(no)extreme variant of septo-optic dysplasia

8/2/2019 (NO)Extreme Variant of Septo-optic Dysplasia

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Extreme variant of septo-optic dysplasia*K . S T E H R I , 1J. M A Y E R ' . R . A. P F E l F F E R j a n d R . R E I F '

AHSTKACI-. A n c w b o r n l ~ m a l e i s d c m o n s t r a t e d , t h e f i r s t c h i l d o f h c a l t h y u n r e l a t e dparentswho wah born after an uneventful pregnancy. Coniputerixd tomography of the brainrevealed gross m alforma tions of the parietal and occipital lobes. of the cerebellum a nd ofmidline structures . T h e pictures are reminiscent of hydranencephaly. The association withbilateral colobom a of th e papilla and dia betes insipidus is considered i t n extreme variant ofsepto-o pt ico dysplas in.Ke.1.~ ~ ) r ( l . s :ptic nerve ; septo-optico dysplasia; coloboma of choroid

V a r io u s a s s o c i a t i o n s of m o r p h o l o g i c a l a b -no rmal i t ies of t h e e y e s a n d m id - li n e s t r u c tu r e so f the b ra in a n d f ac ia l c le ft s ( 'mid l ine fu s iondefects ') have bee n heur is t ically c lass ified i n t oc l inica l en t i t i es , the cau ses of w h i c h a r e h e t e r -o g e n e o u s, m o st l y u n k n o w n t h o u g h p r o b a b l yn o t g e n e ti c ( T a b l e I ) . T h e a s s oc i at i on of hy-p o p la s ia o f t h e o p t i c n e rv e a n d a g e n e s i s of th es e p tu m p e l lu c id un i w a s f ir st d e li n e a t e d b y D eM ors ier in 1957. Be c a u s e o f f r e q u e n t d i s o r d e r so f t h e p i t u i t a r y f u n c t i o n s i t was r ecen t lyt e r m e d S e p to - O p t i c o -p i t u i ta r y D y s p l a s i as v n d r o m e ( A c er s, I98 I ), b u t i t poss ib ly r ep -r c s e n ts a m a l f o r m a t iv e c o n i p le x a n d i s d u e t o as c q u e n c e o f ( s e c o n d a r y )d i s o r d e r s in m o r p h o -g e ne s is . S e v e r a l p u b l i s h e d c a s e s a n d t h e o b -sc rva t ion r ep o r ted here, p rov is iona l ly hea dedSOD, s h a r e m a l f o r m a t i o n s w i t h d if fe r e nt e n -t i t i e s , p a r t i c u l a r ly h o lo p r o s e n c e p h a ly a n dr a is e d i a g n o s t i c a n d n o s o lo gi c a l p r o b l e m s .* -Iclth.c,s.\ ,/iu . o i . r . c , . \ l ) o t i ( l c ~ t i i ~ i , :Prof. l l r . I < . A .1'1 eil'fer, Inst t i t fiir H u niii ngcnet ik. Schwa ba cha 11nge10. 11-8520 Erlangen. HKI)~.

C A S E R E P O R TS t W 830926 is the only child of healthy unre-lated parents. At her birth the father was 37years and the mother was 33 years of age.During the third month of pregnancy she suf-fered from fever but did not take any medica-ments. Post-term delivery was uneventful. T heplacenta was small an d the umbilical c ord ap -peared th in . Apgar notes were 7-9-10. Weightwas 2800 g, length w as 5 cm, head circumfer-encewas32 cm . She wasadmit ted to a pediatr ichospital because of shrill crying and unusualcraniofacies with sloping forehead and hypo-telorism. The anterior fontanelle had a size ofI cm?. Except for short little fingers and pesadductus no dysmorphic features were noti-ced . The sun set t ing phenomenon was notobserved. There was general muscular hypoto-nia. Malformations of the heart and kidneyswere not revealed an d metab olicdisorde rs wereruled out as were prenatal infections.The EEGshow ed reducedampli tudeover theentire vertex without evidence of focal abnor-malities. Sonographicexa mination of the brainsuggested hydranen cepha ly with absence of theseptum pellucidum and fusion of the lateral-

Oplitlialtnic Puediarrii~s tid GenericsP r ~ ( ~ w ( l i n g . ~lnt l Joinr Mwting of thc Ititernarionul Soc iet,l.jior Genetic Ey e Diseaseund the International Soc,ieri',forPaetliatrii, 0 phrh alniolog.r.[iliivii, Belgiirm. 11-11 Mu!, 1984. p p . 187-1920 . I r o l i r s Press Anistertlani 1985

198s. V o l .S v N o . 3 , pi>. SY-164 159 (187)

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ventricles. enlargement of the third vcntriclcand hypoplasia of the cercbellurn.A CA T scan of the brain did not visualizemidline structu res, only o ne large ventricle he-ing present. Partial aplasia o ft he I ' rontal parie-tal temporal and occipital lobes w as suggestcd(Fig . I ).0p h hit mologica I find irigs : t he pa pe bra 1fissures were u psla n t i ng. M o I i t y ii nd p u pi I lii ryreactions were norm al. The right opticdisk wiisnormally colored. There was a bridged colobo-ma of the retina and chor oid (I-ig. 2 ) . Hie lett

papilla appeared morning glory l ike (Hand-mann 's anomaly) and a t rophic . surrounded byla rgechoroid and rc t ina la t rophies( Fig . 3) .T hemacula, retinal vessels and the peripheralregions of the fundus appeared normal.Pitressin sensitive diabetes insipidus w as no -ticed at the age of two months and has beensuccessfully treated. There w a s neither pro-longed neonatal jaund ice n or evidence o f hypo-glycemic crises.A pericentric inversion oft he hcterochrom at-ic part of a chromosome 9 was noted i n th epatient and in his mother.A t the age of eight months the patient diedsuddenly and unexpected. Macroscopicii l ex-aminat ion of the brain showed aplasia of theparietal temporal and occipital lobes whichwere replaced by a large cyst, absence of thcseptum pellucidum a nd a s ingle frontal ventri-cle, hypoplasia of the corp us callosum. absenceof the olfactory tracts. Microscopical studiesare still lacking (Fig . 4).Right arched aorta and hypoplastic kidney\were noted./ig. . Cornpi i ter ixd tomography of the brain a t theape or 14 davs. - -~ _ _ _

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/../,y. 2. F u n d u s o f th e right ey e b i t h bridged c o l o h o m a of the choro id .

/ 1 , ~ . . F u n d u s of t h e l e l t cye wi th large per ipnpi l laryH t cophy . I .7 .y .1. Brain occipitallp displaced i t , . s i / i / .. -

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C O M M E N T

rhe pat ient exhibits importa n t m a fo ma-tions of the brain tentatively classified ashydranencephaly, agenesis of the septumpellucidum, absence of the olfactory tractsassoc ia ted wi th choroida l colobomata .Neurohormonal diabe tes ins ipidus wi thoutevidence of adenohypophyseal def iciencysuggests dysplasia of the pos te r ior lobe only.

The significance of the abno rma lities of th egreat vessels an d kidneys is un kn ow n and willnot be discussed further.Hydranencephaly and hypoplas ia of theop tic nerve was note d by Mosiercvul. (1978 )ina nine-month-old child. Autopsy revealedlarge bilateral lluid filled cysts with trans pa r-ent membranes which replaced the f rontalpar ietal arid super ior aspect o f tem por al lobes,the fornixand thecorpus ca l losum be ing pres-ent . Th e cerebe llum and the bra in s tem ap-peared normal.

1 he th i rdcaseofPa te l c tu l . ( 1975) i squo tedbecause in the t hree-month-old child hypopla-sia of the optic nerve which con tained only afew myelinated fibers was associated withmicrencephaly and absence of the olfactorybulbs . The anter ior por t ion of t he corpuscallosum w asdeficient but the septu m pelluci-durn was present . The anter ior lobe of thepitui tary gland w as considered n orm al where-as the p osterior lobe was not identified. V ari-ab ledegreeso f fus ionof the f ron ta l horns w ithdilata tion of the lateral ventricles may be ob-served. The case of Ellenberger & R u n y a n(1970)could serve asan exa mp le because PEGshowed enlargement of the anter io r par t of th elateral ventricles which were partially fused.

T h e patie nt was a 23-year-old female withaverage intel ligence, short s tatu re and hypo-thyroidism wh o suffered from bilateral hemi-anops ia . The r ight opt ic disk on ly appeared

pale and slightly tilted.Colobom atous anom a l i e s of the fundus

were no ted in only few patients in w ho m ab -sence of the septum pellucidum had beenshow n. A cers( 198I ) ists threecases inasc r iesof 45 but nei ther Edwards & l . aydcn (1 9 7 0 )nor Wal ton & R o b b ( 1 9 7 0) i n a total of 45cases mentioned any retinal abnormality.Ha r r i s& Ha as( 1972) noted a s rna l lcolobom ao f t h e left eye. Ab sence of th e septum pe lluc i-durn a n d a single midline ventricle was visual-ized. Growth hormone def iciency was con-firmed after hypoglycemic stimulation. I n ;I12-year-old girl(Stewart r v u / . - 19x3) howeverthe septum pellucidurn appeared intact . Acoloboma of the left optic nerve was noted.The re was m icrophth almos of the r ight side.CA I - scan showed absence of t he corpu s ca llo-sum. S h e presented fea tures o f midline cleftsyn drom e and suffered fro m isolated g rowthhor mone d e c e ncy a n d hyperp ro I ct ne n ia ,H ypertelor ism. comp lete bi lateral co lob om a-taan d b ifid uvu la in a m a lew i thabsenceo f thecorp us cal losum , di latat ion o f t he ventr icularsystem an d hy pop lasia of the vermis cerebelliwere the m ain ano ma lies studied by FranCoisel a/. (1973). Hypothalamic deficiency waslikely because of hypogenitalism and hypo-plasia of the thyroidgland de tec teda tauto psy.

The frequency of pi tui tary disorders isnotew orthy. First emphasized by H oyt ct a/.(1970) and Kaplan 61 a/. 1970 ) . Acers (19 81)found s ix pa t ients out o f4 5 who had c l in icaleviden ce of hypo fun ction . In all of them par-t ia l or tota l absence of the septum pellucidumcould be shown. Th e f requency is likely to bchigher , perhaps even in half of all cases.H u s e m a n e / ul . ( 1978) collected 18 cases withhypopitui tar ism from the l i terature, s ix ofwhom had adiuret ic hormone del iciency.Since in five patients examined by Krause-Rrucker & G a r d n e r ( 1980) grow th horm one

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deficiency was consistently found but adiu ret-in insufficiency i n only three of them, onecould conclude(Stewartet al . , 1983) that dia-betes insipidus tends to occur in those patientswith multiple troph ic horm onedeficienc ies. I fthis holds true anterio r h ypothalam ic lesionsrnay be suspected. The endocrinological s tu -dies of Huseman et d. 1978) could supportthis hypothe sis. I t is however noteworthy thati n the case of Patel et ul. (1975) mentionedabove the anterior lobe was normal but theposterior lobe was absent. Since both lobeshave different origins one would expect defi-ciencies of the aden ohy pop hys is in cleft facialand median syndromes and possibly in holo-prosencephaly. The literature provides littleinformation and the finding of growth hor-mone deficiency in cleft lip an d p alate (L aro net al., 1969) seems to be rather infrequent. asthe neurohy pophy sis develops from an invagi-nation of the diencephalic floor dysplasia an ddys func tion is expected in septo-optic dyspla-sia. T o Bruyn, in 1977, the intriguing clinicalentity of S O D the cause of which is unkn ow n,has no unifying pathogeneticconce pt. Indeed,the asynchrony of the differentiation of theoptic nerve (six to seven weeks of gestation)and of theformat ionof theseptumpel lucidum( 15-2 weeks) is difficult to co m pre he nd .However, i f one considers the ana tom ic sub-

strate of the septum pellucidum, the chiasmaand o fthe posterior lo be ofth e pi tui taryglandas well. the close topic an d tem pora l relation-ship makes an a bno rma l m orphogenesis l ike-ly. The rostra1 wall of the prosencephalonconstitutes the commissural plate and is con-tinued by the diencephalic lamina terminalis.When the cerebral hem isphereseva ginateandentail the eno rm ou s growth of the corpuscallosum the commissural plate which con-nects the fornix hippocampi with the corpuscallosum is stretched. Th is is the septu m pel-lucidum which sepa rates the lateral ventricles.I t would be absent whenever the lamina ter-minalis is deficient. One would also expectab no rm al invagination of th e floor of the thirdventricle giving rise to the neurohypophysisbut a disturbance of the optic chiasma, too.The fibers of the ganglionic cells reach thechiasm a by the2 2 mm stage, the infundibulumis formed at the sam e time. I f only a par t of thef ibersareal lowed tocross , theo pt icne rvea nddisk would be hypoplastic. Th e choroidal col-ob om a inthis patient is du eto proximal failureof the optic fissure which closes during theseventh week of gestation ( I5 mm ). Any tera-togenic action would have operated earlierand therefore more severe consequencesshould be expected than i n S O D .

K E F E R E N C E SAC ER S, T h. E.: Optic nerve hypoplasia: septo-optico-pituitary dysplasia syndrome. Trat1.v.AMY ophrhol. Sot,.

7 9 :425-457. 1981HR L I Y N , C . W . : Agenesis of septi pellucidi. cavu m septi pellucidi. cavum v ergae. and cavu m veli interpositi. In:Handbook ofC/itiicd Nruro /og . i , ( . J . Vinken and G . W . Bruyn. eds.), Vol. 30, p p . 209-336. North-Holland,Amsterdam 1977I ) E M O R S I E R , G . : Etudes sur les dysraphies cranio-encephaliques. 3. Agenesie d u septum lucidum avecmalforma tion du tractus optiqu e. Ladysplas iesepto-opt ique.S c / i ~ ~ i ; .r ch . N m r o l . P.v,i,c,/iia/.7: 267-202, 1956F DW A R D S , W . C. & L A Y D E N . W . E . : Optic nerve hypoplasia. Airier. J . Oph/liul.70: 950-959. 1970F L L E N B E R G E R ,C.& R U N Y A N , T h . E. :Holoprosencepha ly with hypoplasiaoftheopticnerves,dwarfism,andagenesis of the septum pellucidum. A m ~ r .I . Op/ i /hu l . 70: 960-967. 1970

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I- K A N CO S. I ,.ECi

(no)extreme variant of septo-optic dysplasia

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