History
The clinical picture of Haberland syndrome may vary from patient to patient; however, a set of clinical features is regarded as characteristic for the disorder. [13] The primary clinical features noted for almost all cases are as follows:
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Unilateral porencephalic cysts with cortical atrophy
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Intracranial lipomas, often located in the cerebellopontine angle
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Ipsilateral connective tissue usually lipomatous hamartomas of the scalp, eyelid, and outer globe of the eye (bilateral eye involvement in 1 report) [14]
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Cranial asymmetry
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Marked developmental delay and mental retardation
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Seizures
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Spasticity of the contralateral limbs
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Unilateral odontomas (1 report) [15]
The diagnosis of encephalocraniocutaneous lipomatosis (ECCL) is mainly based on history, clinical examination, and imaging studies. Original diagnostic criteria were published by Hunter in 2006. In 2009 Moog has analyzed 54 patients with encephalocraniocutaneous lipomatosis and proposed revised diagnostic criteria. [16]
Table. Revised Diagnostic Criteria for Encephalocraniocutaneous Lipomatosis [16] (Open Table in a new window)
Eye |
Skin |
Central Nervous System |
Other |
Major criteria |
Major criteria |
Major criteria |
Major criteria |
Choristoma, with or without associated anomalies |
Proven nevus psiloliparis (NP) |
Intracranial lipoma |
Jaw tumor (osteoma, odontoma, or ossifying fibroma) |
Possible NP and >1 of minor criteria 2-5 |
Inraspinal lipoma |
Multiple bone cysts |
|
>2 of minor criteria 2–5 |
>2 of minor criteria |
Aortic coarctation |
|
Minor criteria |
Minor criteria |
Minor criteria |
|
Corneal and other anterior chamber anomalies |
Possible NP |
Abnormal intracranial vessels (eg, angioma, excessive vessels) |
|
Ocular or eyelid coloboma |
Patchy or streaky nonscarring alopecia (without fatty nevus) |
Arachnoid cyst or other abnormality of meninges |
|
Calcification of globe |
Subcutaneous lipoma(s) in frontotemporal region |
Complete or partial atrophy of a hemisphere |
|
Focal skin aplasia/hypoplasia on scalp |
Porencephalic cyst(s) |
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Small nodular skin tags on eyelids or between outer and tragus canthus |
Asymmetrically dilated ventricles or hydrocephalus |
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Calcification (not basal ganglia) |
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Application of the Criteria to the Diagnosis of Encephalocraniocutaneous Lipomatosis |
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Definite case |
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Three systems involved, major criteria in >2, or |
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Three systems involved, proven NP or possible NP + >1 of minor skin criteria 2–5 |
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Two systems involved with major criteria, one of which is proven NP or possible NP >1 of minor skin criteria 2-5 |
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Probable case |
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Two systems involved, major criteria in both |
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Two systems involved, proven or possible NP |
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Physical Examination
The characteristic cutaneous neoplasm, named nevus psiloliparus (Greek for hairless fatty nevus), has been noted so far only in patients with encephalocraniocutaneous lipomatosis (ECCL). [17] In 2004, Happle and Horster reported nevus psiloliparus in 2 otherwise healthy girls, suggesting that the skin lesion may be a nonsyndromic skin disorder [18] ; however, it still remains a characteristic change for encephalocraniocutaneous lipomatosis. Large, slightly protuberant, soft tissue masses of the scalp are located on one side of the scalp and usually do not cross the midline, but bilateral involvement also has been reported. These cutaneous soft tumors, often lipomas, have overlying skin devoid of hair.
Alopecia is a constant finding. [19]
Cutaneous abnormalities usually involve only the head and face; however, they may be documented soon after birth. [20]
Some patients have ill-defined bony protuberances on the skull (associated with the scalp), subcutaneous lipomatous nodules, and tumors. Note the image below.
A child with Haberland syndrome. Apparent alopecia and small cutaneous soft lipomas on the face and eyelid.
Skin-colored papular or polypoid cutaneous nodules may be observed on the face and eyelid in a unilateral distribution on the same side as the scalp lesions. These may represent small angiolipomas, fibrolipomas, connective tissue nevi, or mixed hamartomas of cartilage, fat, and connective tissue. Mandibular osteomas have also been reported.
Pigmented melanocytic nevi are another skin abnormality found in some patients with encephalocraniocutaneous lipomatosis.
Ocular involvements appear to be a uniform feature of Haberland syndrome. The most common ocular abnormalities include epibulbar choristomas, small papules around the eyelids, and desmoid tumors of the scleral limb. Persistent hyaloid vessels, dislocation of the lens capsule, clouding of the cornea, iris dysplasia, colobomas, microphthalmia, ocular calcifications, and optic nerve pallor also have been reported. Ocular manifestations may be bilateral. Almer et al reported a case of encephalocraniocutaneous lipomatosis with bilateral aniridia. [21] Valladares et al described a patient (a full-term newborn) with bilateral conjunctival tumors. [22]
Neurological manifestations occur to variable degrees. Mental status of the reported cases varies from totally normal to severe mental retardation. Seizures also are not a constant feature and may become evident in some patients in the first year of life, leading to mental retardation (only in adolescence in others). In most patients, testing of intellectual function revealed IQ scores ranging from 65-75. Spasticity, hemiplegia, and facial paresis also have been described in patients with encephalocraniocutaneous lipomatosis. One patient, delineated by Fishman in 1987, developed a subarachnoid hemorrhage, presumably related to leakage of blood from an aneurysmal-type vascular malformation. [23]
Other abnormalities found on physical examination of patients with encephalocraniocutaneous lipomatosis include vertebral abnormalities, extradural spinal cord lipomatous lesions, or leg, arm, or chest asymmetry. Thakur et al present a case of a patient with a large temporal exostosis. [24] Pregowska et al report an infant with multifocal atrial tachycardia. [25] Moog also found congenital heart malformations in five of 54 analyzed patients, in particular aortic coarctation (4 of 5). [16]
Some authors have recognized similarities in the clinical picture of encephalocraniocutaneous lipomatosis and oculocerebrocutaneous lipomatosis (Delleman syndrome). Hunter compared the clinical picture of both syndromes (40 patients with Delleman syndrome and 44 with encephalocraniocutaneous lipomatosis) but the correlation remains unclear. [26]
Some authors also propose oculoectodermal syndrome as a milder variant of encephalocraniocutaneous lipomatosis, without intracranial lipomatosis. [27]
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A child with Haberland syndrome. Apparent alopecia and small cutaneous soft lipomas on the face and eyelid.
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CT scan shows an enlargement of the left lateral ventricle in a child with Haberland syndrome. Note an asymmetry of the hemispheres and calcifications in the midline.
Tables
Eye |
Skin |
Central Nervous System |
Other |
Major criteria |
Major criteria |
Major criteria |
Major criteria |
Choristoma, with or without associated anomalies |
Proven nevus psiloliparis (NP) |
Intracranial lipoma |
Jaw tumor (osteoma, odontoma, or ossifying fibroma) |
Possible NP and >1 of minor criteria 2-5 |
Inraspinal lipoma |
Multiple bone cysts |
|
>2 of minor criteria 2–5 |
>2 of minor criteria |
Aortic coarctation |
|
Minor criteria |
Minor criteria |
Minor criteria |
|
Corneal and other anterior chamber anomalies |
Possible NP |
Abnormal intracranial vessels (eg, angioma, excessive vessels) |
|
Ocular or eyelid coloboma |
Patchy or streaky nonscarring alopecia (without fatty nevus) |
Arachnoid cyst or other abnormality of meninges |
|
Calcification of globe |
Subcutaneous lipoma(s) in frontotemporal region |
Complete or partial atrophy of a hemisphere |
|
Focal skin aplasia/hypoplasia on scalp |
Porencephalic cyst(s) |
||
Small nodular skin tags on eyelids or between outer and tragus canthus |
Asymmetrically dilated ventricles or hydrocephalus |
||
Calcification (not basal ganglia) |
|||
Application of the Criteria to the Diagnosis of Encephalocraniocutaneous Lipomatosis |
|||
Definite case |
|||
Three systems involved, major criteria in >2, or |
|||
Three systems involved, proven NP or possible NP + >1 of minor skin criteria 2–5 |
|||
Two systems involved with major criteria, one of which is proven NP or possible NP >1 of minor skin criteria 2-5 |
|||
Probable case |
|||
Two systems involved, major criteria in both |
|||
Two systems involved, proven or possible NP |
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