Adult-onset presentation of Dandy-Walker variant in siblings

ELSEVIER

Congenital Anomalies

ADULT-ONSET DANDY-WALKER

PRESENTATION OF VARIANT IN SIBLINGS

Herbert H. Engelhard, M.D., Ph.D., and Joel R. Meyer, M.D. Division of Neurosurgery, Department of Surgery (H.H.E.), and Division of Neuroradiology, Department of Radiology (J.R.M.), Northwestern University Medical School, Chicago, Illinois

Engelhard HH, Meyer JR. Adult-onset presentation of DandyWalker variant in siblings. Surg Neural 1995;44:43-47. BACKGROUND

The Dandy-Walker syndrome and Dandy-Walker variant usually present as isolated cases of hydrocephalus in pediatric patients. METHODS

AND

RESULTS

This paper consists of a case report of the adult onset of symptoms in two sisters having Dandy-Walker variant. Such an occurrence has never before been reported in the medical literature. Both patients presented with headaches and progressive neurologic deficit. On computed tomography (CT scan) of the head, both were found to have hydrocephalus, with hypoplasia of the inferior vermis. Both patients were treated successfully with ventriculoperitoneal shunting. A third sister, with a similar history, elected not to undergo CT scanning or surgical treatment.

feature being that the hypoplasia of the vermis is limited to its inferior portion [3,27]. Adult onset of symptoms in patients having the Dandy-Walker malformation or its variant is uncommon, and may occur after trauma [12,19,30]. Although the Dandy-Walker syndrome has been reported to occur in infant siblings [14,16,18,27], adult-onset symptoms from a Dandy-Walker malformation (or variant) have not, to our knowledge, been reported in siblings. The Dandy-Walker malformation has, however, been found incidentally or at autopsy [ 12,19,27]. In this paper, we describe the clinical presentation of two adult sisters with Dandy-Walker variant. Both were treated successfully with ventriculoperitoneal (VP) shunting.

CONCLUSION

Variants of the Dandy-Walker syndrome may occasionally present clinically in the adult age group. Such an occurrence in siblings is consistent with an underlying genetic etiology. KEY

WORDS

Arachnoid cephalus,

cyst, Dandy-Walker syndrome, headache, hydroposterior fossa cyst, ventriculoperitoneal shunt.

T

he Dandy-Walker syndrome usually presents with hydrocephalus early in life and is characterized radiologically by an enlarged posterior fossa and ventricular system, absent cerebellar vermis, and upward displacement of the tentorium, torcular, falx and lateral sinuses [9,10,26,29]. Other anomalies, notably involving the brain and heart, may be associated with the Dandy-Walker syndrome [8,13,14,24,28]. The Dandy-Walker variant is considered to be a less severe anomaly than the classic Dandy-Walker malformation [6,11], the key Address reprint requests to: Herbert of Neurosurgery, 233 East Erie, Suite Received August 25, 1994; accepted 0 1995 by Elsevier Science 655 Avenue of the Americas,

Inc. New

H. Engelhard, M.D., Ph.D., 500, Chicago, IL 60611. January 4, 1995.

York,

NY 10010

Division

CASEREPORTS CASE

1

A 53-year-old white woman presented with headaches and difficulty with balance while walking. The headaches occurred almost daily and would last all day. They had been increasing in intensity and frequency over a period of many years. The difficulty with balance forced her to hold onto objects while she would walk and also had been progressive over many years. The patient’s husband noted that her mental status, in terms of her ability to remember things and to perform calculations, had declined gradually over a period of many years. There was no history of trauma, even of a minor nature. The past medical history was positive for insulindependent diabetes mellitus, mild hypertension, and depression. The past surgical history was positive for tonsillectomy and eye surgery. Her medications included Lopressor, Aldactazide, Triavil, and 40 units neutral protamine Hagedorn (NPH) insulin subcutaneously per day. Neurologic examination revealed speech, com00903019/95/$9.50 SSDI 0090-3019(95)00127-P

Surg Neurol 1995;44:43-47

Engelhard and Meyer

(A-E) Representative images from the preoperative CT scan of patient 1, showing the hypoplastic inferior 0ventricular cerebellar vermis, without enlargement of the fourth ventricle or cisterna magna and mild enlargement of the system. (FJ Image from the postoperative scan showing the decrease in ventricular size after VP shunt placement.

prehension, ability to perform calculations, shortterm memory, insight, and abstract thinking to be impaired. Cranial nerve testing (including careful funduscopic exam), sensory testing, and strength were found to be normal. Cerebellar testing showed an ataxic gait and that maneuvers such as finger to finger and nose testing were performed slowly. The patient was able to walk without assistance, but only very slowly. Reflexes were 2+ and symmetric. Romberg’s sign was not present. Computerized to mography (CT) scan of the head demonstrated hydrocephalus with Dandy-Walker variant. (See Figure 1 A-E). The patient underwent a ventriculoperitoneal (VP) shunt procedure and over the next several days, her headaches and gait were noted to improve markedly. Postoperative CT scan showed satisfactory diminution of her ventricular size (Fig-

ure 1 F). Follow-up 2 years after the procedure indicated that she continued to improve with r-espect to mental status functions such as long-term memory and performance of calculations. CASE 2 The patient was the 50-year-old sister of patient 1. She had a history of several months’ duration of headaches, progressive visual loss, diplopia, and difficulty with gait. The headaches were described as intermittent and usually not severe, but the visual changes and difficulty with gait were progressively worsening. Past medical history was positive for diabetes mellitus, bilateral partial deafness, and hypertension. Her medications included hydrochlorothiazide and 10 units NPH insulin every morning and 8 units NPH insulin every night. On neurologic examination, mental status was found to

Adult Dandy-Walker Variant

Surg Neurol 1995:44:43-47

45

Representative images from the preoperative CT scan of patient 2. As with H patient 1, a hypoplastic inferior vermis and mildly increased ventricular size is demonstrated. In this patient, the fourth ventricle and cisterna magna are more prominent,

be within normal limits, although the patient was of below-average intelligence. Cranial nerve examination revealed mild bilateral third and sixth nerve palsies. No other focal motor or sensory deficits were found. The patient’s reflexes were 2+ and symmetric throughout. Cerebellar testing was accomplished slowly, but showed no significant ataxia or dysmetria. Examination of the gait showed it to be wide based: the patient had to steady herself to walk. CT scan revealed hydrocephalus with vermian hypoplasia, consistent with a Dandy-Walker variant (Figure 2). The patient was admitted to the hospital for a VP shunt procedure. This was tolerated well, and her gait was seen to improve in the immediate postoperative period. Approximately one year after the surgery, the patient was hospitalized due to liver failure, but improved with supportive care. Two years after surgery, she remained without headaches, gait difficulty, or other evidence of VP shunt malfunction.

but a large posterior fossa cyst is not present.

DISCUSSION Here we report the familial occurrence of DandyWalker variant with the adult onset of symptoms. Clinical features of the disorder, as manifested in both of the sisters, included headaches, gait difficulty, and mental status changes. The Dandy-Walker malformation may occur as a component of larger syndromes, some of which have been linked to chromosomal aberrations [8,14,15,21,22,24]. Anomalies associated with Dandy-Walker include hydrocephalus, dysgenesis of the corpus callosum, polymicrogyria, gray matter heterotopia, occipital encephalocele, polydactyly and other skeletal abnormalities, and cardiac anomalies [4,8,10,13,14,24,28]. Familial occurrence of an isolated Dandy-Walker malformation is extremely rare. Both of our patients had diabetes mellitus and one sister was hospitalized for liver disease. This raises the question as to whether or not they might have a mild form of a syndrome of familial renal-hepatic-pancreatic dys-

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Surg Neurol 1995;44:43-47

plasia and Dandy-Walker cyst, as reported by Hunter [ 15 1. Dandy-Walker malformation occurring in conjunction with severe mental retardation in infant siblings has been reported [8,16,27], and has also been related to warfarin use during pregnancy [171* Preoperatively, it is crucial to distinguish between a true Dandy-Walker malformation and an extra-axial posterior fossa arachnoid cyst [3,20]. Cystic malformations of the posterior fossa can be divided into: (1) Dandy-Walker malformation, (2) Dandy-Walker variant, and (3) mega cisterna magna [5,6].

culty walking. However, she refuses to have a CT

scan of her head.

REFERENCES

Of course, arachnoid cysts of the posterior fossa may also occur [lo]. The Dandy-Walker malformation consists of an enlarged posterior fossa with a high position of the tentorium, dysgenesis or agenesis of the vermis and cystic dilation of the fourth ventricle. Dandy-Walker variant is composed of a dysgenetic cerebellar vermis with cystic dilation of the fourth ventricle without enlargement of the posterior fossa. Mega cisterna magna includes an enlarged posterior fossa with an enlarged cisterna magna, but an intact fourth ventricle and vermis [5]. In Dandy-Walker syndrome, the cystic fourth ventricle is lined by a membrane formed by ependyma1 and pial tissue; small amounts of cerebellar tissue may also be found, particularly

Dandy-Walker malformations are believed to result from insults to the developing nervous system, which may have a genetic and/or environmental basis [5,8,18,21,24]. Symptoms are usually manifest early in life, but particularly when the variant is present, may not come to medical attention until adulthood. The cause of the disorder in our patients would seem to be genetic. They have a third sister, a nun, who suffers from headaches and diffi-

in the ventral

part of the membrane [lo]. These entities are now conceptualized as representing points along a spectrum of anomalies affecting midline brain structures, not isolated to the posterior fossa [5]. Evaluation of the supratentorial brain for associated anomalies is important, as their existence may be associated with a poorer prognosis in terms of intellectual function [5,7,13]. Current treatment of increased intracranial pressure occurring with the Dandy-Walker malformation consists of placing a VP and/or cystoperitoneal shunt. Cyst excision has also been described in the past [1,4,7,12,20,26,28]. Some controversy exists as to whether or not upward herniation after VP shunting can be a problem [12,25]. If the ventricles and “cyst” are in free communication, herniation would not be expected to occur. Herniation could occur if a VP shunt alone was placed to treat hydrocephalus caused by a noncommunicating mass lesion (e.g., cyst) of the posterior fossa. Contrast dye studies can be used to assess such communication [23]; magnetic resonance imaging (MRI) can also be very helpful in defining the anatomy [2,4,5,6,25]. Both of

the patients reported here did well with standard VP shunt procedures.

1. Almeida GM, Matushita H, Mattosinho-Franca LC, Shibata MK. Revised classification of posterior fossa cysts and cystlike malformations basedon the results of multiplanar MR imaging. AJR 1989;153:1289-300. 2. Altman NR, Naidich TP, Braffman BH. Posterior fossa malformations. AJNR 1992;13:691-724. 3. Archer CR, Darwish H, Smith K. Enlarged cisternae magnae and posterior fossa cysts simulating DandyWalker syndrome on computed tomography. Radiology 1978;127:681-6. 4. Asai A, Hoffman HJ, Hendrick EB, Humphreys RP. Dandy-Walker syndrome experience at the Hospital for Sick Children Toronto. Pediatr Neurosci 1989;15: 66-73. 5. Barkovich AJ. Pediatric Neuroimaging. New York:

Raven Press, 1990:115-21. 6. Barkovich AJ, Kjos BO, Norman D, Edwards MS.

Dandy-Walker syndrome: management of DandyWalker syndrome. Childs Nerv Syst 1990;6:335-7. 7. Bindal AK, Storrs BB, McLone DG. Management of the Dandy-Walker syndrome. Pediatr Neurosurg 1990-l; 16:163-g. 8. Buttiens M, Fryns JP, Van den Berghe H. An apparently new autosomal recessive syndrome with facial dysmorphism, macrocephaly, myopia and DandyWalker malformation. Clin Genet 1989;36:451-5. 9. Dandy WE. The diagnosis and treatment of hydrocephalus due to occlusions of the foramina of Magendie and Luschka. Surg Gynecol Obstet 1921;32: 112-24. 10. Diebler C, Olivier D. Dandy-Walker syndrome. Pediatric neurology and neuroradiology. Berlin: SpringerVerlag, 1987:41-51. 11. Estroff JA, Scott MR, Benacerraf BR. Dandy-Walker variant: prenatal sonographic features and clinical outcome. Radiology 1992;185:755-8. 12. Fischer EG.Dandy-Walker syndrome: an evaluation of surgical treatment. J Neurosurg 1973;39:615-21. 13. Golden JA, Rorke LB, Bruce DA. Dandy-Walker syndrome and associated anomalies. Pediatr Neurosci 1987;13:38-44. 14. Herriot R, Hallam LA, Grey ES.Dandy-Walker malformation in the Meckel syndrome. Am J Med Genet 1991;39:207-10. 15. Hunter AG, Jimenez C, Tawagi FG. Familial renalhepatic-pancreatic dysplasia and Dandy-Walker cyst: a distinct syndrome? Am J Med Genet 1991;41:201-7. 16. Jenkyn LR, Roberts DW, Merlis AL, Rozycki AA, Nor-

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dgren RE. Dandy-Walker malformation in identical twins. Neurology 1981;31:337-41. Kaplan LC, Anderson CG, Ring BA. Congenital hydrocephalus and Dandy-Walker malformations associated with warfarin use during pregnancy. Birth Defects: Original Article Series 1982;18:79-83. Lehman RM. Dandy-Walker syndrome in consecutive siblings: familial hindbrain malformation. Neurosurgery 1981;8:717-9. Lipton HL, Preziosi TJ, Moses H. Adult onset of the Dandy-Walker syndrome. Arch Neurol 1978;35:672-4. Marinov M, Gabrovsky S, Undjian S. The DandyWalker syndrome: diagnostic and surgical considerations. Br J Neurosurg 1991;5:475-83. Melaragno MI, Brunoni D, Patricia FR, Corbani M, Mustacchi Z, Santos RDCSD,Lederman HM. A patient with tetrasomy 9p, Dandy-Walker cyst and Hirschsprung disease.Ann G&net 1992;35:79-84. Nyberg DA, Mahony BS, Hegge FN, Hickok D, Luthy DA, Kapur R. Enlarged cisterna magnaand the DandyWalker malformations: factors associated with chromosome abnormalities. Obstet Gynecol 1991;77:436-

42. 23. Ozgen T, Acikgoz B. CSFDynamics in Dandy-Walker

syndrome. Acta Neurochir (Wien) 1990;104:54-8. 24. Pettigrew AL, JacksonLG, Ledbetter DH. New X-linked

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mental retardation disorder with Dandy-Walker malformation, basal ganglia disease,and seizures. Am J Med Genet 1991;38:200-7. Pillay P, Barnett GH, Lanzeiri C, Cruse R. DandyWalker cyst upward herniation: the role of magnetic resonance imaging and double shunts. Pediatr Neurosci 1989;15:74-9. Sawaya R, McLaurin RL. Dandy-Walker syndrome. J Neurosurg 1981;55:89-98. Stall C, Huber C, Alembik Y, Terrade E, Maitrot D. Dandy-Walker variant malformation, spastic paraplegia, and mental retardation in siblings. Am J Med Genet 1990;37:124-7. Unsgaard G, Sand T, Stovring J, Ringkjob R. Adult manifestation of the Dandy-Walker syndrome. Neurochirurgia (Stuttg) 1987;30:21-3. Walker AE. A case of congenital atresia of the foramina of Magendie and Luschka. J Neuropathol Exp Neurol 1944;3:368-73. Yamamoto Y, Waga S. Asymptomatic Dandy-Walker variant in an adult. Surg Neurol 1984;22:241-2.

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COMMENTARY

The paper by Engelhard

and Meyer is interesting, because it is the first description of a symptomatic Dandy-Walker variant in two adult siblings, with another sister suspected to have the same malformation. Since the introduction of CT and MN to the diagnostic armamentarium, more and more cases of previously described diseases or syndromes have been reported. Among the 37 references in this paper, six [11,19,20,27,31, and 371 deal with the description of new syndromes associated with Dandy-Walker malformations, all except one of them published in the 1990s. Although the Dandy-Walker is almost a pediatric anomaly, more reports of adult patients have appeared in the literature during recent years [25,38,39]. I did an extensive review of the Spanish, French, and German literature of the past 5 years, and found no report of adult siblings with symptomatic Dandy-Walker variant. So, as the authors point out, their report is the first one, and goes along with the underlying genetic etiology of this pathology. Fernando

Some classifications

Rueda-France, M.D. Mexico City, Mexico

of congenital

anomalies,

nota-

bly the one from the March of Dimes, call the Dandy-

Walker variant a congenital abnormality of genetic origin, and state that there is a possibility of several siblings having the same disorder. The adult presentation of the symptoms is not unusual. I have had several patients myself, but I may say that I have never seen this condition in two siblings. Philadelphia,

Luis Schut, M.D. Pennsylvania