\documentclass[10pt]{article}

\usepackage{fullpage}
\usepackage{setspace}
\usepackage{parskip}
\usepackage{titlesec}
\usepackage[section]{placeins}
\usepackage{xcolor}
\usepackage{breakcites}
\usepackage{lineno}
\usepackage{hyphenat}





\PassOptionsToPackage{hyphens}{url}
\usepackage[colorlinks = true,
            linkcolor = blue,
            urlcolor  = blue,
            citecolor = blue,
            anchorcolor = blue]{hyperref}
\usepackage{etoolbox}
\makeatletter
\patchcmd\@combinedblfloats{\box\@outputbox}{\unvbox\@outputbox}{}{%
  \errmessage{\noexpand\@combinedblfloats could not be patched}%
}%
\makeatother


\usepackage{natbib}




\renewenvironment{abstract}
  {{\bfseries\noindent{\abstractname}\par\nobreak}\footnotesize}
  {\bigskip}

\titlespacing{\section}{0pt}{*3}{*1}
\titlespacing{\subsection}{0pt}{*2}{*0.5}
\titlespacing{\subsubsection}{0pt}{*1.5}{0pt}


\usepackage{authblk}


\usepackage{graphicx}
\usepackage[space]{grffile}
\usepackage{latexsym}
\usepackage{textcomp}
\usepackage{longtable}
\usepackage{tabulary}
\usepackage{booktabs,array,multirow}
\usepackage{amsfonts,amsmath,amssymb}
\providecommand\citet{\cite}
\providecommand\citep{\cite}
\providecommand\citealt{\cite}
% You can conditionalize code for latexml or normal latex using this.
\newif\iflatexml\latexmlfalse
\providecommand{\tightlist}{\setlength{\itemsep}{0pt}\setlength{\parskip}{0pt}}%

\AtBeginDocument{\DeclareGraphicsExtensions{.pdf,.PDF,.eps,.EPS,.png,.PNG,.tif,.TIF,.jpg,.JPG,.jpeg,.JPEG}}

\usepackage[utf8]{inputenc}
\usepackage[ngerman,greek,english]{babel}



\usepackage{float}








\begin{document}

\title{``Chiari II malformation with Trisomy 18 -- A rare bird}



\author[1]{Sadia Yaqoob}%
\author[1]{Amna Saleem}%
\author[2]{Vikash Jaiswal}%
\author[3]{Samir Ruxmohan}%
\author[4]{Christine Zakhary}%
\affil[1]{Jinnah Medical and Dental College}%
\affil[2]{AMA School of Medicine}%
\affil[3]{Larkin Community Hospital Inc}%
\affil[4]{Ain Shams University Hospital}%


\vspace{-1em}



  
  \date{May 27, 2024}


\begingroup
\let\center\flushleft
\let\endcenter\endflushleft
\maketitle
\endgroup





\selectlanguage{english}
\begin{abstract}
Studies have revealed an association of neural disfigurement with
trisomy 18. Hereby, we report a rare coalition of Trisomy 18 and Arnold
Chiari malformation along with myelomeningocele in a premature neonate.
Despite managing hydrocephalus, the patient' condition deteriorated over
time due to underlying cardiothoracic defects.%
\end{abstract}%



\sloppy


\textbf{Chiari II malformation with Trisomy 18- A rare bird}

Sadia Yaqoob\textsuperscript{1}, Amna Saleem\textsuperscript{1}, Vikash
Jaiswal\textsuperscript{2}, Samir Ruxmohan\textsuperscript{3}, Christine
Zakhary\textsuperscript{4}

\begin{enumerate}
\tightlist
\item
  Jinnah Medical and Dental College, Karachi, Pakistan
\item
  AMA School of Medicine, Philippines
\item
  Department of Neurology, Larkin Community Hospital, South Miami,USA
\item
  Internal Medicine, Ain Shams General Hospital, Cairo, Egypt
\end{enumerate}

Corresponding author:

Sadia Yaqoob

Postal Address: Lady Sughra Begum Building, Flat No.1, Plaza Quarters,
M.A Jinnah Road, Karachi, Pakistan.

Contact: +923334446076

Email: \emph{sadiayaqoob@outlook.com}

ABSTRACT

Studies have revealed an association of neural disfigurement with
trisomy 18. Hereby, we report a rare coalition of Trisomy 18 and Arnold
Chiari malformation along with myelomeningocele in a premature neonate.
Despite managing hydrocephalus, the patient' condition deteriorated over
time due to underlying cardiothoracic defects.

KEYWORDS

Arnold Chiari II Malformation, Trisomy 18, Myelomeningocele,
Hydrocephalus

KEY CLINICAL MESSAGE

Although treating hydrocephalus has proven to be a successful management
option for symptomatic Chiari II disfigurement, but concurrent
illnesses, particularly cardiothoracic defects call for prompt
management to reduce morbidity and mortality.

INTRODUCTION

Trisomy 18 is a rare eugenic aneuploidy with an estimated incidence of
1:3500 to 1:8000 newborns. The fatality rate is massive among these
patients with less than 10\% survival incidence over one
year\textsuperscript{1}. The occurrence of an unwanted additional
genetic material on chromosome number 18 gives rise to myriad of
congenital abnormalities, growth retardation, and prominent cognitive
defects\textsuperscript{2}. Studies have revealed an association of
neural disfigurement with trisomy 18. Hereby, we report a rare coalition
of Trisomy 18 and Arnold Chiari malformation along with
myelomeningocele.

Arnold Chiari Malformation II is the herniation of the hindbrain through
the foramen magnum compressing the cervical spine. Identified based on
cerebral gyration, dysmorphic corpus callosum, and hydrocephalus and
manifesting with symptoms including dysphagia, motor insufficiency, and
stridor, ACM II is believed to be stringently linked with
myelomeningocele\textsuperscript{3, 4}. The frequency of
myelomeningocele varies 0.2 to 2 per 1000 live births that may result in
diverse clinical presentations, including
hydrocephalus\textsuperscript{6}.

The complications arising secondary to myelomeningocele encompass
seizures, learning deficits, cognitive impairment, sensory diminution
below the level of lesion, bowel dysfunction, neurogenic bladder with
recurrent Infection and decreased mobility due to associated muscle
weakness\textsuperscript{6}. Early diagnosis can help in paring down the
severity and subsequently the death rate, further assisting in the
management of such patients.

CASE PRESENTATION

A newborn girl was delivered at 35 weeks by emergency C-section due to
non-reassuring fetal heart rate tracings and intra-uterine growth
restriction. The mother was 39 years old at the time of delivery and had
a past obstetric history of spontaneous abortion of a fetus with Trisomy
22. Prenatal ultrasound revealed polyhydramnios, an atrial septal
defect, a horseshoe kidney, and severe intrauterine growth restriction
(\textless{}1st percentile). The mother had received penicillin for
group B streptococcal infection and corticosteroids for lung maturation
at 30 weeks of gestation.

The patient was diagnosed with Trisomy 18 via non-invasive prenatal
testing (NIPT). She was born after a third pregnancy. Her APGAR scores
were 5 and 8 at 1 and 5 minutes, respectively. Physical examination
revealed dolichocephaly, a prominent occiput, microstomia, nasal
hypoplasia, a short-webbed neck, malformed ears, pectus carinatum, and
clenched fists overlapping fingers, large lumbosacral myelomeningocele,
and talipes equinovarus with rocker-bottom feet. Vital signs were:
weight, 1.45kg; temperature, 100.4\selectlanguage{ngerman}°F; heart rate, 171 beats/ min;
respiratory rate, 52 breaths/ min; blood pressure, 52/84 mmHg; and
oxygen saturation, 100\%. Neurological examination revealed the
spontaneous movement of bilateral upper extremities, no movement and
decreased bulk in the lower extremities, and 2+ reflexes at biceps,
patella, and ankle, with intact cranial nerves and sensation. The rest
of the systemic examination was unremarkable. The anus was patent, and
she passed meconium within the first 24 hours. She was immediately
intubated and placed on synchronized intermittent mandatory ventilation
(SIMV). An orogastric tube (OGT) was attempted, but the tube did not
pass beyond 6 centimeters.

Laboratory profiles, including complete blood picture (CBC), serum urea,
creatinine and electrolytes, and coagulation profile, were routinely
monitored during admission. The test results were unremarkable except
for low platelet count (94x103/\selectlanguage{greek}µ\selectlanguage{english}L) and increased creatinine levels (0.81
mg/dl), observed on the second day of admission, which subsequently
achieved normal limits. Urine output was 3.3 ml/kg/hr. TORCH panel was
negative. Lumbar puncture was performed (opening pressure was not
measured), and cerebrospinal fluid (CSF) appeared red due to traumatic
tap (1000 RBCs to 1 WBC ratio), while the remaining indices were
clinically insignificant. CSF cultures and meningitis/encephalitis panel
PCR were negative. A postnatal karyotype analysis confirmed 47 XX +18,
consistent with the diagnosis of Trisomy 18. On chest x-ray, OGT was
seen in the upper part of the chest and air trapped in the
gastrointestinal tract, which portends to esophageal atresia with a
tracheoesophageal fistula.

The head ultrasound shows crowding of the posterior fossa, effacement of
the fourth ventricle, interdigitation of the gyri along the cerebral
falx, a dysmorphic corpus callosum, and mild to moderate supratentorial
hydrocephalus (Fig.1). These findings were consistent with the diagnosis
of Chiari type II malformation. No signs of intracranial hemorrhage were
evident. An abdominal ultrasound was also performed, showing small
echogenic kidneys with mild right pelvicaliectasis and a large, left
lateral, diaphragmatic focal eventration. A transthoracic echocardiogram
showed a significant ventricular septal defect, tricuspid valve
dysplasia, large patent ductus arteriosus, and a fenestrated patent
foramen ovale which was followed up by the cardiology team.

The patient was strictly NPO, and a low continuous suction tube was
maintained with a Replogle tube. She was managed with palliative care
and empirical antibiotic therapy (ampicillin and gentamicin) until the
surgical closure of open myelomeningocele. The attending doctor
discussed the patient's poor prognosis with parents who expressed
understanding and were coping with their daughter's trajectories. With
the parent's consent, surgical repair of myelomeningocele and
right-frontal reservoir placement for hydrocephalus proceeded which was
well-tolerated. The neurosurgery team continued to follow up. The head
circumference was measured, and CSF analysis via the reservoir was
evaluated daily for six days post-operatively.

The pediatric surgeon was consulted for transesophageal repair,
gastrotomy, and bronchoscopy. Orthopedic surgery consultation was sought
about rocker-bottom feet. The patient was under observation for two
months, but her condition has deteriorated over time due to
cardiothoracic defects.

DISCUSSION

Trisomy 18, often known as Edward syndrome, is an unusual genetic
disease, manifesting as multi-system anomalies. Recognized since 1960,
Trisomy 18 was initially delineated by Edwards and associate as trisomy
17, and concomitantly by Smith and colleagues as trisomy 18. The
appearance of an extra autosome disrupts the stability of the gene
resulting in several developmental oddities\textsuperscript{7}.

Literature reveals that females have a higher probability of embracing
this syndrome with a male to female ratio of 1:3. Moreover, an average
maternal age, typically more than 34.3 years is frequently associated.
In addition, intrauterine growth retardation is an idiosyncratic trait
for this syndrome that follows fetal discomfort leading to high rates of
emergency cesarean section in such conditions. All these elements were
present in our case with maternal age of 39 years and a female baby with
severe IUGR, delivered through an emergency C-Section; hence
corroborating with the findings from past studies\textsuperscript{8}.

Classic associations including acyanotic heart defects, diaphragmatic
eventration, tracheoesophageal fistula, horseshoe-shaped kidney, spina
bifida with myelomeningocele, dolichocephaly, pectus carinatum, clenched
fists with overlapping fingers, and talipes equinovarus with rocker
bottom feet were established as in the past
literature\textsuperscript{2, 9}. However, Arnold Chiari Malformation
type II was the most striking manifestation confirmed on cranial
ultrasound. Ultrasonic features like posterior fossa crowding,
interdigitation of the gyri, dysmorphic corpus callosum, and effacement
of the fourth ventricle along with supratentorial hydrocephalus were
consistent with the findings of a previous study\textsuperscript{4}.

The association of trisomy 18 with Arnold Chiari Malformation is a
rarity with only two published case reports to the best of our knowledge
so far\textsuperscript{4, 8}.\textbf{~} Although growth and evolutionary
inadequacy of CNS can be due to various etiologies, but the threshold
for acquiring several defects is decreased with increasing dysraphism in
trisomy 13. Subsequently, it is also suggested that certain subsidiary
genes causing neural tube defects are located on chromosome 18,
therefore, providing a possible rationale for this
association\textsuperscript{10}.

Chiari II malformation mostly occurs with myelomeningocele, a spinal
rachischisis occurring as a consequence of neural tube defect.
Myelomengiocele is associated with Arnold Chiari malformation and
hydrocephalus in 80-95\% of the cases\textsuperscript{11}. Even though a
small number of studies have promulgated hydrocephalus with trisomy 18,
the rationale was non-significant and without any autopsy
authentication. Mild to moderate supratentorial hydrocephalus was
possibly present in our case secondary to Arnold Chiari malformation as
suggested by ME Case\textsuperscript{4}. Earlier, direct hindbrain
decompression was the mainstay treatment but after recent advancements,
treating hydrocephalus has proven to be a successful management option
and an epitome for curing symptomatic Chiari II disfigurement as done in
our study\textsuperscript{3}.

CONCLUSION

Babies born with trisomy 18 present with a wide array of malformations
including, craniofacial, limb, kidney, cardiac, and neurological
defects. Such complex medical problems can be life-threatening. Albeit,
current technological advancements have enabled prompt diagnosis of
trisomy 18, but management has always been a conundrum due to several
ailments. Arnold Chiari II malformation with concomitant
myelomeningocele is usually associated with trisomy 18. Surgical repair
of myelomeningocele and right-frontal reservoir placement for
hydrocephalus can improve the patient's condition and extend survival.
However, cardiothoracic defects may lead to early mortality.

ACKNOWLEDGEMENTS

We would like to acknowledge the patient and parent's participation and
cooperation in this report.

CONFLICT OF INTEREST

None declared by any of the authors.

AUTHOR CONTRIBUTIONS

Sadia Yaqoob: Involved in data analysis, interpretation, literature
review, drafting and revision of the manuscript.

Amna Saleem: Involved in data analysis, interpretation and drafting of
the manuscript.

Vikash Jaiswal: Involved in data collection and drafting of the
manuscript.

Samir Ruxmohan: Involved in data collection and interpretation, and
final revision of the manuscript.

Christine Zakhary: Involved in data collection and revision of the
manuscript.

ETHICAL STATEMENT

We confirm that the manuscript has been read and approved by all the
authors. Informed consent was obtained from parents of the patient
regarding the publication of case.

REFERENCES

\begin{enumerate}
\tightlist
\item
  Imataka G, Suzumura H, Arisaka O. Clinical features and survival in
  individuals with trisomy 18: A retrospective one-center study of 44
  patients who received intensive care treatments.~\emph{Mol Med Rep} .
  2016;13(3):2457-2466. doi:10.3892/mmr.2016.4806
\item
  Pont SJ, Robbins JM, Bird TM, et al. Congenital malformations among
  liveborn infants with trisomies 18 and 13.~\emph{Am J Med Genet A} .
  2006;140(16):1749-1756. doi:10.1002/ajmg.a.31382
\item
  Kim I, Hopson B, Aban I, et al. Decompression for Chiari malformation
  type II in individuals with myelomeningocele in the National Spina
  Bifida Patient Registry.~\emph{J Neurosurg Pediatr} .
  2018;22(6):652-658. doi:10.3171/2018.5.PEDS18160
\item
  Case ME, Sarnat HB, Monteleone P. Type II Arnold-Chiari malformation
  with normal spine in trisomy 18.~\emph{Acta Neuropathol} .
  1977;37(3):259-262. doi:10.1007/BF00686888
\item
  Naidich TP, McLone DG, Fulling KH. The Chiari II malformation: Part
  IV. The hindbrain deformity.~\emph{Neuroradiology} .
  1983;25(4):179-197. doi:10.1007/BF00540232
\item
  Mummareddy N, Dewan MC, Mercier MR, Naftel RP, Wellons JC 3rd,
  Bonfield CM. Scoliosis in myelomeningocele: epidemiology, management,
  and functional outcome.~\emph{J Neurosurg Pediatr} .
  2017;20(1):99-108. doi:10.3171/2017.2.PEDS16641
\item
  EL-ALFI OS, BIESELE JJ, SMITH PM. TRISOMY 18 IN A HYDROCEPHALIC
  FETUS.~\emph{J Pediatr} . 1964;65:67-70.
  doi:10.1016/s0022-3476(64)80553-9
\item
  Kinoshita M, Nakamura Y, Nakano R, et al. Thirty-one autopsy cases of
  trisomy 18: clinical features and pathological findings.~\emph{Pediatr
  Pathol} . 1989;9(4):445-457. doi:10.3109/15513818909022365
\item
  HOLMAN GH, ERKMAN B, ZACHARIAS DL, KOCK HF. The 18-trisomy
  syndrome-two new clinical variants. One with associated
  tracheoesophageal fistula and the other with probable familial
  occurrence.~\emph{N Engl J Med} . 1963;268:982-988.
  doi:10.1056/NEJM196305022681804
\item
  Flannery DB, Kahler SG. Neural tube defects in trisomy
  18.~\emph{Prenat Diagn} . 1986;6(2):97-99. doi:10.1002/pd.1970060204
\item
  Stein SC, Schut L. Hydrocephalus in myelomeningocele.~\emph{Childs
  Brain} . 1979;5(4):413-419. doi:10.1159/000119836
\end{enumerate}

FIGURES

Figure 1: Cranial ultrasound of neonate showing supratentorial
hydrocephalus and dysmorphic corpus callosum.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

