Linear Nevus Sebaceous Syndrome

J Med Sci 2006;26(2):077-082
http://jms.ndmctsgh.edu.tw/2602077.pdf
Copyright © 2006 JMS
Received: March 21, 2005; Revised: September 8, 2005;
Accepted: September 15, 2005.
* Corresponding author: Chuen-Ming Lee, Department of
Pediatrics, Tri-Service General Hospital, 325, Cheng-Gong
Road Section 2, Taipei 114, Taiwan, Republic of China. Tel:
+886-2-87927025; Fax: +886-2-87927293; E-mail: lcmpin
@yahoo.com.tw
Linear Nevus Sebaceous Syndrome
Cheng-Chun Chen 1 , Shao-Hung Lien 2 , Mu-Ling Hsu 2,3 , Chiung-Hsi Tien 2 , Chun-Jung Chen 2 ,
Pei-Yuan Chang 1 , and Chuen-Ming Lee 2*
Department of Pediatrics, 1 Armed Forces Sung Shan Hospital, Taipei,
2 Tri-Service General Hospital, National Defense Medical Center, Taipei,
3 Armed Forces Hualien Hospital, Hualien,
Taiwan, Republic of China
Cheng-Chun Chen, et al.
Linear nevus sebaceous syndrome is a rare, congenital neurocutaneous syndrome comprising nevus sebaceous, seizures and
mental retardation. Multiple organ system anomalies can occur. We report a male neonate with a linear-shaped nevus
sebaceous over the face and scalp, whose prenatal brain sonogram revealed dilatation of the left lateral ventricle and a cysticlike
lesion over the posterior cranial fossa. Postnatal magnetic resonance imaging of the brain showed hemimegalencephaly
ipsilateral to the nevus sebaceous. Despite no seizures occurring during hospitalization, the diagnosis was established
according to typical cutaneous lesions and brain images.
Key words: colpocephaly, hemimegalencephaly, linear nevus sebaceous syndrome, neurocutaneous syndrome
INTRODUCTION
Linear nevus sebaceous syndrome is a rare neurocutaneous
disease characterized by a midline facial skin lesion
(linear nevus sebaceous), seizures and mental retardation 1-3 .
Here, we report on a male infant with linear nevus sebaceous
syndrome, whose prenatal brain sonogram was
abnormal. Confirmation of this diagnosis was made by the
presence of typical cutaneous lesions, seizures, and brain
images after birth.
CASE REPORT
A full-term, male neonate was born to a 38-year-old
mother (gravida 4, para 3, one prior abortion) at 40 weeks
and 4 days of gestation. Amniocentesis had been performed
at 11 weeks and 2 days of gestation. The resulting
chromosome profile revealed a normal male karyotype
without other chromosomal abnormalities. However, mega
cisterna magnum and a cystic-like lesion were noted on a
prenatal brain sonogram at 28 weeks of gestation (Figs. 1A
and B). Vertex vaginal delivery was uncomplicated and
Fig. 1 (A) Prenatal brain sonogram revealing a mega cisterna
magnum. (B) Prenatal brain sonogram revealing a cystic-like
lesion, possibly a dilated lateral ventricle. (C)
Photograph of linear, well-demarcated, slightly raised,
yellowish, hairless plaques located on the left side of the
forehead, the parietal region of scalp, the face, chin,
lower lip and left ear. Shortening of the left upper eyelid
with congenital ectropion caused by two nodules over
the lateral canthus and upper eyelid is apparent. Alopecia
is present in the involved scalp.
Apgar scores were 8 at one minute and 9 at five minutes.
The newborn’s two siblings were normal and there was no
family history of neurological disease, skin disorders or
craniofacial anomalies.
The initial physical examination showed a birth weight
of 3670 g (90th centile), a head circumference of 37 cm
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Linear nevus sebaceous syndrome
(above 90th centile) and body length of 53 cm (above 90th
centile). A cutaneous abnormality of the face consisted of
linear, well-demarcated, raised, yellowish and hairless
plaques located on the left side of the forehead, the parietal
region of the scalp, the face, chin, lower lip, and left ear.
Alopecia was present in the region of the scalp involved in
the cutaneous abnormality. A similar, less well-formed
lesion was present over the midline of the neck and the
anterior chest wall (Fig. 1C). There were no other cutaneous
manifestations, such as cafe-au-lait spots or hypo- or
hyperpigmentation lesions. Ocular examination showed
left side microphthalmia, shortage of the left upper eyelid
with congenital ectropion caused by two nodules over the
lateral canthus and upper eyelid, and extraocular movement
restriction in the left eye. Otherwise, no limbal mass
or colobomas were apparent over the bilateral eyes. The
activity and muscle power of the limbs seemed normal
without obvious signs of hemiparesis.
A brain sonogram revealed a mega cisterna magnum
and ventriculomegaly that included the third and left
ventricles. Skull films showed a hypoplastic change of the
greater wing of the sphenoid bone. Echocardiography
revealed patent foramen ovale, closing ductal arteriosus,
and mild tricuspid valve regurgitation. An abdominal
sonogram showed a grade I hydronephrosis over the left
kidney. An otoacoustic emissions test revealed a hearing
impairment on the left side.
Magnetic resonance imaging (MRI) of the brain showed
asymmetrical overgrowth of the left cerebral hemisphere,
with precedence of the occipital lobe pushing the midline
toward the right side. These observations were compatible
with hemimegalencephaly, increased gray matter in the
left parahippocampus (heterotopia), and a mega cisterna
magnum. Asymmetric arrangement of the facial bones and
a downward orientation of the left orbital bone with a
relatively small orbital cavity were also evident (Fig. 2).
During hospitalization of the patient, no seizures occurred
and no medication was prescribed. A chromosome
study of peripheral blood showed a normal male karyotype.
After being evaluated by a pediatric neurologist,
ophthalmologist, dermatologist, otologist and plastic
surgeon, the patient was discharged at 11 days of age. Four
days after discharge (16 days old), he experienced his first
seizure at home. Subsequently, numerous seizures occurred
and infantile spasm was diagnosed by a pediatric
neurologist. Because anomalies of other organ systems,
particularly the eye, ear and bone, may also be involved, a
multidisciplinary approach at a medical center was recommended
to his parents.
78
Fig. 2 (A) T2-weighted magnetic resonance (MR) study with
axial plane showing asymmetrical outgrowth of the left
cerebral hemisphere with precedence of the occipital
lobe pushing the midline towards the right; this is consistent
with hemimegalencephaly. Additionally, underdevelopment
of the left operculum was noted. (B) Increased
gray matter thickness in the left parahippocampus
(heterotopia). (C) T1-weighted MR study with sagittal
plane showing a regional patulous cerebrospinal fluidfilled
space in the posterior cranial fossa, presumably the
mega cisterna magnum. (D) T1-weighted MR study with
the coronal plane showing an asymmetric facial bone and
a downward orientation of the left orbital bone with a
relative small orbital cavity.
DISCUSSION
Although Jadassohn knew the characteristic cutaneous
manifestation of linear nevus sebaceous syndrome in 1895,
Robinson introduced the term “sebaceous nevus of Jadassohn”
in 1932 4 . The syndrome was first described by
Schimmelpenning in 1957 5 , and Feuerstein and Mims in
1962 6 . Numerous subsequent reports have confirmed that
linear nevus sebaceous syndrome is frequently associated
with ocular, hearing, cardiovascular, skeletal, hepatic, and
urinary tract anomalies 7 . Linear nevus sebaceous syndrome
is the name most often used for this disorder, although
similar associations of clinical findings have been described
under the names of neuro-ocular-cutaneous
syndrome, Feuerstein-Mims syndrome, Schimmelpenning-
Feuerstein-Mims syndrome, Jadassohn syndrome, Solomon’s
epidermal nevus syndrome, and organoid nevus phakomatosis
syndrome.
The etiology of linear nevus sebaceous syndrome is still

unknown. The syndrome occurs sporadically and no genetic
or chromosomal abnormalities have been found.
Neither sex predilection nor familial occurrence or external
factors, such as drug ingestion, viral infection or
radiation during pregnancy, have been linked to this
syndrome 2 . However, mosaic dominant lethal gene mutation
is a possible explanation 8,9 .
Nevus sebaceous is estimated to occur in 0.3% of newborns
and is usually present at birth or in early childhood 7 .
It is the hallmark of this syndrome, and is characterized by
large, often linear, sharply demarcated and slightly raised
plaques, that present a waxy or pebbly surface on the skin
of the head, face and neck. The plaques may extend to the
trunk and extremities following the line of Blaschko, with
either a yellow to tan velvety appearance or a darker
verrucous look. The life history and histopathological
findings of sebaceous nevus are age-dependent 7 . During
infancy and in early childhood, sebaceous glands within
the nevus are underdeveloped or abortive and no hair
follicles are present. At puberty, the sebaceous glands
within the nevus are characterized by papillomatous epidermal
hyperplasia and a massive mature apocrine gland
deep in the dermis. After puberty, benign and malignant
tumors may develop within the nevus. These include basal
cell carcinoma (15%-20%, most common), syringocystadenoma
papilliferum, syringoma, nodular hidradenoma,
sebaceous thelioma, keratoacanthoma, and squamous cell
carcinoma. Therefore, prophylactic excision of nevus sebaceous
at or before the onset of puberty, or close monitoring,
is recommended 7,10 . Our patient had nevus sebaceous with
a linear configuration that involved the left side of the face,
the scalp, ocular region and anterior chest wall, which are
the most common sites of skin lesions in linear nevus
sebaceous syndrome. Because of his young age, sebaceous
glands within the nevus were undeveloped and no hair
follicles were present.
Associated neurological abnormalities, including seizures
and mental retardation, are common features of
linear nevus sebaceous syndrome. Seizures occur in 44%-
90% of patients during their first year of life, with mental
retardation or developmental delay occurring in 40%-80%
of patients 1 . The head may be enlarged and other associated
neurological manifestations include progressive
hemiparesis, quadriparesis, hypotonia, reflex abnormalities,
gait disorders, diencephalic syndrome, microcephaly and
macrocephaly 10,11 . A major finding with MRI is hemimegalencephaly
(or unilateral megalencephaly), which is
characterized by congenital overgrowth of one cerebral
hemisphere ipsilateral to the sebaceous nevus with an
increased volume of white matter and dilatation of the
Cheng-Chun Chen, et al.
lateral ventricle on the affected side. The affected brain has
essentially no function and is frequently clinically associated
with hemiparesis, early-onset seizures, mental retardation,
hemimacrocephaly and severe encephalopathy 7,12 . Partial
or complete hemispherectomy has been recommended in
children with intractable seizures 1 . The consistent association
of hemimegalencephaly with the sebaceous form of
epidermal nevus provides evidence that linear nevus sebaceous
syndrome is a distinct epidermal nevus syndrome.
Thus, hemimegalencephaly is a sign in neurological imaging
that may obviate the need for skin biopsy in patients
with epidermal nevi 7 . Heterotopic gray matter is likely to
be the source of a patient’s seizures, which may be the
ultimate cause of death 13 . Other common neurological
imaging findings including focal pachygyria, cortical
atrophy, hydrocephalus, porencephaly and cerebral neoplasm
have been reported 2,14,15 . In our patient, there were no
seizures during the hospitalization period; however, he
experienced numerous seizures after discharge. His intelligence
could not be evaluated because of his young age.
However, hemimegalencephaly, colpocephaly 16 , regional
increased gray matter thickness, and heterotopia in the left
parahippocampus, were evident upon MRI. According to
the characteristic skin lesions, seizures, and these neurological
findings, the diagnosis of linear nevus sebaceous
syndrome was made.
Ocular abnormalities are another clinical manifestation
that occur in about half of patients with linear nevus
sebaceous syndrome 3,10 . Indeed, it has been suggested that
the syndrome could be considered an oculo-neuro-cutaneous
syndrome, and ocular abnormalities should be included
in the diagnostic triad 17 . The most common ocular
lesions are choristoma of conjunctiva, coloboma of the globe
or lid, retinal abnormalities such as optic nerve hypoplasia,
pseudopapilledema, microphthalmia or macrophthalmia,
corneal opacities and exotropia/esotropia 7,10 . Mechanisms
of visual loss include visual inattention due to intractable
seizures, subcortical visual loss secondary to unilateral
hypoplasia of an optic radiation associated with hemimegalencephaly,
dysplasia of the optic disc and peripapillary
sclera, and visual occlusion from a corneal opacification
adjacent to a limbal dermoid 7 . In our patient, left side
microphthalmia and hemimegalencephaly were present.
Accordingly, the prognosis of visual function was poor
despite surgical treatment being conducted twice to rectify
his left eyeball.
Other anomalies have also been documented in linear
nevus sebaceous syndrome 10,18 . In the cardiac system,
these include ventricular septal defects, coarctation of the
aorta, patent ductus arteriosus, hypoplastic left heart, su-
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Linear nevus sebaceous syndrome
praventricular tachycardia, and pulmonary stenosis.
Anomalies in the urogenital system include renal cystic
dysplasia, double collecting system, cryptorchidism, inguinal
hernia, hypospadias, micropenis, testicular and
paratesticular tumors. Skeletal involvement has been
documented 19 , including skull, facial or orbital bone
deformities, limb deformities, scoliosis, kyphosis, and
hypophosphatemic vitamin D-resistant rickets 20 . Furthermore,
an inner ear malformation with impairment of hearing
function has been described in a patient with linear
nevus sebaceous syndrome. In our patient, facial or orbital
bone deformities were found and otoacoustic emission
screening showed an abnormal finding over the left ear.
Further audiological examination of the patient was suggested
to his family by an attending otologist.
Additionally, developmental delay was observed in our
patient and mental retardation was highly suspected, despite
a measure of intelligence not being obtained because
of his young age. Ataxic gait manifested when he was
walking and dysarthria was present in his speech, which
might be due to the involvement of the cerebellum.
In a review of the literature, we found a report of a single
case of linear nevus sebaceous syndrome displaying an
abnormal intrauterine sonography at 18 weeks of gestation,
in which the major finding was a right side intracranial
cyst 1 . In another case, prenatal detection of echogenic softtissue
structures external to the cranium and face was
reported, along with the detection of hydrocephalus, intrathoracic
mass and ascites by sonogram 21 . Nowaczyk et
al. demonstrated antenatal progression of intracranial abnormalities
in encephalocraniocutaneous lipomatosis by
prenatal sonogram, and emphasized the difficulty with
antenatal diagnosis of hamartoneoplastic conditions based
on sonographic evaluation 22 . These authors considered
that other modalities, such as MRI or three-dimensional
sonogram, could be useful for prenatal diagnosis. Our
patient received a prenatal sonogram at 28 weeks of
gestation. The diagnosis was not established until birth,
although several abnormal findings had been found
prenatally.
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