\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,english]{babel}



\usepackage{float}








\begin{document}

\title{A Rare Case of 2q37 Deletion Syndrome Presented with Patent Foramen
Ovale}



\author[1]{Ahmed  Zaki}%
\author[2]{Nour  Shaheen}%
\author[3]{Abdelraouf  Ramadan}%
\author[4]{Abdelraouf  Ramadan}%
\author[5]{Abdulqadir Nashwan}%
\affil[1]{Cairo University}%
\affil[2]{Alexandria University Faculty of Medicine}%
\affil[3]{Helwan University}%
\affil[4]{University of Louisville}%
\affil[5]{Hamad Medical Corporation}%


\vspace{-1em}



  
  \date{May 26, 2024}


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





\selectlanguage{english}
\begin{abstract}
Here we report a patient with 2q37 deletion syndrome confirmed by
comparative genomic hybridization (CGH) plus single nucleotide
polymorphism (SNP), who does not suffer from mental developmental
abnormalities. The patient, however, does suffer from fatigue and gross
motor delay, and the presence of a patent foramen ovale.%
\end{abstract}%



\sloppy


\textbf{A Rare Case of 2q37 Deletion Syndrome Presented with Patent
Foramen Ovale}

Ahmed Zaki\textsuperscript{1}, Nour Shaheen\textsuperscript{2}, Mohamed
Hosny\textsuperscript{3}, Abdelraouf Ramadan\textsuperscript{4},
Abdulqadir J. Nashwan\textsuperscript{5*}

\begin{enumerate}
\tightlist
\item
  Cairo University, Faculty of Medicine, Cairo, Egypt.
\item
  Alexandria University, Faculty of Medicine, Alexandria, Egypt
\item
  Helwan University, Faculty of Medicine, Cairo, Egypt.
\item
  Louisville University, Kentucky, Louisville, United States.
\item
  Hamad Medical Corporation, Doha, Qatar
\end{enumerate}

\textbf{*Corresponding author:}

Abdulqadir J. Nashwan

anashwan@hamad.qa

Tel: (+974) 40240487

Mob: (+974) 66473549

P.O. Box 3050

Hamad Medical Corporation, Doha, Qatar

\par\null

\textbf{Informed Consent}

Written informed consent was obtained from the patient's legal guardian
to publish this report in accordance with the journal's patient consent
policy.

\textbf{Abstract}

Here we report a patient with 2q37 deletion syndrome confirmed by
comparative genomic hybridization (CGH) plus single nucleotide
polymorphism (SNP), who does not suffer from mental developmental
abnormalities. The patient, however, does suffer from fatigue and gross
motor delay, and the presence of a patent foramen ovale.

\textbf{Key Clinical Message}

2q37 deletion syndrome is associated with mild to severe intellectual
disability, delayed motor skills such as sitting and walking, and
behavioral problems. However, cardiac anomalies are up to 20\% in this
syndrome.

\textbf{Keywords:} 2q37 deletion syndrome; patent foramen ovale; cardiac
Anomalies; chromosome 2; comparative genomic hybridization; single
nucleotide polymorphism

\textbf{Introduction}

2q37 deletion syndrome is a chromosomal condition in which the patient
has lost a small portion of genetic material. The deletion of the 2q37
gene can result in chromosomal breaks in three different bands: 2q37.1,
2q37.2, and 2q37.3. The 2q37 region in the long q arm of chromosome 2 is
divided into three cytogenic areas with a subsequent 179 genes inside
them. However, only 11 genes are related to the 2q37 deletion syndrome.
The lost material is variable and found in one of the patient's 2
chromosome 2s {[}1{]}. The majority of patients with the 2q37
microdeletion syndrome are isolated cases with normal parenteral
phenotype-karyotype {[}2{]}. The patient's development is affected, but
how the patient is affected, or the affection rate varies widely and
even differs for people who lost the same DNA. The usual characteristics
found in babies include low muscle tone and feeding difficulties. Later,
the patient suffers from developmental delay, learning disabilities,
changes in appearance, and low muscle tone. Asthma and ear and chest
infections are common. Seizures occur in some patients. Patients mostly
presented with brachycephaly, obesity, hypotonia, failure to thrive,
seizures, digit abnormalities, and autism. Facial dysmorphia differs
from one to another; any of these features may be present (prominent
forehead, sparse, flared medial eyebrows, depressed nasal bridge,
V-shaped nasal tip, high-arched palate, alopecia totalis, boxy skull
with prominent forehead, up-slanting palpebrae {[}3-4{]}. The 2q37
deletion syndrome can also cause gastrointestinal anomalies, such as
pyloric stenosis {[}5{]}, and central nervous system (CNS) anomalies,
such as holoprosencephaly {[}6{]}. In this case, the cardiological
malformation associated with the 2q37 deletions is apparent. Nearly 20\%
of patients have cardiac anomalies such as ventricular septal defects
and aortic coarctation {[}7{]}. Following an exhausting (English)
literature search, this is the first case with 2q37 deletion syndrome
presented with cardiac anomalies being reported.

\textbf{Case Presentation}

A 3-year-old female child was presented to the clinic with easy
fatigability, gross motor delay, low muscle tone, and flexible pes
planus. The parents have had concerns that she appears to have
difficulty keeping up with kids her age. The patient is otherwise
healthy, growing, and developing normally. The examination was performed
and revealed the following; on general examination, the patient was
pleasant and cooperative. The head was normocephalic with no dysmorphic
features. On the HEENT (head, eyes, ears, nose, and throat) exam, the
oropharynx was clear with moist mucous membranes. The neck was supple. A
cardiovascular exam revealed strong peripheral pulses with a brisk
capillary refill and normal breathing. The abdomen was soft with no
palpable masses. Extremities were warm and well perfused. Observational
gait analysis showed a heel-toe reciprocating gait with no deviations
noted and normal bulk. The tone was mildly reduced throughout. No
tremors or other abnormal movements were noted (Tables 1 \&2).

An echocardiogram was done and revealed a patent foramen ovale (PFO)
with left-to-right shunting (Figure 1). Also, comparative genomic
hybridization (CGH) plus single nucleotide polymorphism (SNP) was
ordered, and the results demonstrated chromosome 2q37 deletion syndrome.
The patient was advised to have 2 sessions and a follow-up
echocardiogram for her abnormal motor delay. After one year of physical
therapy per week, which improved her hypotonia and gross motor delay.

\textbf{Discussion}

2q37 deletion syndrome first appeared in the literature in 1989. Since
then, approximately 74 children and adults have been presented in the
medical literature with 2q37 gene deletion with no additional
chromosomal involvement {[}8{]}. In 2004, US geneticist Dr. Kari Casas
described 66 cases in addition to describing 6 case reports {[}8{]}.

2q37 deletion syndrome is a rare disease that has affected around 100
reported cases worldwide {[}9{]}. The deletion results in developmental
delay, brachydactyly of the third to fifth digits and/or toes, obesity,
short stature, change of facial appearance, and an autism spectrum
disorder {[}3{]}. Patients with deletion syndrome also have some form of
mental retardation {[}10{]}.

We report an American female patient with a 2q37.3 deletion that was
confirmed by comparative genomic hybridization (CGH) plus single
nucleotide polymorphism (SNP). Although clinical presentation is
variable, almost all patients have some degree of mental retardation and
facial dysmorphism. The patient presented with easy fatigability, gross
motor delay, and low muscle tone. An echo was performed, which revealed
a patent foramen ovale with a left-to-right shunt. A cardiovascular exam
found that the heart experienced strong peripheral pulses with a brisk
capillary refill. The patient is otherwise healthy with no dysmorphic
features. The HEENT exam revealed a clear oropharynx with moist mucous
membranes.

Congenital heart defects have been found in around 20\% of patients with
2q37 deletion syndrome. Both septal defects and aortic coarctation have
been described in patients with 2q37 deletion syndrome {[}3{]}. The
patient presented does not have aortic coarctation but does suffer from
the presence of a patent foramen ovale in the atrial septum, which was
confirmed using an echo. The ascending aorta, transverse arch, and
descending aorta were also found to be wide open and not blocking blood
flow.

The patient is growing and developing normally, both physically and
mentally. Growth hormone deficiency has been found in 4 patients with
2q37 gene mutations, which led to short stature. All 4 patients
experienced improved growth following growth hormone administration
{[}11-13{]}.

The better status of the patient who presented with no mental or
physical developmental abnormalities or delays can be attributed to the
size of the deletion. The patient had a gene deletion size of 2.63 MB.
The largest deletion is 10 MB; most are usually greater than 3 MB
{[}14{]}. Almost 30\% of patients with 2q37 deletion syndrome have major
malformations. These generally include the gastrointestinal, nervous
system, and cardiac abnormalities {[}3{]}.

\textbf{Conclusions}

2q37 deletion syndrome is a rare disease that has affected around 100
reported cases worldwide. The deletion results in developmental delay,
brachydactyly of the third to fifth digits and/or toes, obesity, short
stature, change of facial appearance, and an autism spectrum disorder.
In our report, we have reported a very rare case with 2q37 deletion
syndrome confirmed by comparative genomic hybridization (CGH) plus
single nucleotide polymorphism (SNP) that presented with unusual cardiac
anomalies (patent foramen ovale with a left to right shunting). However,
on follow-up, the patient showed improvement with the physical therapy.

\textbf{Declarations}

\textbf{Ethics approval and consent to participate}

The article describes a case report. Therefore, no additional permission
from our Ethics Committee was required.

\textbf{Availability of data and material}

All data generated or analyzed during this study are included in this
published article.

\textbf{Competing interests}

The authors declare that they have no competing interests.

\textbf{Funding}

This study was not funded.

\textbf{Authors' contributions}

Ahmed Zaki, Nour Shaheen, Mohamed Hosny, Abdelraouf Ramadan, Abdulqadir
J. Nashwan: Data Collection, Literature Search, Manuscript Preparation

All authors read and approved the final manuscript

\textbf{Acknowledgments}

Open Access funding provided by the Qatar National Library.

\textbf{References}

\begin{enumerate}
\tightlist
\item
  Leroy C, Landais E, Briault S, et al.: The 2q37-deletion syndrome: an
  update of the clinical spectrum including overweight, brachydactyly
  and behavioural features in 14 new patients. Eur J Hum Genet. 2013,
  21:602-612. 10.1038/ejhg.2012.230
\item
  Doherty ES, Lacbawan FL: 2q37 Microdeletion Syndrome . GeneReviews\selectlanguage{ngerman}®.
  University of Washington, Seattle; 2013. 10.32388/cap641
\item
  Falk RE, Casas KA: Chromosome 2q37 deletion: clinical and molecular
  aspects. Am J Med Genet . 2007, 145:357-71. 10.1002/AJMG.C.30153
\item
  Drake KM, Ruteshouser EC, Natrajan R, et al.: Loss of heterozygosity
  at 2q37 in sporadic Wilms tumor: a putative role for miR-562. Clin
  Cancer Res. 2009, 15:5985. 10.1158/1078-0432.CCR-09-1065
\item
  Lin SP, Petty EM, Gibson LH, Inserra J, Seashore MR, Yang-Feng TL:
  Smallest terminal deletion of the long arm of chromosome 2 in a mildly
  affected boy. Am J Med Genet . 1992, 44:500-2. 10.1002/AJMG.1320440424
\item
  Chassaing N, De Mas P, Tauber M, et al.: Molecular characterization of
  a cryptic 2q37 deletion in a patient with Albright hereditary
  osteodystrophy-like phenotype. Am J Med Genet A. 2004, 128:410-3.
  10.1002/AJMG.A.30199
\item
  Leroy C, Landais E, Briault S, et al.: The 2q37-deletion syndrome: an
  update of the clinical spectrum including overweight, brachydactyly
  and behavioural features in 14 new patients. Eur J Hum Genet. 2013,
  21:602-12. 10.1038/EJHG.2012.230
\item
  Casas KA, Mononen TK, Mikail CN, et al.: Chromosome 2q terminal
  deletion report of 6 new patients and review of phenotype-breakpoint
  correlations in 66 individuals. Am J Med Genet A. 2004, 130:331-9.
  10.1002/AJMG.A.30156
\item
  2q37 deletion syndrome - About the Disease - Genetic and Rare Diseases
  Information Center. Accessed: September 10, 2022.
  https://rarediseases.info.nih.gov/diseases/10202/2q37-deletion-syndrome..
\item
  Kitsiou-Tzeli S, Sismani C, Ioannides M, et al.: Array-CGH analysis
  and clinical description of 2q37.3 de novo subtelomeric deletion. Eur
  J Med Genet. 2007, 50:73-8. 10.1016/J.EJMG.2006.09.004
\item
  Wilson LC, Leverton K, Luttikhuis MEMO, et al.: Brachydactyly and
  Mental Retardation: An Albright Hereditary Osteodystrophy-like
  Syndrome Localized to 2q37. Am J Hum Genet. 1995, 56:400.
\item
  Vetro A, Pagani S, Silengo M, et al.: Severe growth hormone deficiency
  and pituitary malformation in a patient with chromosome 2p25
  duplication and 2q37 deletion. Mol Cytogenet. 2014, 7:..
  10.1186/1755-8166-7-41
\item
  Cho E-K, Kim J, Yang A, Cho SY, Jin D-K: 2q37 Deletion syndrome
  confirmed by high-resolution cytogenetic analysis. Ann Pediatr
  Endocrinol Metab. 2017, 22:129-10. 10.6065/apem.2017.22.2.129
\item
  Aldred MA, Sanford ROC, Thomas NS, et al.: Molecular analysis of 20
  patients with 2q37.3 monosomy: definition of minimum deletion
  intervals for key phenotypes. J Med Genet. 2004, 41:433-9.
  10.1136/JMG.2003.017202
\end{enumerate}

\textbf{Tables \& Figures:}

Figure 1: Echocardiography shows patent PFO

Levocardia, Situs solitus, normal intracardiac anatomy, patent foramen
ovale (PFO) 3 mm with a left to right shunting, Qualitatively Normal
right ventricular size and systolic function, Normal left ventricular
size and systolic function, and no evidence of significant pericardial
effusion.\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
Vital signs & Value\tabularnewline
\midrule
\endhead
Temperature & 36.4 C\tabularnewline
Height & 38.1 inches (96.8 cm)\tabularnewline
Weight & 15.3 kg\tabularnewline
BMI & 16.37 kg/m\selectlanguage{ngerman}²\tabularnewline
\bottomrule
\end{longtable}\selectlanguage{ngerman}

\textbf{Table~1: Vital signs of the presented case}

BMI:~Body Mass Index\selectlanguage{english}
\begin{longtable}[]{@{}lll@{}}
\toprule
Lab results & Value & Reference Range\tabularnewline
\midrule
\endhead
TSH & 1.4 & 0.7 - 6.6 m(iu)/L\tabularnewline
CK & 69 & \textless{} 250U/L\tabularnewline
Calcium & 10.7 & 8.8-10.8 mg/dL\tabularnewline
Potassium & 4.5 & 3.5 -5 mmol/L\tabularnewline
Creatinine & 0.31 & 0.20 -0.43 mg/dl\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table~2: Laboratory results of the presented case}

TSH: Thyroid Stimulating Hormone; CK: Creatine Kinase\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Echonew/Echonew}

\end{center}
\end{figure}

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

