PERIODIC HYPERSOMNIA, CONGENITAL ECTODERMAL
DISORDERS AND MULTIPLE EXOSTOSIS
RUBENS REIMÃO * — ARON DIAMENT **
S U M M A R Y — A c a s e o f p e r i o d i c h y p e r s o m n i a i n a n 1 1 - y e a r - o l d f e m a l e w i t h t h e u n i q u e f e a t u r e s o f m e n t a l d e f i c i e n c y , i n c o n t i n e n t i a p i g m e n t i , a c a n t h o s i s n i g r i c a n s a n d h e r e d i t a r y m u l t i p l e e x o s t o s i s ( d i a p h y s i a l a c l a s i s ) i s r e p o r t e d . T h e c l i n i c a l , P o l y s o m n o g r a p h i c a n d M u l t i p l e S l e e p L a t e n c y t e s t f e a t u r e s o f t h i s c a s e w i t h a f o l l o w u p o f s e v e n y e a r s a r e c o n s i s t e n t w i t h a d i a g n o s i s o f p e r i o d i c ( i n t e r m i t t e n t ) e x c e s s i v e s o m n o l e n c e . T h e u n i q u e p r e s e n t a t i o n , h o w e v e r , d o e s d i f f e r f r o m K l e i n e - L e v i n s y n d r o m e a n d s u g g e s t s a r e l a t i o n s h i p b e t w e e n t h e p r e d o m i n a n t l y e c t o d e r m a l , c o n g e n i t a l d i s o r d e r s a n d t h e s l e e p - w a k e , p a t t e r n d y s f u n c t i o n .
Hipersônia periódica, malformações ectodérmicas e exostose múltipla.
R E S U M O — R e l a t a - s e u m c a s o d e s o n o l ê n c i a e x c e s s i v a p e r i ó d i c a a c o m p a n h a d a d e h i p e r f a g i a , c o m i n í c i o n a s e g u n d a d é c a d a , d o c u m e n t a d o c l i n i c a m e n t e , e m t r a g a d o s p o l i s s o n o g r á f i c o s d e n o i t e i n t e i r a e n o t e s t e d a s L a t ê n c i a s M ú l t i p l a s d o S o n o . A p r e s e n t a c a r a c t e r í s t i c a s q u e o d i s t i n g u e m d a s í n d r o m e d e K l e i n e - L e v i n , a s a b e r , a o c o r r ê n c i a n o s e x o f e m i n i n o , d e f i c i ê n c i a m e n t a l , i n c o n t i n ê n c i a p i g m e n t a r , a c a n t o s e n i g r i c a n s e e x o s t o s e m ú l t i p l a .
There are two well defined syndromes of periodic hypersomnia!: menstrual
cycle-related somnolence and the Kleine-Levin syndrome ( K L S ) . The former is usually
temporally linked with the menses; the latter, a rare condition, is generally limited
to males in which the first episode of excessive sleepiness occurs in the second decade
of life associated with hyperphagia. It supposedly results from hypothalamic or lymbic
dysfunctions.
This report describes a case of periodic hypersomnia and hyperphagia, beginning
in the second decade but clearly distinct from KLS, occurring in a female with mental
deficiency, incontinentia pigmenti and multiple exostosis.
C A S E R E P O R T
M R S , a n 1 1 - y e a r - o l d f e m a l e w a s r e f e r r e d t o o u r c l i n i c s e v e n y e a r s a g o , p r e s e n t i n g
p e r i o d s o f o n e t o t w o w e e k s h y p e r s o m n o l e n c e t h a t s t a r t e d 6 m o n t h s p r e v i o u s l y . D u r i n g
t h e s e p e r i o d s , t h e p a t i e n t s l e p t m o s t o f t h e d a y a n d n i g h t , w a k i n g o n l y f o r t o i l e t n e c e s s i t i e s
a n d e a t i n g d u r i n g w h i c h t i m e s l e e p i n e s s w a s s t i l l r e p o r t e d . I n s o m e o f t h e s e p e r i o d s s h e
e x h i b i t e d v o r a c i o u s e a t i n g b u t n o i n a p p r o p r i a t e s e x u a l b e h a v i o r . S h e h a s b e e n f o l l o w e d
u p f o r 7 y e a r s a n d t h e p e r i o d s o f h y p e r s o m n o l e n c e f i r s t n o t e d e v e r y 3 t o 4 m o n t h s a r e
n o w s e e n o n l y y e a r l y . O u t s i d e t h e s e p e r i o d s s h e h a s a d e q u a t e s l e e p . T h e r e i s n o r e l a t i o n
b e t w e e n h y p e r s o m n o l e n c e a n d m e n s t r u a l c y c l e . H e r m e n s e s a r e i r r e g u l a r w i t h i n t e r v a l s
P e d i a t r i c N e u r o l o g y U n i t ( * A s s i s t a n t ; * * H e a d ) , D e p a r t m e n t o f N e u r o l o g y , F a c u l t y o f M e d i c i n e , U n i v e r s i t y o f S ã o P a u l o , a n d S l e e p D i s o r d e r s C e n t e r , A l b e r t E i n s t e i n H o s p i t a l , S ã o P a u l o .
u p t o 6 m o n t h s . T h e r e i s c o n s a n g u i n i t y i n t h e f a m i l y a n d h e r g r a n d f a t h e r h a d s i m i l a r
e x o s t o s i s . T h e p h y s i c a l e x a m i n a t i o n r e v e a l e d i n c o n t i n e n t i a p i g m e n t i w i t h a r e a s o f h y p e r
-p i g m e n t a t i o n o n t h e 4 l i m b s a n d b a c k . A c a n t h o s i s n i g r i c a n s a r o u n d t h e n o s e . E x t e n t i o n o f
t h e l e t t e l b o w l i m i t e d . N e u r o l o g i c a l e x a m i n a t i o n r e v e a l e d m e n t a l d e f i c i e n c y w i t h n o f o c a l
s i g n s . F u n d u s w a s n o r m a l . P s y c h o l o g i c a l e x a m i n a t i o n p e r f o r m e d t w i c e c o n f i r m e d I Q • = 5 5 ;
n o s y m p t o m s o f d e p r e s s i o n . E E G , C T b r a i n s c a n , b r a i n n u c l e a r m a g n e t i c r e s s o n a n c e a n d
C S F w e r e n o r m a l . C h r o m o s s o m a l s t u d y r e v e a l e d n o r m a l 4 6 X X w i t h n o r m a l b a n d s . D e r m a
-t o g l y p h i c s -t u d y w a s a b n o r m a l w i -t h T R C = 3 3 ; R — a -t d — 5 4 &l-t; - ; R w — 3 2 % ; L — a -t d — 4 9 * ;
R w = 2 8 . 4 % . R a d i o l o g i c a l e x a m i n a t i o n s s h o w e d m u l t i p l e , b i l a t e r a l e x o s t o s i s o n t h e m e t a p h y s i s
o f t h e d i s t a l f e m u r , p r o x i m a l t i b i a , d i s t a l l e f t f i b u l a , p r o x i m a l r i g h t h u m e r u s . T h e u l n a s
w e r e s h o r t . L e f t e l b o w w a s d i s l o c a t e d . H a n d X - r a y s s h o w e d d i s p l a s i a o f t h e p i s i f o r m
b o n e . B o n e a g e w a s 1 6 y e a r s f o r a c h r o n o l o g i c a l a g e o f 1 4 . S k u l l f i l m s w e r e n o r m a l . T w o
s k i n b i o p s i e s c o n f i r m e d t h e d i a g n o s i s o f i n c o n t i n e n t i a p i g m e n t i a n d a c a n t h o s i s n i g r i c a n s .
M u s c l e b i o p s y w a s n o r m a l . L a b o r a t o r y t e s t s including s e r u m c a l c i u m a n d p h o s p h o r u s , f a s t i n g
m o r n i n g blood glucose, T 3 , T 4 , T S H , F S H , a n d Cortisol w e r e n o r m a l . A l k a l i n e p h o s p h a t a s e
w a s repeatedly elevated, f r o m 5 2 2 t o 7 7 0 U / l ( n o r m a l values 6 0 - 2 2 0 U / l ) . U r i n a r y s c r e e n i n g
t e s t s f o r i n b o r n e r r o r s of m e t a b o l i s m w e r e n e g a t i v e . P e l v i c u l t r a s o u n d e x a m i n a t i o n r e v e a l e d
h y p o p l a s t i c u t e r u s a n d n o r m a l o v a r i e s .
T w o a l l - n i g h t p o l y s o m n o g r a p h i c ( P S G ) r e c o r d i n g s w e r e p e r f o r m e d ( T a b l e 1 ) u s i n g
s t a n d a r d c r i t e r i a (is) i n c l u d i n g E E G , e l e c t r o o c u l o g r a m , s u b m e n t a l a n d a n t e r i o r t i b i a l i s e l e c t r o
m y o g r a p h y , n a s a l a n d b u c c a l t h e r m i s t o r s , p n e u m o g r a m a n d e l e c t r o c a r d i o g r a m . T h e m o n i t o r i n g
w a s p e r f o r m e d i n p e r i o d s w i t h a n d w i t h o u t e x c e s s i v e d a y t i m e s o m n o l e n c e ; b o t h f a i l e d t o
s h o w b r e a t h i n g o r h e a r t r a t e a b n o r m a l i t y , o r n o c t u r n a l m y o c l o n u s . T h e M u l t i p l e . S l e e p
L a t e n c y t e s t ( M L S T ) w a s p e r f o r m e d t w i c e a c c o r d i n g t o s t a n d a r d c r i t e r i a ( J 3 ) . D u r i n g a
p e r i o d o f b a s a l n o n - h y p e r s o m n i a , m e a n s l e e p l a t e n c y w a s 1 6 . 2 m i n w i t h n o R E M s l e e p
d e t e c t e d . D u r i n g a p e r i o d o f h y p e r s o m n i a , m e a n s l e e p l a t e n c y w a s 4 . 1 m i n ; n o R E M s l e e p
d e t e c t e d .
D S N D S
T o t a l t i m e i n b e d ( m i n ) 4 2 6 3 8 5
T o t a l s l e e p t i m e ( m i n ) 4 1 2 3 2 6
S l e e p e f f i c i e n c y ( % ) 9 6 . 7 8 4 . 6
S l e e p l a t e n c y ( m i n ) 4 3
R E M l a t e n c y ( m i n ) 1 2 4 1 3 5
S t a g e 1
(%)
3 . 1 3 . 9S t a g e 2
(%)
2 8 . 9 3 9 . 8S t a g e 3
(.%)
1 2 . 3 8 . 8S t a g e 4
(%)
4 2 . 6 3 5 . 8S t a g e R E M ( % ) 1 3 . 1 1 1 . 3
Table 1 — All-night polysomnographic data obtained during baseline non-excessive daytime
somnolence period (NDS) and during a period with excessive daytime somnolence (DS).
C O M M E N T S
Incontinentia pigmenti, or Bloch-Sulzberger syndrome, occurs almost exclusively
in females and is accompanied by a wide range of ectodermal and mesodermal defects
in two thirds of the patients. Among these, mental deficiency may be found. Acan
thosis nigricans, another rare dermatosis, is characterized by hyperpigmentation and
epidermic hypertrophy. Its juvenile form may be associated with several metabolic,
endocrine or developmental abnormalities. It may occur in association with mental
deficiency and hypothalamic or pituitary endocrinopathies. In few cases, a familial
occurrence is encountered suggesting hereditary factors of still undetermined pattern.
The bone characteristics of our case are clinically and roentgenographically
typical of multiple exostosis (diaphysial aclasis)2,6,9,18,19,20. i
n this rare disease, bonethickening and deformity occur during the most active growing period. The
justaepi-physial regions of long bones, ribs, pelvis and scapulae are the most affected. Short
stature but within normal l i m i t s
1 8, bowing of the radius with ulnar wrist deviation
and humero-radial joint subluxation are characteristic and were present in the patient
here described. This disease is generally autosomal dominant but a few cases may
arise by spontaneous mutation; there are no abnormalities in karyotype or band
studies e. On the other hand, multiple exostosis cases show essentially bone impairment
alone with no skin pathology, mental deficiency or sleep-wake dysfunctions.
PSG and M S L T revealed excessive daytime sleepiness but failed tc show sleep
apnea, narcolepsy, nocturnal myoclonus or any other abnormalities. No depressive
features were noted in the PSG, as suggested in one KLS case by Reynolds et a l .
1 7in 1980. PSG recordings in KLS are few and with mixed results
8 , 1 0 , 1 2 , 1 5 , 1 7 ;some are
normal while some show characteristics of much more commom disorders like sleep
apnea or narcolepsy.
The occurence of periodic hypersomnia and mental deficiency suggest a neural
dysfunction in the sleep-wake cycle system. A congenital malformative etiology is
likely as the patient has other ectodermal dysplasias, consanguinity and no other
apparent cause for mental deficiency.
R E F E R E N C E S
1. A s s o c i a t i o n o f S l e e p D i s o r d e r s C e n t e r s — D i a g n o s t i c c l a s s i f i c a t i o n o f s l e e p a n d a r o u s a l d i s o r d e r s . S l e e p 2 : 1 , 1 9 7 9 .
2 . B r o o k s A P , W y n n e - D a v i e s R — A f a m i l y w i t h d y a p h y s e a l a n d p e r i p h e r a l d y s o s t o s i s . J M e d G e n e t 1 7 : 2 7 7 , 1 9 8 0 .
3 . C r i t c h l e y M — P e r i o d i c h y p e r s o m n i a a n d m e g a p h a g i a i n a d o l e s c e n t m a l e s . B r a i n 8 5 : 6 2 7 , 1 9 6 2 .
4 . D u f f y J B , D a v i d s o n K — A f e m a l e c a s e o f K l e i n e L e v i n s y n d r o m e . B r J P s y c h i a t 1 1 4 : 7 7 , 1 9 6 8 .
5. E a r l e B V — P e r i o d i c h y p e r s o m n i a a n d m e g a p h a g i a ( t h e K l e i n e L e v i n s y n d r o m e ) . P s y -c h i a t r Q u a r t 3 9 : 7 9 , 1 9 6 5 .
6. G a r d m e r E J , S h u p e J L , L e o n e N C , O l s o n A E — H e r e d i t a r y m u l t i p l e e x o s t o s i s : a c o m -p a r a t i v e g e n e t i c e v a l u a t i o n i n m a n a n d h o r s e s . J H e r e d 6 6 : 3 1 8 , 1 9 7 5 .
7 . G i l b e r t G J — P e r i o d i c h y p e r s o m n i a a n d b u l i m i a : t h e K l e i n e - L e v i n s y n d r o m e . N e u r o l o g y 1 4 : 8 4 4 , 1 9 6 4 .
8. G r e e n L N , C r a c c o R Q — K l e i n e - L e v i n s y n d r o m e : a c a s e w i t h E E G e v i d e n c e o f p e r i o d i c b r a i n d y s f u n c t i o n . A r c h N e u r o l 2 2 : 1 6 6 , 1 9 7 0 .
9. H o S U , L i p t o n H L — H e r e d i t a r y m u l t i p l e e x o s t o s e s w i t h m y e l o p a t h y . A r c h N e u r o l 3 6 : 7 1 4 , 1 9 7 9 .
1 0 . L a v i e P , G a d o t h N , G o r d o n C R , G o l d h a m m e r G , B e c h a r M — S l e e p p a t t e r n s i n K l e i n e -- L e v i n s y n d r o m e . E l e c t r o e n c e p h C l i n N e u r o p h y s i o l 4 7 : 3 6 9 , 1 9 7 9 .
1 2 . M e s s i m y R — H y p e r s o m n i e p é r i o d i q u e ; l e s y n d r o m e d e K l e i n e - L e v i n e t s e s p r o b l e m e s : r e v u e d e s c a s r é c e n t s . I n t J N e u r o l 1 5 : 1 1 9 , 1 9 8 1 .
1 3 . M i t l e r M — T h e M u l t i p l e S l e e p L a t e n c y t e s t a s a n e v a l u a t i o n f o r e x c e s s i v e s o m n o l e n c e . I n G u i l l e m i n a u l t C — S l e e p i n g a n d W a k i n g D i s o r d e r s : I n d i c a t i o n s a n d T e c h n i q u e s . A d d i s o n - W e s l e y P u b l , M e n l o P a r k , 1 9 8 2 , p g 1 4 5 .
1 4 . O r l o s k y M J — T h e K l e i n e - L e v i n s y n d r o m e : a r e v i e w . P s y c h o s o m a t i c s 2 3 : 6 0 9 , 1 9 8 2 . 1 5 . P l a s s e M , J o a n n a r d A , M a y n a r d R , J o u k P S , G i l l y R , B e a u d o i n g A — S y n d r o m e d e
K l e i n e - L e v i n . P e d i a t r i e 3 2 : 6 0 1 , 1 9 8 2 .
1 6 . R e c h t s c h a f f e n A , K a l e s A — A M a n u a l o f S t a n d a r d i z e d T e r m i n o l o g y . T e c h n i q u e s a n d S c o r i n g S y s t e m f o r S l e e p S t a g e s o f H u m a n S u b j e c t s . B r a i n I n f o r m a t i o n S e r v i c e / B r a i n R e s e a r c h I n s t i t u t e , U n i v e r s i t y o f C a l i f o r n i a , L o s A n g e l e s , 1 9 6 8 .
1 7 . R e y n o l d s C F , B l a c k R S , C o b l e P , H o l z e r B , K u p f e r D J — S i m i l a r i t i e s i n E E G s l e e p f i n d i n g s f o r K l e i n e - L e v i n s y n d r o m e a n d u n i p o l a r d e p r e s s i o n . A m J P s y c h i a t 1 3 7 : 1 1 6 , 1 9 8 0 .
1 8 . S h a p i r o F , S i m o n S, G l i m c h e r M J — H e r e d i t a r y m u l t i p l e e x o s t o s i s . J B o n e J o i n t S u r g 6 1 A : 8 1 5 , 1 9 7 9 .
