclusion Fetal MRI plays a pivotal role in the definitive diagnosis of OCCS by identifying orbital lesions and predicting prognosis through the characterization of cerebral malformations. GTAV serves as a diagnostic indicator for OCCS. The absence of cutaneous manifestations does not necessarily exclude OCCS if other major diagnostic criteria are present. This particular case demonstrates that cystic immature teratoma can manifest as an orbital lesion in OCCS. Funding None. Author Contributions Dewi Asih: Radiology workup, manuscript writing, and submission; Utami Purbasari: Coordinator and methodology consultant; Gatot Abdurrazak: Ultrasound workup and prenatal data collection; Audrina Ernes: Radiology data collection. Conflicts of Interest None. Data Availability All data generated or analyzed during this study are included in this published article and its supplementary information files, https://links.lww.com/MFM/A61.