The Differential Diagnosis of a Patient with
Unilateral Congenital Facial Paralysis: 3q21
Nagehan Aslan, MD1, Cigdem Sıvrıce, MD2 and Ahmet Rifat Ormecı, MD3
1Department of Pediatrics, Cukurova University, Turkey
2 Department of Pediatrics, Mustafa Kalemli State Hospital, Turkey
3 Department of Pediatrics, Suleyman Demire l University, Turkey
Submission: September 19, 2017; Published: January 19, 2018
*Corresponding author: Nagehan Aslan, epartment of Pediatrics, Cukurova University, Faculty of Medicine, Turkey.
How to cite this article:Nagehan A, MD, Cigdem S, MD, Ahmet R O, MD. The Differential Diagnosis of a Patient with Unilateral Congenital Facial
Paralysis: 3q21 Deletion. Acad J Ped Neonatol. 2018; 6(3): 555743. DOI: 10.19080/AJPN.2018.06.555743
A 1-year-old female with unilaterally congenital weakness in the facial muscles was referred to us and we have studied the literature about facial paralysis for differantial diagnosis in the light of this case. There are several described causes of facial nerve paralysis in children, as it can be congenital (due to delivery traumas and genetic or malformative diseases) or acquired (due to infective, inflammatory, neoplastic, traumatic or iatrogenic causes) and can be unilaterally or bilaterally. Nonetheless, in approximately 40%-75% of the cases, the cause of unilateral facial paralysis still unknown and remains idiopathic. The differential diagnosis of CFP should include Moebius syndrome, hereditary congenital facial paralysis (HCFP), and congenital ptosis. Herein we describe a patient that presented with unilateral CFP; in addition, the differential diagnosis of CFP and genetic analysis are discussed in the light of the relevant literature.
Pediatric facial nerve paralysis can be congenital or acquired. Congenital facial paralysis (CFP) originates from a structural defect in the facial nerve nucleus and/or cranial nerve, and is often associated with partial or complete absence of the facial nerve. CFP can occur unilaterally or bilaterally. Hereditary congenital facial palsy and Moebius syndrome is considered in the differential diagnosis. Moebius syndrome (MBS) is a rare congenital disorder characterized by facial palsy with limited gaze abduction due to abducens paralysis. Hereditary congenital facial palsy (HCFP) is an autosomal dominant congenital dysinnervation syndrome, recognizable by the isolated dysfunction of the seventh cranial nerve. In this case report we offered a pediatric patient with unilateral CFP and we want to draw attention to the importance of genetic analysis.
A 1-year old female presented with the inability to close her right eye and the left corner of her mouth moving downwards when crying, both of which were present since birth. The G2A1P1Y1 infant weighed 2800 g at birth and was born full-term via normal spontaneous vaginal delivery to a 20-year old mother. The patient’s parents were not consanguineous and the mother reported a negative history of medication use during the pregnancy. Physical examination showed hypertelorism and right
facial paralysis (Figure 1). There weren’t any cardiac or extremity anomalies. Comprehensive laryngoscopic examination was negative for vocal cord paralysis. Hearing test, routine laboratory tests, and abdominal ultrasonography findings were normal.
Ophthalmological examination showed dacryostenosis and ectropion, and the patient was scheduled for surgery. Cranial MRI was negative for structural abnormality of the brain and brain stem. Temporal bone CT showed relatively slight right facial
nerve symmetry (Figure 2). Karyotype analysis was negative for
numerical and structural anomalies. As the patient had isolated
facial paralysis, there weren’t any phenotype characteristics
or concomitant dysmorphic findings, cranial MRI showed no
structural abnormality in the brain and brain stem, Moebius
syndrome was eliminated from the differential diagnosis and CFP
was considered. Genetic analysis was performed using the CGH
array method, which showed an 1867 deletion in 3q21.1q21.2
locations in the region, including the genes SEC22A, ADCY5, MYLK,
ROPN1, UMPS, MUC13, PTPLB, CCDC14, KALRN, ITGB5, HEG1, and
SLC12A8. In order to determine if the patient acquired CFP via
hereditary transmission the parents were referred for genetic
testing. The test detected normally
CFP is characterized by abnormal eye, eyelid, and facial
movements, and the most common cause is perinatal trauma .
The most frequently reported risk factors associated with CFP
are being the firstborn child, birthweight>3500g, use of forceps
during delivery, caesarean delivery, and prematurity. CFP can be
hereditary or sporadic. The parents of the presented case were
referred for genetic testing to determine if hereditary transmission
Moebius syndrome is the primary consideration in the
differential diagnosis of CFP. Previously, CFP was accepted to be
a variant of Moebius syndrome, but recent studies have shown
that CFP and Moebius syndrome are two distinct diseases .
Moebius syndrome is characterized byabducens paralysis and
other systemic abnormalities, in addition to facial nerve paralysis.
In the majority of cases Moebius syndrome is a congenital defect
involving the 6th and 7th cranial nerves bilaterally, and occasionally
unilaterally , whereas less frequently, the 3rd, 4th, 5th, and 9th
cranial nerves are involved.
Musculoskeletal system abnormalities are the primary
additional systemic anomalies accompanying Moebius syndrome
[4-6], although cardiac anomalies, ocular anomalies, and
craniofacial anomalies can be seen. The presented case had
ectropion and dacryostenosis, which were surgically corrected
by the ophthalmology department. The patient also had
hypertelorism, but laryngoscopic examination was normal. As
Moebius syndrome is rarely seen and its etiopathogenesis is not
fully known, the underlying pathological process remains to be
fully understood . When considered as a whole, a localized
developmental defect in the brain stem complex forms the basis of
the pathogenesis of Moebius syndrome . In addition to sporadic
cases of Moebius syndrome, familial cases of autosomal recessive,
autosomal dominant, and X-related recessive transmission have
been reported . Radiological imaging in patients with Moebius
syndrome shows inferior brain stem hypoplasia, a hypoplastic
cerebellum, focal necrosis/calcifications of the central nerve
nuclei, and flattening of the fourth ventricle layer . In the
presented case cranial MRI showed the absence of structural
anomalies in the brain and brain stem.
Genetic analysis is important in the differential diagnosis of
CFP. In cases of unilateral and bilateral CFP, microarray analysis
is recommended for findings deletions that are not found via
chromosome analysis. Peripheral karyotype analysis in the
presented case was normal, whereas via the CGH array method
a microdeletion was found in the 3q21.1q21.2 location. Genetic
analysis of Moebius syndrome patients shows that the 13q12-q13
band region (especially microdeletions in FG9, GSH1, and CDX2) is
primarily responsible for the disease .
Some studies have reported that de novo mutations in
PLXND1 and REV3L cause Moebius syndrome . Moreover, an
association between HCFP, and 3q21.2-q22.1 and 10q21.3-q22.1
chromosome locations has been observed [13,14]; however, at
the time these studies were conducted HCFP was considered a
variant of Moebius syndrome and the researchers associated
these locations with Moebius syndrome. A microdeletion was
noted in the 3q21.1q21.2 location in the presented case and
genetic analysis of the parentsis expected to indicate hereditary
transmission of CFP.
In conclusion, CFP and Moebius syndrome must be carefully
differentiated. Moreover, genetic analysis of CFP patients and
identification of novel associated genes are of critical importance.