LINEAR NEVUS SEBACEOUS SYNDROME: REPORT OF TWO CASES AND A REVIEW OF THE LITERATURE

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382

LINEAR

NEVUS

SEBACEOUS

SYNDROME:

REPORT

OF TWO

CASES

AND

A REVIEW

OF THE

LITERATURE

Frederick H. Lovejoy, Jr., M.D., and William E. Boyle, Jr., M.D.

From the Department of Medicine, Children’s Hospital Medical Center, and the Department of

Pediat-rics, Harvard Medical School, Boston, Massachusetts

ABSTRAC.F. Two cases of linear nevus sebaceous

syndrome are described and a review of the eleven cases now reported in the literature is un-dertaken.

The first patient has retardation, seizures, and classic ectodermal lesions while the second patient manifests typical cutaneous lesions and only an

E

CTODERMAL defects which are present at

birth

may or may not be associated with

concomitant neurologic disease. There is a

gradually increasing list of syndromes of

neuroectodermal dysplasia, all of which

show distinctive ectodermal lesions as well

as neurologic impairment.’ To date, these

syndromes include neurofibromatosis (von

Recklinghausen’s disease),

trigeminoence-halo-angiomatosis (Sturge-Weber

dis-ease), tuberous sclerosis, Lindau-von

Hippel disease, and ataxia telangiectasia.

These syndromes may be present as mixed

or incomplete entities, and within one

syndrome, there may be a wide spectrum

of disease.

In 1962 Feuerstein and Mims2 described

two cases in which there was a linear

mid-line nevus sebaceous associated with

men-tal retardation and seizures. They felt these

cases represented a new syndrome of

neuro-ectodermal dysplasia and proposed early

de-fective embryogenesis in primordial

ecto-derm as a possible etiology. During the past

six years we have had the occasion to

fol-low two patients with the linear nevus

sebaceous syndrome.

CASE REPORTS

Case 1 (CHMC 59-80-59)

C. R. was first admitted as a 2-month-old male

elevated cerebrospinal fluid protein as evidence of

neurologic disease. The rationale for defining the

syndrome as an entity distinct from other neuro-cutaneous syndromes is discussed and a pleo-morphic presentation of the syndrome is suggested.

Pediatrics, 52:382, 1973, NEVUS, LINEAR NEWS SEBACEOUS SYNDROME.

infant with recurrent apneic spells. These occurred suddenly, without relation to feeding or excitement and were characterized by an initial grunt followed by increasing blueness lasting 15 seconds to one minute. The spells usually ended with a sudden cry and mild postical sleep. The family history revealed that a maternal great aunt had seizures of unknown type. There was no family history of retardation nor of skin disease.

Examination revealed a robust, 2-month-old

male in the 90th to 97th percentile for height and weight. There were three smooth, small, discrete, yellow papules located in the midline of the nasal columella in a linear distribution. Extending from the lower lip to below the tip of the chin there was a linear yellow plaque composed of many finely umbilicated papules. There was a large oval irregularly pitted plaque on the right cheek. On the buccal surface of the mouth, there were multiple small, white, ill-defined papules (Fig. 1). Neurological assessment and the rest of the physi-cal examination were normal for age. Blood chem-istries including calcium, phosphorous, fasting blood glucose, cholesterol, phospholipids, and serum electrophoresis were normal. A lumbar punc-ture was normal. An electrocardiogram, brain scan,

and pneumoencephalogram were all normal. The

first two electroencephalograms were normal, but

subsequently changed at 33 months of age to show abnormal bursts of sharp waves and spikes over the right hemisphere. A biopsy specimen taken from the linear lesion under the mandible showed

normal stratified epithelium and a considerably increased number of sebaceous glands consistent with linear nevus sebaceous.

He continued to have apneic spells resistant to treatment with diphenyihydantoin (Dilantin) and

sodium phenobarbital. At 43 months of age the

(Received January 17; revision accepted for publication March 9, 1973.)

ADDRESS FOR REPRINTS: (F.H.L., Jr.) Children’s Hospital Medical Center, 300 Longwood Ave-nue, Boston, Massachusetts 02115

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383

apneic spells ceased and were replaced by infantile

mvoclonic spasms, and his electroencephalogram

revealed a diffusely disorganized hypsarrhythmic

tracing with discharges now distributed bilaterally. At 5 months of age the infant did not roll over, could lift his head only from the prone position, and would not reach for or grasp objects.

The patient has been seen at frequent intervals and is severely retarded. He stands only with sup-port, has no speech, and is unable to feed or dress himself. He is hypotonic with markedly decreased reflexes.

Seizures have persisted and have been

particu-larly difficult to control. Multiple EEGs have

shown diffuse disorganization with irregular

poly-spikes, slow wave complexes, and poor background development. During a five-year period no clinical or laboratory evidence (EEGs, Sonar B scans, technetium scans ) for a mass lesion has devel-oped. Lumbar punctures and skull x-rays have remained normal. The facial lesions have become less prominent with time, losing their bright orange appearance and appearing to regress in size.

CASE 2 (CHMC 60-37-37)

T. C. has been followed since 2 months of age because of verrucous midline facial lesions which simulated both case 1 as well as cases previously reported in the literature. The lesions had been

present since birth. The child was developing normally and was without seizures. The family history was negative for seizures. There was one case of mental retardation not associated with cu-taneous lesions on the maternal side of the family. A maternal grandmother had multiple warts and

there was a strong history of “moles” on the

paternal side of the family.

Physical examination at 5 months of age was normal save for multiple verrucous yellow-orange lesions involving the midline of the upper lip and chin and the left side of the cheek, ear, and scalp.

Alopecia existed over the area of scalp involvement.

An EEC at 5 months and a thiopental sodium (Pentothal) EEG at 8 months of age were in-terpreted as normal. A lumbar puncture at 5 months of age revealed a protein of 108.6 mg/100 ml with a normal glucose cell count, col-loidal gold, and SCOT. This was repeated at 7 months of age and was again normal save for a protein of 74.2 mg/100 ml. A biopsy of the chin lesion at 5 months of age showed numerous nor-mally formed sebacous glands.

The patient has been followed up to the present age of 63 years. He has developed normally at-taining all motor and adaptive milestones at the expected age. His mental and verbal development has been normal and has exceeded that of his sibs at a comparable age. IQ testing at 43 years

of age (Stanford-Binet, Draw-a-man, Test of

FIG. 1. Midline linear lesion on nasal columella

and chin along with right cheek and mucosal lesions at 2 months of age (case 1).

Visual Motor Integration ) showed a functioning level above average for age (IQ 105 ). Repeat IQ testing at 6 years of age was in the superior range

for age. Neurological examinations at 1, 33k, 5, and

63 years of age were normal. A repeat lumbar

puncture at 43 years of age was normal except for a persistently elevated protein of 90 mg/100 ml. A spinal tap at 63 years of age was again nor-mal save for an elevated protein of 123 mg/100 ml. The patient has been without seizures and EEC, spine and skull x-rays remain normal. The patient

is performing well above average in the first grade.

In view of his very satisfactory level of functioning and lack of abnormalities on neurological examina-tion further diagnostic studies have been deferred. With the passage of time the sebaceous lesions on the face and scalp have become less prominent

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FIG. 2. Midline verrucous yellow-orange lesions at

43 years of age (case 2).

extensive surgical procedure for the neck lesion at a later date.

DISCUSSION

Feuerstein and Mims’2 original paper has

been followed by the description of nine

additional patients, all of whom have had

the triad of linear midline sebaceous nevus,

mental retardation and seizures, plus a

va-riety of other abnormalities ectodermal and

mesodermal in

origin.3’

In addition,

Gil-us’2 notes one patient with a similar

syndrome. In one patient a partial temporal

lobectomy was performed to control seiz-ures, and pathologically the brain was said

to show “mature brain tissue with some

focal hemorrhages.” No specific cellular

abnormalities were noted.4 In the one case

in which death has occurred no pathologic

examination of the brain was perforemd.”

Dermatologists have recognized the

nevus sebaceous lesion as an entity since

1895 when Jadassohn1’ first described the

characteristic unctuous yellow nodules with

granular surfaces pitted with hypertrophic

sebaceous glands. He noted the lesions

could be localized, linear, or generalized

and were free of hair follicles. He used the

term to describe localized malformations of

some normal component of the skin, hence

the lesion of nevus sebaceous contained

excess normal sebaceous glands. They

gen-erally appeared on the face or scalp, and

were present at birth or appeared in early

childhood. The term nevus sebaceous of

J

adassohn was introduced into the

Amen-can literature in 1932,14 and the

derma-tologic literature has regularly carried

re-ports of small numbers of cases, Their

concern has been mainly the cosmetic and

the malignant potential of the lesions. In

1965 Mehregan and Pinkus15 reviewed 150

cases, and pointed out the lesion goes

through three rather distinct stages. In

stage one, lasting from birth to puberty,

the lesion is small, hairless, and may

actu-ally regress in size. At puberty, stage two,

the sebaceous glands enlarge and the

epi-dermis becomes verrucous, pitted, and

un-sightly. Stage three is the development of

secondary neoplasia (33 of 150 patients)

with the most common tumor being a basal

cell epithelioma. Thus, the nevus sebaceous

lesion is not found to be uncommon

derma-tologically.

However, the association of the

relative-ly common cutaneous lesion with central

nervous system involvement is infrequent.

The addition of our two cases brings those

reported in the literature to 13. By the

addi-tion of our second case, we have, however,

enlarged the spectrum of the syndrome.

This boy has classical cutaneous lesions

plus an elevated cerebrospinal fluid

pro-tein, but he lacks the previously noted

mental retardation and seizures. In view of

his persistent elevation of spinal fluid

pro-tein he has possible central nervous system

involvement. He does demonstrate,

how-ever, that the outlook for mental and

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385

in the presence of linear midline lesions.

As the other neurocutaneous syndromes

may have a polymorphic and frequently

incomplete presentation, it is reasonable

to postulate that the linear nevus sebaceous

syndrome may also.

Review of the literature plus our two

cases

(

Table I

)

demonstrates several points

worthy of interest:

1. The seizure pattern when present begins by the end of the first year of life (cases 1 to 12) and

includes apneic spells, myoclonic, psychomotor, Jacksonian, and grand mal seizures.

2. Retardation may range from none (case 13 ) to

severe (cases 3, 5, 6, 11, 12).

TABLE I

CASES IN LITERATURE OF LINEAR NEvus SEBACEOUS SYNDROME

Linear

Midline

Location

Other

Cutaneous

Lesions

EEG Seizure

Tipe

Age at

Onset of

Seiures

LP

Retarda-tion

Case P Nose None High voltage

spikes over #{174} temporal lobe cortex

Fluttering eyelids, chewing, cyanosis

7 weeks Normal Mild

Case 22 Forehead,

nose, upper

lip

None Spiking over

occipital

cortex

Grand ma! 4 months Normal Mild

Case 336 Nose, upper

lip, chin

Pigmented nevi: neck, trunk, cx-tremities

Abnormal Grand ma! and apneic spells

3 months Not noted Severe

Case 44 Bridge to tip of nose

None #{174}temporal

seizure focus

Jacksonian 1 year Normal Not stated

Case 55

patient 1 Forehead,

nose, upper

lip

Blue nevi and

pig-mented

nevi side of face, neck, scalp, #{174}

side of body Mixed

seizure

pattern

Major motor

5 months Normal Severe

Case 6’ Forehead Pigmented nevi-back,

#{174}arm, #{174}

leg, scalp

High voltage spikes #{174}

par-ieto-occipital

area

Grand ma! 4 months Normal Moderate-severe

Case 78 Not noted Scalp and

linear lesion #{174} cheek

Multi-focal

spikes

Infantile

spasms

5 months Norma! Present

degree not

noted

Case 8’ Nose None Abnormal Grand ma! 7 months Normal IQ:

verbal,

66; per- for-mance,

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TABLE I-(Continued)

Linear

Midline

Location

Other

Cutaneous

Lesions

EEG Seizure

Tipe

Age at

Onset of

Seiures

LP

Retarda-tion

Case 90 Midline

glabella to

tip of nose

Face, head, #{174}cheek

Hypsarrythmia Myoclonic

spasms

5 months Normal Mild

Case 10” Papules on Yellow Multi-focal Generalized 5 months Normal Death

patient 1 chest and abdomen

plaques on ear, scalp, supraorbital area.

Pig-mented

papules on

#{174}chest,

abdomen

and leg

spikes grand ma!

Case I 1” Chest and Hyperpig- Multi-focal Generalized 8 months Normal Severe patient 2 abdomen mented spikes grand ma!

veruccous lesions on neck, shoul-der, chest, abdomen

Case 12 Tip of lower lip to chin, nasal

col-umella

#{174}cheek and buccal mucosa

Sharp waves and spikes, hypsarrythmia

Apnea, in-fantile myoclonic,

grand ma!

4 months Normal Severe

Case 13 Nose, upper lip, chin

Alopecia, pigmented and blue nevi: neck, back, and chest

Normal None None Elevated

protein (74,90, 108, 123 mg/l00 ml)

Absent (IQ, 105)

3. Lumbar punctures are generally normal (

excep-tion, case 13) and in no case has the skull

x-ray shown calcification.

4. The midline location and the linear configura-lion of the sebaceous nes are common de-nominators seen in the majority of cases. In all

instances, it is present at birth. A diverse

spec-trum of additional cutaneous lesions may also be found (cases 3, 5, 6, 10, 11, 13). Alopecia is common in areas of scalp involvement (cases 3, 7, 13).

5. There has been no racial predilection. Cases have been described in an Oriental (case 5), Caucasions (cases 1, 3, 6-10, 12, 13) and Blacks (cases 2, 4, 11).

6. Cases have occurred sporadically and in both males (cases 1, 2, 7, 8, 11, 12, 13) and females

have not been described in other members of a kinship though four family trees include a history of seizures (cases 1, 5, 8, 11, 12) and two families include a history of retardation

(cases 8, 13).

7. Other abnormalities sporadically seen include

lipodermoids of the conjunctive (cases 3, 7) vascularization of the cornea and iris and choroid colobomas (cases 3, 7), hydrocephalus

(cases 3, 5) , unilateral cortical atrophy (case

7) , generalized aminoaciduria and vitamin

D-resistant rickets (case 5), coarctation of the

aorta (case 3), and ameloblastoma (case 13).

Though linear nevus sebaceous syndrome

closely resembles the other

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sug-ARTICLES

387

be separated from tuberous sclerosis to

which it bears closest similarity. First, the

cases to date have not reported

involve-ment of kidney, heart, pancreas, or bone of

a variety similar to that seen with tuberous

sclerosis. Second, adenoma sebaceum at

birth

or in early childhood is most unusual

in tuberous sclerosis.16, 17 In all 13 reported

cases of linear nevus sebaceous syndrome

cutaneous involvement has been present

at birth and has had a predilection for the

midline. In tuberous sclerosis the cutaneous

lesion is distributed most commonly

sym-metrically on the cheeks. Third, the

micro-scopic picture of the cutaneous lesions in

tuberous sclerosis is of two varieties:

Pningle type, with hyperplasia of

connec-five and vascular tissue,”’ or Balzar type,

nodular with excessive fibrosis.’ This is in

contrast to the increased number but

normal-appearing sebaceous glands seen

in linear nevus sebaceous. Thus, linear

nevus sebaceous syndrome would appear

to be an entity distinct from tuberous

sclerosis.

In previous reports the mere presence

of a midline sebaceous nevus was felt to

indicate a poor prognosis neurologically.

Patient 13 in this report, though

manifest-ing central nervous system involvement

(

elevated cerebrospinal fluid protein

)

is

without seizures and retardation. Other

pa-tients have demonstrated midline linear

nevus sebaceous lesions without any

obvi-ous neurologic impairment. 14, 15,19, 20 We

would then caution those who would feel

the mere presence of a midline sebaceous

nevus must carry with it an unhappy

neurologic prognosis.

REFERENCES

1. Holmes, L. B., Moser, H. W., Halldorsson, S., Mack, C., Pant, S. S., and Matzilevich, B.: Mental Retardation - An Atlas of Disease

with Associated Physical Abnormalities, New York: The MacMillan Company, 1972. 2. Feuerstein, R. C., and Mims, L. C.: Linear

nevus sebaceous with convulsions and mem-tal retardation. Amer. J. Dis. Child., 104: 675, 1962.

3. Marden, P. M., and Venters, H. D.: A new

neurocutaneous syndrome. Amer. J. Dis. Child., 112:79, 1966.

4. Solomon, L. NI., Fretzin, D. F., and Dewald,

R. L.: The epidermal nevus syndrome. Arch. Derm., 97:278, 1968.

5. Sugarman, C. I., and Reed, W. B. : Two

un-usual neurocutaneous disorders with facial cutaneous signs. Arch. Neurol., 21:242, 1969.

6. Monahan, R. H., Hill, C. W., and Venters,

H. D. : Multiple choristomas, convulsions, and mental retardation as a new neurocu-taneous syndrome. Amer. J. Ophthal., 64:

529, 1967.

7. Diehl, A. M., and Funderburk, S.: Picture of the Month. Amer. J. Dis. Child., 120:139, 1970.

8. Moynahan, E. J., and Wolff, 0. H.: A new

neurocutaneous syndrome (skin, eye and

brain). Brit. J. Derm. 79:651, 1967. 9. Bianchine, J.: The nevus sebaceous of

Jadas-sohn. Amer. J. Dis. Child., 120:223, 1970.

10. Herbst, B. A., and Cohen, M. E. : Linear nevus sebaceous : A neurocutaneous syndrome

as-sociated with infantile spasms. Arch. Neurol.,

24:317, 1971.

11. Lansky, L. L., Funderburk, S., Cuppage, F. E., Schimke, R. N., and Diehi, A. M.: Linear sebaceous nevus syndrome. Amer. J. Dis. Child., 123:587, 1972.

12. Gellis, S. S. : Year Book of Pediatrics. Chicago: Yearbook Medical Publishers, Inc. 1963-1964, p. 143.

13. Jadassohn, J.: Bemerkungen Zur Histologie

Der Systematisierten Naevi and Unber “Talgdrusen-Naevi.” Arch. Derm. Syph., 33:

355, 1895.

14. Robinson, S. S. : Naevus sebaceous (

Jadas-sohn). Arch. Derm. Syph., 26:663, 1932. 15. Mehregan, A. H., and Pinkus, H.: Life history

of organoid nevi. Arch. Derm., 91:574, 1965.

16. Chao, D. H. : Congenital neurocutaneous syn-dromes of children. J. Pediat., 55:447, 1959.

17. Brain, W. R., and Walton, J. N. : Brain’s

Dis-eases of Nervous System. London: Oxford University Press, 1969.

18. Butterworth, J., and Wilson, M. C.:

Dermato-logic aspects of tuberous sclerosis. Arch. Derm. Syph., 43:1, 1941.

19. Conner, A. E., and Bryan, H. : Nevus seba-ceous of Jadassohn. Amer. J. Dis. Child.,

114:628, 630, 1970.

20. MacCollum, D. W.: personal communication.

ACKNOWLEDGMENT

The authors would like to thank Dr. William

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1973;52;382

Pediatrics

Frederick H. Lovejoy, Jr. and William E. Boyle, Jr.

REVIEW OF THE LITERATURE