Isolated Rhombencephalosynapsis: a Rare Disease

Archive of Medical Investigations / 2016; 1 (1): 18-20 Tıp Araştırmaları Arşivi doi: 10.5799/ahinjs.03.2016.01.0004 CASE REPORT / OLGU SUNUMU

Isolated Rhombencephalosynapsis: A rare disease

Fesih Aktar1, Kamuran Karaman2, Serap Karaman2, Gökmen Taşkın2, Hüseyin Çaksen2

ABSTRACT Rhombencephalosynapsis is a rare congenital malformation of the cerebellum characterized by hypogenesis or agenesis of the vermis and fusion of the cerebellar hemispheres with or without fusion of the dentate nuclei and superior cerebellar peduncles. Clinical presentation and prognosis are variable and are primarily determined by the presence and extent of concomitant supratentorial anomalies. Survival time of cases are generally short and they can rarely survive into early adulthood. A four year-old girl patient presented with incapability to work. Her height, weight and head circumference were <3 percentile. She had psychomotor retardation, microcephaly, broad forehead, and superior lip shift down, dysplastic ear, strabismus, bilateral pes equinovarus and hammer toe in both feet. The deep tendon reflexes were increased and there was spasticity in lower extremities. In brain magnetic resonance imaging; the cerebellar hemisphere was fused on middle line. Cerebellar vermis, septum pellisidium and corpus callosum were not observed. The posterior horns of the lateral ventricle are separated. This case was presented with clinical features because of it is a rarely reported disease in literature. Arch Med Invest 2016; 1 (1): 18-20 Key words: Rhombencephalosynapsis, congenital malformation, cerebellum, child

İzole Rombensefalosinapsis: Nadir bir hastalık

ÖZET Rombensefalosinapsis, vermis agenezisi veya hipogenezisi ve serebellar hemisferlerin dentat nükleus ve superior serebellar pedinküller ile birlikte olan veya olmayan füzyonu ile karakterize, nadir görülen serebellumun konjenital bir mal- formasyonudur. Klinik bulgular ve prognoz primer olarak eşlik eden supratentoriyal anomalilere bağlı olarak değişmek- tedir. Olguların yaşam süresi çoğunlukla kısadır ve nadiren erken erişkin döneme kadar yaşarlar. Dört yaşında kız hasta yürüyememe şikâyeti ile getirildi. Boy, vücut ağırlığı ve baş çevresi 3 persentilin altında idi. Hastada psikomotor gerilik, mikrosefali, alın genişliği, üst dudağın aşağı doğru dönük olması, displastik kulak, strabismus, bilateral pes ekinovarus ve her iki ayak başparmaklarında çekiç parmağı vardı. Derin tendon refleksleri artmıştı ve alt extremitelerde spastisitesi mevcuttu. Beyin manyetik rezonans görüntülemede, serebellar hemisfer orta hatta füzyone ve serebellar vermis, septum pellisidium ve corpus callosum izlenmedi. Lateral ventrikülün posterior hornları birbirinden ayrık idi. Literatürde nadir olarak bildirilen bu vakanın klinik özellikleri ile birlikte sunulması amaçlandı. Anahtar kelimeler: Rhombencephalosynapsis, konjenital malformasyon, serebellum, çocuk

INTRODUCTION Rhombencephalosynapsis (RES) is a rare congenital case has been presented because of it is a rarely re- malformation of the cerebellum characterized by hy- ported disease in literature. pogenesis or agenesis of the vermis and fusion of the cerebellar hemispheres with or without fusion of the CASE REPORT dentate nuclei and superior cerebellar peduncles [1,2]. Since then, fewer than 100 cases have been reported. A four year-old girl patient applied for incapacity to Clinical presentation and prognosis are variable and walk. Her medical history revealed that she started to are primarily determined by the presence and extent of talk at age of two, to sit without support at age of three concomitant supratentorial abnormalities [1,2]. This and she still cannot walk. According to her anamnesis, she was born at home by normal spontaneous vaginal

1 Dicle University Faculty of Medicine, Department of Pediatric, Diyarbakir, Turkey 2 Yüzüncü Yıl University Faculty of Medicine, Department of Pediatric, Van, Turkey Correspondence: Fesih Aktar; Dicle University Medical Faculty, Department of Pediatric, Diyarbakır, Turkey Email: [email protected] Received: 03.05.2016, Accepted: 14.05.2016 Copyright © Archive of Medical Investigations / Tıp Araştırmaları Arşivi 2016, All rights reserved Aktar F, et al. Isolated Rhombencephalosynapsis 19 way on time, she cried immediately after the birth and she did not go through jaundice or cyanosis. There was no particularity in her family history. In physical ex- amination, her height was 75 cm (<3 percentile), her body weight was 8300 gram (<3 percentile), and her head circumference was 48 cm (<3 percentile). She had psychomotor retardation. The patient presented microcephaly, broad forehead, and superior lip shift down, dysplastic ear, strabismus in right eye, bilateral pes equinovarus, and hammer toe in both feet. The deep tendon reflexes were increased and there was spasticity in lower extremities (Figure 1, 2). Hemo- gram, biochemical and urinary analyses, coagulation tests and thyroid hormone, vitamin B12, folate and ferritin levels were normal in laboratory analyses. In Figure 2. Bilateral pes equinovarus, hammer toe in both brain magnetic resonance imaging, for posterior fossa feet and spasticity series evaluation; the cerebellar hemisphere was fused on middle line and the cerebellar vermis was not observed (Figure 3). In the evaluation of supratentorial sections; the septum pellisidium was not observed. The corpus callosum, the corpus posterior and the splenium were not observed (dysgenesis of the corpus callosum). The third and lateral ventricles are dilated. The posterior horns of the lateral ventricle are separated (secondary to dysgenesis of the corpus callosum) (Figure 4). Diagnosis of rhombencephalosynapsis has been established according to the radiological findings. The electroencephalogram, visually evoked potential analysis, brainstem auditory evoked potential, echocardiography, abdomen and urinary system ultra- sonography and skeletal survey analyses performed systematically to determine the association to defects Figure 3. Absence of the cerebellar vermis in T2 weighted of this syndrome, were normal. cross-section

Figure 1. Microcephaly, broad forehead, superior lip shift Figure 4. Absence of the septum pellisidium in T1 weighted down, dysplastic ear, strabismus cross-section, the third and lateral ventricles are dilated secondary to dysgenesis of the corpus callosum and the posterior horns of the lateral ventricle are separated Arch Med Invest www.armedin.org Vol 1, No 1, June 2016 20 Aktar F, et al. Isolated Rhombencephalosynapsis

DISCUSSION MRI include; deficiency or absence of the septum pellucidum, dysgenesis of the corpus callosum and Common clinical presentations of disease include the anterior commisure, fused fornices and thalami developmental delay, mild truncal ataxia, epilepsy, [5]. Superior and middle cerebellar peduncles, along spasticity, hypotonicity, strabismus, involuntary head with dentate nuclei and inferior colluculi, are gener- movements, severe motor and cerebellar dysfunction ally fused, giving rise to the typical diamond-shaped and a few reports of psychiatric disturbances and self- fourth ventricle on axial scans. Aqueductal stenosis is mutilating behaviors [2-4]. Our case presented devel- commonly associated, and it represents as congenital opmental retard, psychomotor retard, spasticity and hydrocephalus [7]. In our case, the cerebellar hemi- strabismus. Multiple authors have reported instances sphere was fused on middle line and the cerebellar of craniofacial dysmorphism, including hypertelorism, vermis, septum pellisidium and corpus posterior and low-set ears, and high arched palate in patients with splenium of the corpus callosum were not observed in RES [1,2]. brain magnetic resonance imaging. Rhombencephalo- The most commonly reported systemic malfor- synapsis diagnosis has been established according to mations involved the musculoskeletal system, but the radiological findings of our patient who presented abnormalities in the cardiovascular, urinary, and re- dilated third and lateral ventricles, and separated pos- spiratory systems occur as well [2,6,7]. Dysmorphism terior horns of the lateral ventricle. findings such as microcephaly, broad forehead, and In conclusion, rhombencephalosynapsis has vari- superior lip shift down, dysplastic ear, strabismus in ous clinical presentations, as well as characteristic ap- right eye, bilateral pes equinovarus, and hammer toe pearance on magnetic resonance imaging. in both feet have been stated. However system analyses were normal. Survival time of cases are generally Declaration of Conflicting Interests: The authors declare short and they can rarely survive into early adulthood. that they have no conflict of interest. Newly diagnosed cases in the adulthood are extremely rare [1,2,7]. Our patient is four year-old and is healthy Financial Disclosure: No financial support was received. except his mental retardation. REFERENCES Rhombencephalosynapsis occurs in response to a disturbance of development of the cerebellum at 28 1. Chemli J, Abroug M, Kalthoum T, Abdelaziz H. Rhomben- cephalosynapsis diagnosed in childhood: clinical and MRI to 41 days of gestation, a time period consistent with findings. Eur J Paediatr Neurol 2007;11:35-38. the formation of the supratentorial structures found to 2. Toelle S, Yalcinkaya C, Kocer N, et al. Rhombencephalo- be abnormal in patients with RES [1-2]. During nor- synapsis: clinical findings and neuroimaging in 9 children. mal development, the cerebellar hemispheres arise Neuropediatrics 2002;33:209-214. from two distinct embryonic primordia, known as the 3. Shahrzad M, Gold M. Rhombencephalosynapsis: a rare con- rhombic lips. From this perspective, rhombencephalo- genital anomaly presenting with seizure and developmental synapsis is considered to be abnormal development of delay. Acta Neurol Belg 2015;115:685-686. the vermis with subsequent fusion of the hemispheres 4. Passi GR, Bhatnagar S. Rhombencephalosynapsis. Pediatr [5,7]. Most of the cases have been reported in children, Neurol 2015;52:651-652. and almost all cases have been sporadic. Romanengo 5. Arisoy R, Erdogdu E, Pekin O, et al. A rare case of rhombencephalosynapsis and prenatal diagnosis. J Obstet Gynaecol et al. reported on a patient with RES born to consan- 2016;25:1-3. guineous parents and suggested an autosomal reces- 6. Mendonca JLF, Natal MRC, Viana SL, et . Rhomben- sive mode of inheritance, most authors believe that the cephalosynapsis: CT and MRI findings. Neurology India occurrence of RES is sporadic [8]. To date, however, 2004;52:118-120.al no genetic or chromosomal abnormalities and no clear 7. Abdel Razek AA, Castillo M. Magnetic resonance imaging pattern of inheritance have been identified for RES of malformations of midbrain-hindbrain. J Comput Assist [2]. In our case, there is no consanguinity in his parent Tomogr 2016;40:14-25. history. 8. Romanengo M, Tortori-Donati P, Di Rocco M. Rhomben- cephalosynapsis with facial anomalies and probable au- The diagnosis is established with the magnetic tosomal recessive inheritance: a case report. Clin Genet resonance imaging findings. Associated findings on 1997;52:184-186.

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