Clinical observation of complete oculocerebrocutaneous syndrome in newborn boy is presented. Clinical symptoms of the disease were characterized by right-sided ophthalmological (lipodermoid of conjunctive and upper eyelid, congenital coloboma of iris and optic nerve head, cataract), cerebral (schizencephaly, lissencephaly, pachygyria, arachnoid cyst of posterior cranial fossa, seizures) and cutaneous (congenital alopecia areata, aplasia cutis, atrophic scars, skin atrophy foci) manifestations. Oculocerebrocutaneous syndrome (Delleman syndrome) is a rare genetic pathology, sporadically occurring at 1 case per 500 000 newborn boys. Diagnostic criteria for Delleman syndrome include triad of ophthalmological, cerebral and cutaneous manifestations: congenital abnormalities and malformation of the eyes and brain, tumors and hamartomas of the skin, localized predominantly on the left side of the head. Dysplasia of cerebral cortex, agenesis of the corpus callosum, cerebellar hypoplasia, intracranial cysts, porencephaly, lissencephaly, seizure syndrome manifestations, signs of the delayed psychomotor development are revealed in congenital brain pathology. The ophthalmological symptoms of Delleman syndrome include orbital cysts, anophthalmia or microphthalmia, epibulbar neoplasms and dermoids, cataract, eyelids ectropion, coloboma, glaucoma. Skin manifestations include hypoplasia and aplasia of the skin, periorbital soft fibromas, alopecia areata and totalis, hamartomas and neoplasms of the skin and its appendages, dermoid cysts, lipomatosis of the face and periorbital area, foci of skin hyperpigmentation and hypopigmentation. The peculiarity of the presented clinical case is the rare occurrence of oculocerebrocutaneous syndrome in practice of dermatovenerologists and doctors of other specialties.

Delleman-Oorthuys syndrome is a rare congenital anomaly of unknown aetiology. It is also called Oculocerebrocutaneous syndrome that characteristically involves ectomesodermal tissues such as the eyes, central nervous system, and the integument. We report a 2-year-old boy with an orbital cyst in the left eye along with other manifestations of this disorder since birth. Physical examination revealed a huge left eye cyst. An ultrasound scan of the left orbit showed a huge thick-walled cystic lesion involving the left globe with multiple internal strands and echoes. Computed tomography of the brain revealed severe atrophy of the left cerebral hemisphere in addition to characteristic cerebral malformations of Delleman-Oorthuys syndrome. This report highlights the need for extensive neuroimaging in searching for life-threatening cerebral atrophy; unfortunately, genetic studies that could shed light on this syndrome are not available in our resource-constrained settings.

No abstract availableSri Lanka Journal of Child Health, 2022; 51(3): 484-487

The presence of skin and ocular findings includes syndromes with X linked transmission, such as microphthalmia with linear skin defects (MLS) syndrome, focal dermal hypoplasia (Goltz syndrome), oculocerebrocutaneous syndrome, incontinentia pigmenti and Aicardi syndrome. We report the case of a term neonate with corneal opacities and unusual skin findings along with an encephalocele consistent with MLS syndrome.

Abstract Oculocerebrocutaneous syndrome (OCCS) is a rare disorder with specific clinical presentation. It can be diagnosed clinically upon specific dermatological, neurological, and ophthalmological criterion. We present the case of a 5-week-old baby boy with OCCS syndrome, highlighting its dermatological manifestations and a review of skin features as well. The patient presented with a unilateral microphthalmia with orbital cysts, postauricular crescent-shaped skin defect, and pedunculated skin appendages with multiple focal hypoplastic skin lesions. Early diagnoses and long-term follow-up may improve the prognosis of such a rare disease.

A 4-year-old male child, born to nonconsanguineous parents, was brought with a history of a fleshy red mass in both eyes and abnormally shaped eyelids since birth. Evaluation revealed delayed developmental milestones and temporoparietal alopecia over the right side along with focal areas of hyperpigmented skin over the face, chest, back, and both upper limbs. Ocular evaluation revealed skin tags over the upper eyelids, epibulbar dermoid along with upper lid coloboma, and microcornea in both eyes. He had deformed temporoparietal bones on both sides. Magnetic resonance imaging brain revealed generalized cerebral atrophy with prominent Virchow–Robin spaces and enlarged ventricular system but atypically normal corpus callosum. He was diagnosed as an atypical variant of Delleman syndrome (a rare congenital disorder involving eyes, skin, and brain and comprising orbital cyst, eyelid colobomas, skin appendages, polymicrogyria as well as characteristic mid-hindbrain abnormalities). Multidisciplinary treatment approach and long-term neurological follow-up are recommended in these patients.

Oculocerebrocutaneous syndrome (OCCS) is a rare disorder characterized primarily by congenital skin, eye, and brain anomalies. The most distinctive findings are hypoplastic or aplastic skin defects; pedunculated, typically hamartomatous, or nodular skin appendages; cystic microphthalmia; and a combination of forebrain anomalies and a specific mid-hindbrain malformation. Based on a review of 40 patients with OCCS, existing clinical criteria have been revised. Because of the asymmetric and patchy distribution of features, lack of recurrence in families, male preponderance and completely skewed X-inactivation in one female, OCCS is hypothesized to result from postzygotic mosaic variants in an X-linked gene. Whole exome and genome sequencing on blood DNA in two patients failed to identify pathogenic variants so far. In view of the overlapping features, in particular of the brain, of OCCS and Aicardi syndrome, both may be pathogenetically related or even result from different variants in the same gene. For the elucidation of the cause of OCCS, exome or genome sequencing on multiple lesional tissues is the primary goal.

Due to the efforts of the clinical and scientific communities and boosted by recent advances in genetic technologies, we now understand the molecular mechanisms underlying most of the frequent and recognizable human malformation syndromes. However, some well-established human malformation syndromes remain without a molecular diagnosis despite intensive investigation. This issue of Seminars mines the phenotypic entries in OMIM and estimates that of the documented 2,034 unsolved entries likely to represent a rare genetic disease, only 160 are well-established and possibly amenable to investigation. This issue also reviews well-characterized and extensively investigated human malformation syndromes and associations that remain unsolved, including the following: Dubowitz syndrome (MIM 223370%), Hallermann-Streiff syndrome (MIM 234100%), PHACE syndrome (MIM 606519), Oculocerebrocutaneous syndrome (MIM 164180), Aicardi syndrome (MIM 304050%), Gomez-Lopez-Hernandez syndrome and Rhombencephalosynapsis (MIM 601853%), VACTERL (MIM 192350%), and Nablus syndrome (MIM #608156). Possible explanations for their intractability to molecular diagnosis are explored, including genetic and phenotypic heterogeneity, mosaicism, epigenetics, gene-environment interactions, and other non-Mendelian contributions. Finally, this issue of Seminars presents a path forward for these unsolved rare conditions and suggests a renewed focus on solving amendable OMIM disorders. It is clear that the way forward will require new technologies, global cooperation, and data sharing; these will also be necessary to help reach the vision of the International Rare Diseases Research Consortium (IRDiRC), that is to enable all people living with a rare disease to receive an accurate diagnosis, care and available therapy within 1 year of coming to medical attention.

The occurrence of an accessory palpebral fissure and eyelid is an extremely rare phenomenon. An isolated accessory palpebral fissure and eyelid have been reported only twice in the literature, and in one case as an extension of Delleman syndrome, or oculocerebrocutaneous syndrome. The authors report a case of a full-term newborn who presented with an accessory palpebral fissure and eyelid associated with microcornea, skin polyps and tags, cutis dysplasia, and hypoplasia of the corpus callosum with an otherwise normal systemic workup and negative genetic screening. Detailed surgical management and histopathological analysis of the accessory findings are also described.

Introduction: Oculocerebrocutaneous syndrome (OCCS) is a rare neurocutaneous disorder of unknown etiology. We describe the first case in which cerebrospinal fluid (CSF) was identified within the associated orbital cyst. The CSF fistula was ultimately treated via endoscope-assisted eyebrow craniotomy.

Delleman–Oorthuys syndrome or oculocerebrocutaneous syndrome (OCCS) is a rare genetic disorder characterized by eye abnormalities, skin abnormalities, areas of alopecia in combination with hydrocephalus. Until date, only 28 patients with equivocal diagnosis of OCCS have been reported. All of which are sporadic, with no risk of recurrence in the siblings. No etiological cause has been found as yet. It may also show overlapping clinical features with other syndromes like Goldenhar syndrome, encephalo-cranio-cutaneous lipomatosis and Goltz syndrome. We present a case of a 9-month-old male child who presented with unilateral temporo parietal aloepecia, multiple cystic lesions on the upper eyelid and adjacent periorbital areas, as well as an upper eyelid coloboma and epibulbar dermoid, all of which were present since birth.

Case Report: Two Patients With Oculocerebrocutaneous Syndrome and Terminal Digital Amputations

The authors describe a patient with oculocerebrocutaneous syndrome, also called Delleman-Oorthuys syndrome. This patient is the first reported case in Turkey. The 19-month-old boy had characteristic features of oculocerebrocutaneous syndrome, such as unilateral orbital cyst, skin tags and skin hypoplasia, hypoplastic left cerebellar hemisphere, Dandy-Walker variant anomaly, corpus callosum agenesis, and left cerebral hemispheric diffuse migration anomaly.

There are many congenital ocular malformations associated with systemic findings. In cases such as oculocerebrocutaneous syndrome, the severity of systemic findings makes diagnosis particularly important. This case report presents a case of this uncommon syndrome and demonstrates the common findings.

A case is reported with right-sided abnormalities involving the brain, eyelid, eye, face and chest. The features described are similar to those found in conditions including focal dermal hypoplasia, microphthalmia with linear skin defects, oculocerebrocutaneous syndrome and terminal osseous dysplasia and pigmentary defects. However, none of these conditions, fully explains the collection of abnormalities found in this patient.

The discovery of relevant causative genes has subdued the lumping versus splitting debate with respect to a growing number of syndromes. However, it remains paramount to define unknown genesis syndromes as precisely and appropriately as possible in order to provide accurate prognosis and to facilitate future research. The presentation of a 14-month-old girl, of normal intelligence, who had a colobomatous right eye with cyst, minor intracranial MRI variants, and an area of sparse scalp hair containing a 1 by 1.5 cm, soft, domed, and indented skin lesion suggested a diagnosis of mild oculocerebrocutaneous syndrome (OCCS). An initial exploration of the literature exposed the extreme variability in cases that have been reported as OCCS, and emphasized its possible relationship to encephalocraniocutaneous lipomatosis (ECCL), thus challenging the initial diagnosis. Cases reported, or discussed by others, as possible OCCS (40) and ECCL (44) were reviewed as completely as possible in an effort to determine whether diagnostic criteria could be developed for these syndromes, and to see whether or not evidence favored their continued separation as two syndromes. The approach used was to summarize the data for all cases, to select major and minor diagnostic criteria on the basis of the relative specificity and/or frequency of a sign, to then apply the criteria in a standard fashion and to review the outcome to see if the classification of cases made clinical sense, and to make appropriate adjustments. The criteria were not chosen so as to separate the syndromes and in some instances the same criteria could apply to either syndrome. An approach is outlined for handling reports of patients that purport to be variants or to expand the spectrum of a syndrome, and in the case of OCCS and ECCL this resulted in most such examples being excluded. Application of diagnostic criteria suggests that OCCS and ECCL are distinct, and that some case reports, including some purporting to expand the spectrum of OCCS, should be excluded, at least until such time as the etiology of these conditions is known and those cases can be tested. These diagnostic criteria were developed on the basis of literature reports that varied in their quantity and quality of detail. Furthermore, in many cases reliance had to be placed on copies of original studies with resultant degradation of photographic information. Modern ocular imaging, and histopathology of eye and skin malformations, will often clarify the specific nature of a malformation and, therefore, define exact diagnostic criteria and leave fewer uncertain cases. In the absence of anomalies in those systems, or if histopathology or appropriate imaging is unavailable, the diagnosis in some cases will continue to remain uncertain; this is not an argument for lumping the syndromes.

Background: Oculocerebrocutaneous syndrome (OCCS) is characterised by orbital cysts and anophthalmia or microphthalmia, focal aplastic or hypoplastic skin defects, skin appendages, and brain malformations. The eye and skin abnormalities are...

We describe two cases of oculocerebrocutaneous syndrome (OCCS) or Delleman syndrome, characterized by congenital anomalies that involve the skin, orbit, and central nervous system (CNS). Complete MRI studies of the orbit, CNS and the entire spinal region must be performed in these cases. New MRI techniques can show cortical malformations, such as polymicrogyria, lissencephaly, or abnormal disposition of cortical sulci and gyri. Lesions can be bilateral or unilateral, as occurred in our patients. In one case, the ocular, skin, cerebral, and cerebellar lesions involved mainly the same side, whereas in the second case, all anomalies were generalized and the patient also showed skin hypopigmented lesions distributed bilaterally. Both patients show severe encephalopathy and Dandy-Walker malformation. One case is blind and shows generalized hydrocephalus, and the other one has vision through an eye, and has complete agenesis of the corpus callosum and severe disorder of neuronal migration and cortical organization with polymicrogyria and abnormal cortical sulci and gyri in a cerebral hemisphere. Our second case shows arachnoid cysts in both temporal, retrocerebellar, and spinal (D(8)-D(11)) regions, and lipoma in the pontomedullary and spinal (D(4)-D(7)) regions. The latter features correspond more to ECCL than to OCCS. The overlap between the two syndromes is unquestionable and it is possible that they constitute different manifestations of the same disorder.

Regional skin hypoplasia has been described in several genetic syndromes, including focal dermal hypoplasia (FDH), microphthalmia with linear skin defects (MLS), oculocerebrocutaneous syndrome (OCCS), and terminal osseous dysplasia and pigmentary defects (TODP). All but OCCS have been reported to follow an X-linked inheritance pattern. We describe a 14-year-old girl with clinical features overlapping with these disorders. She had mild mental retardation, macrocephaly, microphthalmia, right-sided morning glory optic disc anomaly, palmar and lip pits, and polysyndactyly. A swirling pattern of skin hypopigmentation, papular hypopigmented and herniated skin lesions reminiscent of FDH most prominent over her face, head, hands, and feet was evident. Brain magnetic resonance imaging (MRI) showed polymicrogyria (most severely in the perisylvian and mesial frontal regions), enlarged left lateral ventricle, partial agenesis of the corpus callosum, and optic nerve tumor on the right. Dermatopathologic examination of the skin lesions was consistent with basaloid follicular hamartomas. The skin and digit anomalies observed overlap with FDH, but polymicrogyria, basaloid follicular hamartomas, optic nerve tumor, and morning glory anomaly have not previously been described in FDH. Skin defects in MLS are linear and the eyes typically have sclerocornea. Polymicrogyria has been described in OCCS, but not in any of the other three syndromes. The limb anomalies in TODP are reductions rather than polysyndactyly. Skin defects are localized to the face, and digital fibromas usually occur. While significant overlap exists between all four of the syndromes discussed, we believe that the constellation of anomalies observed in this girl most likely comprises a newly recognized syndrome.

Encephalocraniocutaneous lipomatosis: a neurocutaneous syndrome