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\begin{document}

\title{A Rare Case of Pycnodysostosis during Pregnancy: The First Case from
Oman}



\author[1]{Aisha  Alshdefat}%
\author[2]{Abdulqadir Nashwan}%
\author[3]{Hayat  Al Bibi}%
\affil[1]{Sultan Qaboos University}%
\affil[2]{Hamad Medical Corporation}%
\affil[3]{Yarmouk University}%


\vspace{-1em}



  
  \date{May 19, 2024}


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\selectlanguage{english}
\begin{abstract}
We describe a case in which a 41-year-old pregnant female with
pycnodysostosis presented for elective cesarean section at week 37 + 5
of pregnancy. To the author's best knowledge, this is the first reported
case of pycnodysostosis during pregnancy in Oman.%
\end{abstract}%



\sloppy


\subsection*{Running head: Pycnodysostosis during
Pregnancy}

{\label{running-head-pycnodysostosis-during-pregnancy}}

\subsection*{A Rare Case of Pycnodysostosis during Pregnancy: The First
Case from
Oman}

{\label{a-rare-case-of-pycnodysostosis-during-pregnancy-the-first-case-from-oman}}

\textbf{Aisha Alshdefat\textsuperscript{1}, Abdulqadir
Nashwan\textsuperscript{2}, Hayat Al Bibi\textsuperscript{3}}

\textsuperscript{1} Department of Maternal and Child Health, College of
Nursing, Sultan Qaboos University, Sultanate of Oman, Email:
Alshdefat@squ.edu.om, Office No: +968 24145477, Mobile: + 968 72276413

\textsuperscript{2} Nursing Department, Hamad Medical Corporation, Doha,
Qatar. anashwan@hamad.qa

\textsuperscript{3} Al Yarmouk University, Irbid, Jordan, Email:
hayatbb20000@gmail.com Mobile: +962798507631

\textbf{Corresponding author:}

Mr. Abdulqadir J. Nashwan

anashwan@hamad.qa Tel: (+974) 40240487

Mob: (+974) 66473549 P.O.Box 3050

Hamad Medical Corporation, Doha, Qatar

\textbf{Abstract}

We describe a case in which a 41-year-old pregnant female with
pycnodysostosis presented for elective cesarean section at week 37 + 5
of pregnancy. To the author's best knowledge, this is the first reported
case of pycnodysostosis during pregnancy in Oman.

\textbf{Clinical Key Message}

The authors urge clinicians to diagnose cases with pycnodysostosis
early, especially during pregnancy. The characteristics of
pycnodysostosis may make anesthesia management more challenging.

\emph{\textbf{Keywords:} Pycnodysostosis; defective gene; lysosomal
storage disease; cathepsin K; Dwarfisms}

\textbf{Introduction}

Maroteaux and Lamy defined a clinical condition known as pycnodysostosis
for the first time in 1962. Toulouse-Lautrec syndrome was named after
the French artist Henri de Toulouse-Lautrec, who (it is believed) had
the disorder. The faulty gene for pycnodysostosis was found in 1996. (1)

Discovering the faulty gene that causes pycnodysostosis allows for more
accurate diagnosis, carrier testing, and knowledge of the illness. It is
an autosomal recessive osteochondrodysplasic disorder that is often
identified in childhood. It is a bone lysosomal storage disorder caused
by mutations in the gene encoding the enzyme cathepsin K on chromosome
1, with an estimated frequency of 1--3 per 1,000,000 people. (2) Here,
we describe a case in which a pregnant female with pycnodysostosis
presented for elective cesarean section.

\textbf{Case Presentation}

The patient was a 41-year-old, gravida 3 with pycnodysostosis scheduled
for an elective cesarean delivery at week 37 + 5 of pregnancy. Previous
2 cesarean sections were done, trying with her spinal anesthesia, but
the patient was not cooperative due to labor pain converted to general
anesthesia. General anesthesia was difficult during intubation and
post-extubation; the patient developed aspiration pneumonia and was
managed with antibiotics without admission to the ICU.

The patient was 140 cm in height, weighed 60kg, and had a Body Mass
Index (BMI) of 35.9. she is characterized by a short neck, small
mandible, and Mallampati classification (MPC), TMD thyromental distance.
She had known allergies to Butamirate\selectlanguage{ngerman}® (cough suppressant) and Rhinopro®
(Pseudoephedrine \& Carbinoxamine) drugs and was not taking any
prescription medications.

She had a history of the bilateral femur pathological fractures
(Figure-1) and underwent closed reduction and intramedullary (nail) left
femur early in 2020, under spinal anesthesia Ultrasound showed three
hyperechoic subcutaneous lesions 19x7mm in the post aspect, 12x7mm, and
16x10mm in the medial aspect of the right side. Moreover, the left side
showed four well-defined hyperechoic subcutaneous lesions measuring
20x12mm in the lateral aspect, 10x7mm in the medial aspect, 12x9mm, and
9x6 mm in the posterior aspect. All show no septation, no calcification,
and no vascular by doppler.

She planned for a second surgery for the right femur, but it was not
done because of the COVID-19 pandemic, and after that, she became
pregnant. The patient had severe Obstructive sleep apnea (AH1) diagnosed
by a sleep study in 2014 and mild asthma since childhood advice to be on
continuous positive airway pressure (CPAP), but she refused. The
presence of obstructive sleep apnea may have a risk of airway
obstruction in the postoperative period; thus, it should be carefully
addressed. She had a family history of the same disease in maternal and
paternal cousins (familial), dwarfism, her sister, and her maternal
grandmother.

Physical examination of the spine revealed multilevel disc dehydration;
multiple disc bulges are identified at multiple levels starting in the
cervical and lumbar spine. The most marked changes are seen at the C5-C6
level, where there are left posterior disc bulges causing indentation
over the thecal sac with mild narrowing of the central canal (Figure-3).

On the 1\textsuperscript{st}-day post-Lower Segment Caesarean
section(LSCS), she developed a cough, palpitation, and tachycardia; the
patient desaturated Oxygen demand gradually increased from 3 liters to 8
liters, then she had sustained cardiac arrest, CPR was performed for 2
minutes, with 1 dose of adrenaline, developed later to multiple comorbid
Cardiac arrests was resuscitated and intubated for 4 days, then
extubated and shifted to the inpatient ward.

Later, she developed multi myoclonus jerking, both upper arm spasms with
upward rolling of eyes due to PAID syndrome during her ICU stay. In ICU,
ECG showed sinus tachycardia, T wave inversion in leads V1, V2, V3, V4,
previous ECG dated back to 2022 showed T wave inversions in leads V1,
V2. At the return of spontaneous circulation (ROSC), an arterial blood
gas shows PCO2:70, after 10 minutes of intubation and ambobaging.
Repeated ABG showed lactate: 2.4, PCO2: 45, PO2:65 ON 50\% FIO2. EEG
shows no intracranial mass effect, hemorrhage, or gross ischemic
infarction area.

EEG is indicative of paroxysmal nonepileptic events and a mild-moderate
diffuse encephalopathy secondary to sedative medications. Few lower
extremity jerks were induced only with stimulation recorded with no EEG
correlates. MRI whole spine revealed multi-disc disease but no abnormal
signal in the cord, no major pathology. She was currently admitted under
the impression of post-hypoxic cortical myoclonus.

Computed tomography arterial portography (CTAP) reported bilateral lower
lobes consolidation, more on the left side. Bilateral lung changes could
be related to atelectasis.

The patient complains of adjustment disorder due to physiological
consequences of the current health changes following her delivery as
manifested with low mood; the patient denied that; however, there were
episodes last week in which she was angry, shouting, and refusing
medical care but not anymore. The psychiatrist recommended no need for
psychotropic medication. However, it is important to reassure and
involve her in any intervention and procedure frequently.

The patient shifted to a private room accompanying her newborn and
reports improvement regarding her myoclonic movements, affecting her
lower limb mainly occur whenever she takes her clonazepam and worsens
during evening time (in between the doses). She was unable to sit
without support, unable to mobilize, and difficult to hold her legs in
flexed posture or against gravity due to myoclonus. The patient still
has an involuntary movement of the lower part of the body. On the other
hand, she is alert and oriented with comprehensive speech. The discharge
plan includes a wheelchair with a Zimmer frame, a home CPAP machine, and
home exercises' instructions; the physiotherapist advised not to
discharge the patient and keep her at the hospital.

\textbf{Discussion}

Pycnodysostosis is a rare genetic disorder associated with short limbs,
an obtuse mandibular angle and delayed closure of the cranial sutures.
Some individuals also have dental and nail anomalies. Intelligence is
usually normal, with only minor psychomotor impairments. These
characteristics may make anesthesia management more difficult. (3) Both
sexes are equally affected by the disorder. It is caused by mutations in
the gene cathepsin K located on chromosome 1, with an estimated
prevalence of 1--3 per 1,000,000. (4)

Pycnodysostosis is caused by a gene that was not discovered until 1995
when relevance analysis studies found on chromosome 1q21, which causes a
mutation in cathepsin K, a lysosomal cysteine protease that is highly
expressed in osteoclasts, leading to osteosclerosis and impaired bone
resorption. (5)

Scoliosis, kyphosis, and lumbar hyperlordosis are spine features of
pycnodysostosis. (6) Our patient had spine revealed multilevel disc
dehydration; multiple disc bulges are identified at multiple levels
starting in the cervical and lumbar spine. The most marked changes are
seen at the C5-C6 level, where there are left posterior disc bulges
causing indentation over the thecal sac with mild narrowing of the
central canal (Figure-4). Our patient underwent general anesthesia,
though many researchers recommended performing the cesarean section for
patients with pycnodysostosis under neuraxial anesthesia. (7)

In summary, we present a case of a pycnodysostosis patient having
elective cesarean birth under general anesthesia, who had a cardiac
arrest after the operation, resuscitated for 4 days then extubated and
shifted to the intensive care unit; later on, she developed Myoclonus
jerking impression of the EEG indicative of paroxysmal nonepileptic
events and mild-moderate diffuse encephalopathy secondary to sedative
medication. Few lower extremity jerks were induced only with stimulation
recorded with no EEG correlates. Currently, the patient discharged with
CPAP is recommended to follow up with the physiotherapist and
psychiatrist.

\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{Consent for publication}

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

\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}

AA was involved in the conception and design, the drafting of the paper.

AJN \& HAB were involved in the data collection, revising it critically
for intellectual content; and the final approval of the version to be
published.

All authors agree to be accountable for all aspects of the work.

\textbf{Acknowledgments}

Open Access funding provided by the Qatar National Library.

\textbf{Figure Legends}

Figure-1 bilateral femur X-Ray showing bilateral femur pathological
fractures- closed reduction of the left femur

Figure-2 Left Shoulder X-Ray AP Coracoid process shows fracture

Figure-3 Chest X-Ray shows endotracheal tube, right fracture at midshaft

\textbf{References}

1. Mujawar Q, Naganoor R, Patil H, Thobbi AN, Ukkali S, Malagi N.
Pycnodysostosis with unusual findings: a case report. Cases Journal.
2009;2(1):1-4.

2. Puri R, Saxena A, Mittal A, Arshad Z, Dwivedi Y, Chand T, et al.
Pycnodysostosis: an anaesthetic approach to this rare genetic disorder.
Case Reports in Anesthesiology. 2013;2013.

3. LeBlanc S, Savarirayan R. Pycnodysostosis. 2020.

4. Hansen NS, Dalgaard KS, Jensen TB. Anaesthetic Considerations in a
Patient with Pycnodysostosis undergoing Caesarean Delivery. Case Reports
in Anesthesiology. 2018;2018.

5. Turan S. Current research on pycnodysostosis. Intractable \& rare
diseases research. 2014;3(3):91-3.

6. Beguiristain J, Arriola F, Leyes M. Lumbar spine anomalies in a
pycnodysostosis case. European Spine Journal. 1995;4(5):320-1.

7. Apfelbaum JL, Hawkins JL, Agarkar M, Bucklin BA, Connis RT, Gambling
DR, et al. Practice guidelines for obstetric anesthesia: an updated
report by the American Society of Anesthesiologists Task Force on
obstetric anesthesia and the Society for Obstetric Anesthesia and
Perinatology\selectlanguage{english}*. Anesthesiology. 2016;124(2):270-300.

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