Oculo-ectodermal syndrome: A case report and further delineation of the syndrome

Oculo-ectodermal syndrome (OES - OMIM 600628), also known as Toriello Lacassie Droste syndrome, is a very rare condition, first described by Toriello et al., in 1993. OES has been proposed to be a mild variant of encephalocraniocutaneous lipomatosis (ECCL). It is characterized by aplasia cutis congenita (ACC), epibulbar dermoids, coarctation of the aorta, arachnoid cysts in the brain, seizure disorder, hyperpigmented nevi, non-ossifying fibromas and a predisposition to develop giant cell tumors of the jaw. There are few reported cases of OES worldwide but with no definite diagnostic criteria yet. We present a case in a child with unilateral hyperpigmented nevi and ACC on the scalp, ocular lesions (lipodermoid cysts and coloboma), temporal arachnoid cyst, spinal lipomatosis and aortic coarctation with the aim of enhancing the foundation to establish diagnostic criteria for this condition. It additionally serves as a teaching point to emphasize the importance of pursuing a definite diagnosis when faced with such a multisystem illness, to counsel patients and their parents regarding long term morbidity and overall prognosis.


INTRODUCTION
Oculo-ectodermal syndrome (OES, OMIM 600268), was first described by Toriello et al., in 1993 1 and is characterized by aplasia cutis congenita (ACC), epibulbar dermoids, coarctation of the aorta, arachnoid cysts in the brain, seizure disorder, hyperpigmented nevi, non-ossifying fibromas and a predisposition to develop giant cell tumors of the jaw. Vascular anomalies predisposing to occlusive  12 The authors recommend further testing of patients with OES and ECCL to see whether this mutation was unique to their case or could actually be the genetic cause for the similar neurocutaneous anomalies seen with OES and ECCL. The possibility of autosomal recessive inheritance was mentioned in a case with a severe phenotype where there was consanguinity between parents. 11 However, more recent literature have implicated various possibilities, including that of a mutation of a tumor suppressor gene 7 and a genetic defect in a transcription factor controlling ocular development. 9

CASE REPORT
We report a 7-year-old Egyptian boy, the second child of non-consanguineous parents with an older child having autistic disorder of unknown origin. He was the product of full term uncomplicated pregnancy, born by LSCS due to previous caesarean section. His birth weight was 3.2 kg and he had achieved all milestones appropriately. There was no history of neurocutaneous or seizure disorders in the family. According to parents, the child was born with "right eye lesions", patchy areas of alopecia in the scalp, and skin lesions as described below. The eye lesions were diagnosed as a coloboma and epibulbar dermoid involving the right eye, but no definitive treatment was carried out at the time.
At the age of eighteen months, the child developed febrile status epilepticus and at 20 months afebrile focal clonic seizures which involved the right side. Seizures were treated with Levetiracetam and Carbamazepine. With the constellation of his congenital eye anomalies, skin lesions and seizures, the possibility of having a neurocutaneous disorder such as Epidermal Nevus syndrome or Goldenhar syndrome was raised with the parents. However, no definite diagnosis was made and the family had relocated to Qatar when the child was 6 years old. It was during one of his pediatric emergency visits in Doha, for a viral illness that the child was noted to have hypertension. Detailed scrutiny of his medical reports revealed that the child did have elevated blood pressure measurements which were in the range of 140-180 systolic and 75-100 diastolic at the age of 3 years. He was admitted to our institution at the age of 7 years for investigating the cause of his hypertension; which did indeed reveal a previously undetected, long segment coarctation of the descending aorta. This was medically managed by the pediatric cardiology team. Our pediatric neurology team was consulted for follow up of his epilepsy which was under good control at the time. Given the existing constellation of signs and symptoms, we performed a thorough literature search and tried putting the different parts of the puzzle into place to arrive at a conclusive diagnosis to counsel the family regarding long term morbidity and prognosis.

Physical examination
Upon presentation at the age of 7 years, his weight was 22 kg (25 th percentile) and height was 116 cm (25 th percentile). The child was alert and hyperactive.
The following features were observed:

Skin
Hyperpigmented skin lesions exclusively on the left side of the body of variable sizes, extending over the nape of the neck (Figure 1), the left axilla with verrucal changes (Figure 2) and downward to the trunk and abdomen till the level of the umbilicus, anteriorly and posteriorly. A hypopigmented area was present over the lateral aspect of the left thigh. Three areas of congenital alopecia were noted, two over the right temporal area and another over the vertex of the scalp measuring 6(5 cm. These were clinically diagnosed as Aplasia Cutis Congenita (ACC), although no biopsy was taken ( Figure 3).

Ocular examination
Right eye examination showed congenital right-sided coloboma of the eyelid, strabismus with amblyopia and dermolipoma with a limbal dermoid at the  superolateral limbus, extending over the cornea covering part of the visual axis ( Figure 4). He was only able to count fingers at 3 meters which improved to 6/6 with glasses. Retinal structure and intraocular pressure were normal. The left eye was normal. The rest of the systemic and neurological examinations were normal. There was no evidence of non-ossifying fibromas involving the long bones.
Echocardiography: revealed long segment coarctation of the descending aorta measuring 2 cm with a pressure gradient of 25 mm Hg at the thoracic aorta and gradient of 40 mm Hg at the abdominal aorta.
CT angiogram: of the abdomen revealed a 3.5 cm long segment descending and pre-renal aortic coarctation, which was 6 mm in largest diameter ( Figure 5). An interesting finding in the CXR was the absence of rib notching that is usually seen in aortic coarctation.
Brain and orbit MRI: revealed a right temporal pole extra-axial arachnoid cyst causing mass effect on the right temporal lobe ( Figure 6). There was neither intraorbital extension of the dermolipoma nor any intracranial lipomas; however, absence of the right lacrimal gland was noted ( Figure 5). MRI of the spine revealed posterior intra-spinal and intra-dural lipomas extending along the cervico-dorso-lumbar levels the largest at the cervico-dorsal region, indenting the dorsal spinal cord ( Figure 6). A diagnosis of oculo-ectodermal syndrome was made based on findings of ACC, epibulbar dermoids, coarctation of the aorta, arachnoid cysts in the brain, seizure disorder and hyperpigmented nevi in the patient. 3 Genetic test results are still awaited, and whole genome sequencing was proposed to the family with the intention of identifying an affected gene, which was still being considered at the time of writing this article. Our case is the eighteenth case of OES to be reported in literature.

DISCUSSION
Oculo-ectodermal syndrome is a very rare, neurodevelopmental syndrome with multisystem involvement (eye, skin, CNS and cardiovascular). The genetic basis has not been fully understood yet, however, Toriello 1 suggested that a new dominant mutation is possible, and Fickie et al., 12 4 The absence of the lacrimal duct in our patient has not been reported as part of this syndrome as far as we are aware. We suggest that brain and spinal MRI with angiography should be performed in all patients with suspected OES or ECCL to rule out intra-and extracranial lipomatosis and abnormalities of cerebral vessel structure like Moyamoya disease which would put such patients at an increased susceptibility for strokes thereby making it one of the main risk factors for increased morbidity and mortality. 3 We also recommend serial follow-ups by a pediatric dentist and orthopedic surgeon as these children are prone to develop tumours involving the jaw and long bones, even at a young age. 12 It is likely that with further clinical genetic understanding, this syndrome will become better delineated and that it may be a spectrum of severity in the phenotype of a single genetic disorder.