Introduction

The term ‘cerebellar hypoplasia’ describes a heteroge-neous group of conditions that may be acquired sec-ondary to prenatal infection or exposure to teratogens.Genetic causes include single gene disorders, chromo-some abnormalities, malformations, metabolic disease,and the pontocerebellar hypoplasias. The LondonNeurogenetics Database [1] lists 311 genetic causes ofcerebellar hemisphere and/or vermis hypoplasia/aplasia,all with varying degrees of disability and differingprognoses, making counselling of these families difficult.

The abnormalities are usually classified radiologically[2], but this type of classification is limited because itdoes not take account of intrafamilial phenotypic vari-ability seen in single gene or metabolic disorders, or theembryological origin.

Progress with neuroimaging has allowed more de-tailed examination of the developing fetal brain and mayprovide further information [3]. This report describes acase in which cerebellar hypoplasia was detected at20 weeks’ gestation. Both fetal and neonatal MRI scanswere undertaken and provided further informationallowing for accurate counselling of the family. This case

Emma McCann

David Pilling

Markus Hesseling

Devender Roberts

Nim Subhedar

Elizabeth Sweeney

Pontomedullary disconnection: fetaland neonatal considerations

Received: 7 January 2005Accepted: 14 February 2005Published online: 6 April 2005� Springer-Verlag 2005

Abstract The cerebellar and ponto-cerebellar hypoplasias present a un-ique challenge when detected in thedeveloping fetus. A diverse aetiologyand prognosis make counselling ofthese families difficult. Advances infetal imaging allow for more accu-rate diagnosis and counselling, butpostnatal MRI is still required. Acase is presented in which cerebellarhypoplasia was detected at 20 weeksgestation. Later fetal imaging pro-vided further information, but adiagnosis of pontomedullary dis-connection was not made until thepostnatal MRI scan. The clinicalfindings and possible causes of suchpontocerebellar abnormalities arediscussed.

Keywords Cerebellum ÆHypoplasia Æ Pontocerebellarhypoplasia Æ Fetus Æ MRI

Pediatr Radiol (2005) 35: 812–814DOI 10.1007/s00247-005-1455-1 CASE REPORT

E. McCann (&) Æ E. SweeneyDepartment of Clinical Genetics,Royal Liverpool Children’s Hospital,Eaton Road, Liverpool L12 2AP, UKE-mail: emma.mccann@rlc.nhs.ukTel.: +44-151-2525238Fax: +44-151-2525951

D. PillingDepartment of Paediatric Radiology,Royal Liverpool Children’s Hospital,Eaton Road, Liverpool L12 2AP, UK

M. Hesseling Æ N. SubhedarDepartment of Neonatology,Liverpool Women’s Hospital,Crown St., Liverpool L8 7SS, UK

D. RobertsDepartment of Fetal Medicine,Liverpool Women’s Hospital, Crown St.,Liverpool L8 7SS, UK

demonstrates the difficulty in investigating and manag-ing fetal cerebellar hypoplasia.

Case report

A 23-year-old woman, gravida 2 para 1, presented at20 weeks’ gestation following a pregnancy that had beenuneventful up to this point. A routine fetal anomaly USscan revealed a hypoplastic cerebellum (15 mm; normalmeasurement 20 mm) along with a dilated cisternamagna (11.1 mm; normal <10 mm), but no other brainabnormalities. Bilateral talipes was also detected, butthere were no structural abnormalities. Karyotype andcongenital infection screen, including cytomegalovirus(CMV), was normal. Further US scanning at 25 weeks’gestation showed two very hypoplastic cerebellar hemi-spheres but no Dandy-Walker cyst. Fetal MRI at thisstage confirmed the presence of severe cerebellar hypo-plasia and revealed pontine hypoplasia. The family wascounselled regarding a possible diagnosis of pontocere-bellar hypoplasia (PCH) and offered a guarded prog-nosis. The couple elected to continue with thepregnancy.

A male was born at 38 weeks’ gestation followingspontaneous onset of labour. Seizures were evident at

delivery and jaw spasm prevented intubation until18 min of age. Apgar scores were 6 at 1 min, 7 at 5 minand 10 min. Birth weight was 3.14 kg (50th centile) andoccipitofrontal circumference was 34.5 cm (50th centile).He was noted to be hypertonic with abnormal posturing.There were no dysmorphic, ophthalmological or neu-rocutaneous features. Neonatal MRI confirmed cere-bellar and vermian hypoplasia (Fig. 1). It also revealeddiscontinuity between the medulla and pons, which wereconnected by a strand of tissue thought possibly to be ablood vessel. The optic nerves were relatively hypo-plastic (Fig. 2). No other brain abnormality was present.The family elected to withdraw supportive care and thebaby died shortly afterward. Limited autopsy confirmedthe intracranial abnormalities; skeletal survey and bodyMRI were normal.

Discussion

Cerebellar hypoplasia and brainstem atrophy/hypopla-sia are known associations. Fetal onset of PCH raisesthe possibility of several diagnoses, including PCH types1 and 2 [Mendelian Inheritance in Man (MIM) 607596

Fig. 1 Sagittal MRI demonstrates virtual discontinuity betweenthe medulla and pons, the only connection being a thin strand oftissue

Fig. 2 Axial MRI shows optic nerve hypoplasia. Note also thehypoplastic cerebellar hemispheres and vermis

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and MIM 277470, respectively http://www.ncbi.nlm.-nih.gov/omim], Walker–Warburg syndrome (MIM236670), muscle-eye-brain disease (MIM 253280), andmembers of the group of carbohydrate deficiency gly-coprotein disorders (CDGP) (now known as congenitaldefects of glycosylation).

The PCH 1 and 2 are autosomal recessive neurode-generative disorders characterized by their clinical andMRI findings [4]. The PCH 1 is characterized by centraland peripheral motor dysfunction. It presents frequentlywith congenital contractures and respiratory insuffi-ciency. Death usually occurs within the first year of life.The hallmark of type 2 is severe chorea. Other featuresinclude progressive microcephaly and severe impairmentof mental and motor development. Death frequentlyoccurs in childhood. Although these conditions wereinitially considered in our patient, the clinical and MRIfindings made these diagnoses very unlikely. The PCHwas thought unlikely because of the discontinuity be-tween medulla and pons.

Walker-Warburg syndrome is characterized byhydrocephalus, agyria, retinal dysplasia and ocularanterior chamber abnormalities, which were not presentin our patient. Muscle-eye-brain disease is thoughtsimilar to Walker-Warburg syndrome and is character-ized by muscular dystrophy with high serum creatinekinase, a neuronal migration problem, and eyeinvolvement. The CDGP disorders are an importantgroup of conditions to exclude, as they may have cere-bellar hypoplasia as a feature; PCH is more unusual, buthas been reported [5]. Serum transferrin isoelectricfocusing is currently the method of choice for diagnosingCDGP [6]. This is an important diagnosis when coun-selling parents in regard to recurrence risk.

A previous case report describes a child with similarMRI findings to our case, but with no flow void in theexpected region of the basilar or distal vertebral arteries

[7]. A vascular insult was suspected to be the most likelycause. Although it is possible that our case also suffereda vascular incident in early fetal life, the presence ofoptic nerve hypoplasia casts some doubt on thisdiagnosis.

The cerebellum is one of the first parts of the brain todifferentiate, at around 34–42 days’ gestation. It doesnot complete growth until the end of the first postnatalyear, and thus it is susceptible to developmental or cel-lular disruptions that can manifest as structural defectsor neoplastic problems, respectively. The cerebellum andpons arise from the rhombencephalon, the most caudalpart of the primary vesicle. The rhombencephalon givesrise to two vesicles—the metencephalon (precursor ofthe cerebellum and pons) and the myelencephalon(precursor of the medulla oblongata). Differentiationinto the various components is under tight genetic con-trol and involves a number of developmental genes [8]and patterning organizers [9]. It is possible that an earlyinsult, vascular, genetic or teratogenic interfered withthe timing of development of the pons and medullaoblongata and thus disrupted normal growth leading tothe disconnection.

The various aetiological factors contributing tocerebellar hypoplasia make counselling of couples withan antenatal diagnosis difficult. Counselling relies onantenatal imaging, which can be limited despite use ofdifferent modalities. The underlying diagnosis istherefore often unknown with the result that theprognosis varies widely. Cerebellar hypoplasia/PCHsyndromes may be lethal in late fetal or early neonatallife; alternatively some have relatively mild pheno-types. A multidisciplinary team approach is neededinvolving obstetrician, paediatric radiologist, paediatricneurologist, neonatologist and geneticist in order toprovide the family with the most accurate informationpossible.

References

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2. Patel S, Barkovich AJ (2002) Analysisand classification of cerebellar malfor-mations. AJNR 23:1074–1087

3. Whitby EH, Paley MN, Sprigg A, et al(2004) Comparison of ultrasound andmagnetic resonance imaging in 100 sin-gleton pregnancies with suspected brainabnormalities. Br J Obstet Gynecol111:784–792

4. Barth P (2000) Pontocerebellar hypopla-sia—how many types? Eur J PaediatrNeurol 4:161–162

5. Barth P (1993) Pontocerebellar hypopla-sias. An overview of a group of inheritedneurodegenerative disorders with fetalonset. Brain Dev 15:411–422

6. Jaeken J (2004) Congenital disorders ofglycosylation (CDG): update and newdevelopments. J Inherit Metab Dis27:423–426

7. Mamourian AC, Miller G (1994) Neo-natal pontomedullary disconnection withaplasia or destruction of the lower brainstem: a case of pontoneocerebellarhypoplasia? AJNR 15:1483–1485

8. Wang VY, Zoghbi HY (2001) Geneticregulation of cerebellar development.Nat Rev Neurosci 2:484–491

9. Wurst W, Bally-Cuif L (1999) Neuralplate patterning: upstream and down-stream of the isthmic organizer. Nat RevNeurosci 2:99–108

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