Scientific Foundation SPIROSKI, Skopje, Republic of Macedonia Open Access Macedonian Journal of Medical Sciences. 2020 Oct 19; 8(C):205-208. https://doi.org/10.3889/oamjms.2020.4806 eISSN: 1857-9655 Category: C - Case Reports Section: Case Report in Pediatrics Characteristics of the Central Nervous System Malformations Presented in Trisomy 13: A single-center Experience in Recognizing the Phenotype and Genotype Ahmad Faried1,2*, Bremmy Laksono2, Danny Halim1, Riksa Parikrama2, Mirna Sobana1, Muhammad Z. Arifin1 1Department of Neurosurgery, Faculty of Medicine, Padjadjaran University (UNPAD), Dr. Hasan Sadikin Hospital (RSHS), Bandung, Indonesia; 2The Center of Genetic Study, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia Abstract Edited by: Igor Spiroski BACKGROUND: Patients who are diagnosed with trisomy 13 (Patau syndrome) are known to have a poor Citation: Faried A, Laksono B, Halim D, Parikrama R, Sobana M, Arifin MZ. Characteristics of the Central prognosis. It has been hypothesized that such poor outcomes are suspected to be attributed to their central nervous Nervous System Malformations Presented in Trisomy 13: system (CNS)-malformations and cardiac-malformations. This study was conducted at Division of Neuropediatric, A Single-center Experience in Recognizing the Phenotype Department of Neurosurgery, Faculty of Medicine, Universitas Padjadjaran – Dr. Hasan Sadikin Hospital, Bandung and Genotype. Open Access Maced J Med Sci. 2020 Oct 19; 8(D):1-4. (2012–2018). https://doi.org/10.3889/oamjms.2020.4806 Keywords: Trisomy 13; central nervous system AIM: This study aimed to describe clinical characteristics and karyotype findings in patients who were diagnosed with malformations; cardiac malformations; cardiopulmonary Patau syndrome and treated at our center. Since Indonesia is still categorized as a lower middle-income country with arrest; severe infection *Correspondence: Ahmad Faried, Department limited resources, we expected that this study would provide a clinical reference on how a congenital disease with of Neurosurgery, Faculty of Medicine, Universitas chromosomal abnormalities is confirmed. Padjadjaran, Dr. Hasan Sadikin Hospital, Jl. Pasteur No. 38, Bandung 40161, West Java, Indonesia. E-mail: [email protected] CASE PRESENTATION: Our cases indicate that CNS malformations are likely to be the cause of indirect mortality of Received: 19-Apr-2020 patients’ early period of life. The median survival in our study is 7 days, while the longest survival is 30 days. The major Revised: 05-Oct-2020 cause of death is apnea, which found in 4 of 5 diagnosed infants. One patient died of severe infection. In most cases, Accepted: 09-Oct-2020 Copyright: © 2020 Ahmad Faried, Bremmy Laksono, where CNS malformations were observed microcephaly with sloping forehead, Dandy–Walker syndrome, lobar or Danny Halim, Riksa Parikrama, Mirna Sobana, alobar holoprosencephaly and ventriculomegaly were identified, as well as neural tube defects (NTDs) were identified, Muhammad Z. Arifin Funding: This study was supported by a grant from The such as spina bifida and meningoencephalocele. CNS malformations, such as holoprosencephaly, may be associated Indonesian Ministry of Research and Technology (16/E1/ with episodes characterized by temporary cessation of spontaneous breathing (apnea) as direct cause of mortality. KPT/2020) for Basic Research Competing Interests: The authors have declared that no CONCLUSION: We conclude that early treatment in Patau syndrome patient in our center should be focused on competing interests exist. Open Access: This is an open-access article distributed more life-threatening problem caused by CNS malformations than NTDs defects, such defects could be managed under the terms of the Creative Commons Attribution- electively. NonCommercial 4.0 International License (CC BY-NC 4.0) Introduction and treating patients with Patau syndrome. This is how we describe our experiences in establishing diagnosis of patients with Patau syndrome. To the Patau syndrome is an incurable congenital best of our knowledge, there is no preceding report disease, characterized by malformation of body parts, regarding the clinical characteristics, and karyotype and impaired intellectual capacities. In the majority of findings in Indonesia, especially in Bandung have ever the cases, karyotyping identifies trisomy of chromosome been released. The aim of this study is to provide an 13. However, a duplication of part(s) of chromosome 13 insight regarding the management of Patau syndrome and mosaicism has also been acknowledged in some from the case series of Patau syndrome at our center. patients, thus resulting in the diversity of phenotypes The correlation of trisomy 13 to this syndrome was of Patau syndrome. Therefore, it is not surprising if first described by Patau et al. in 1960 [1]. Most infants phenotype and karyotype findings in patients who are with Patau syndrome have a high mortality; the median diagnosed with Patau syndrome have kept scientists and clinicians intrigued. In lower- to middle-income survival around 4 days old [2]. Malformations of the countries like Indonesia, diagnosis and treatment of central nervous system (CNS) and cardiac have been congenital diseases such as Patau syndrome are suggested as main attribute of death caused in patients still challenging. Apart from difficulties such as the with Patau syndrome. A thorough study on the clinical unavailability of a medical specialist in clinical genetics characteristics would also be useful to evaluate the and the overwhelming number of patients treated with true cause of death among patients who are diagnosed related specialists on a daily basis, limited resources with Patau syndrome, particularly in patients who were added another layer of challenges in making diagnosis diagnosed and treated at our center. Open Access Maced J Med Sci. 2020 Oct 19; 8(C):205-208. 205 C - Case Reports Case Report in Pediatrics Case Presentation treated in neonatology intensive care unit with poor prognosis; and severe infection as cause of death. This is a case series study performed in a single center: Faculty of Medicine, Universitas Padjadjaran (FK UNPAD) – Dr. Hasan Sadikin Hospital (RSHS), Bandung. Patients suspected of having Patau syndrome were initially admitted to the department of pediatrics or neurology before being consulted to the department of neurosurgery. When necessary, the a b diagnosis was confirmed the cytogenetic examination. Data were collected from patients who were suspected Figure 1: Representative results of karyotyping of Trisomy 13. Chromosomes images obtained from cover slide glass, with three of having Patau syndrome, in the period of 2012– sets of chromosome 13 are shown with arrows (a). Reported 2018. The inclusion criteria were patients with clinical rearrangement of the total chromosomes showed that the patient phenotype of Patau syndrome and having been has a total of 47 chromosomes, including three complete copies of confirmed of having trisomy of chromosome 13. Since chromosome 13 shown in the red circle (b) karyotyping is not covered by our national insurance Patient #3. was born a term from P1A0 mother coverage, not all patients who were suspected with (37–38 weeks of gestation), with Dandy–Walker Patau syndrome could be included in this study. syndrome and seizure; karyotype as 47, XY, +13, and They were around 15 patients suspected with Patau imaging evaluations shown hypoplasia of the vermis, syndrome, which was admitted during the study period; cystic dilatation of the fourth ventricle, and enlarged most clinical examinations reveal as microcephaly, cleft posterior fossa with torcular-lambdoid inversion; lip and palate, and low set ears. Clinical characteristics respiratory failure complications treated in neonatology and karyotype findings were constructed from patients’ intensive care unit with poor prognosis; and apnea as medical record. cause of death. Five patients with Patau syndrome who had their diagnosis confirmed at the period of 2012 to 2018 were included in this study (Table 1): Patient #1. was born a term from P2A1 mother (37–38 weeks of gestation), with multiple congenital anomaly (posterior meningioencephalocele rupture, a b microcephaly, right microphtalmia, immature retina at Figure 2: Identified clinical features showed sloping forehead the left eye, short neck, labiopalatoschisis, and low microcephaly, a broad flat nose, widely set eyes with posterior set ear); karyotype as 47, XY, +13 (Figure 1), and meningioencephalocele rupture, right microphtalmia, absent of imaging evaluations shown a dextrocardia, right lung eyebrows (white arrow), immature retina at the left eye, short neck, dysgenesis, and spina bifida at the corpus of thoracic labiopalatoschisis, abnormal low set of ears (red circle) (a). Radiological vertebra 1, 2, and 3; open wound care as treatment feature showing dextrocardia, right lung dysgenesis, unclear renal contour and spina bifida of corpus vertebra thoracal 1,2,3 (b) for meningioencephalocele rupture with antibiotics therapy for infection occurred and respiratory failure Patient #4. was born aterm from P5A2 complications (Figure 2) treated in neonatology mother (38 weeks of gestation), with microcephaly, intensive care unit with poor prognosis; and apnea as microphthalmia, labiopalatoschisis, and low set ears; cause of death. karyotype as 47, XX, +13, and imaging evaluations shown lobar holoprosencephaly (Figure 3) and Patient #2. was born a term from P1A0 mother (37–38 weeks of gestation);