Mobius Syndrome is a rare syndrome with undefined incidence in the United States. In 2003, an estimated 4 out of 189,000 births in Holland were affected [
Clubfoot has been identified as the most common orthopedic association of Mobius Syndrome; congenital hand differences and Poland’s Syndrome are also present in higher frequency. Facioscapulohumeral muscular dystrophy has been associated with Mobius Syndrome and is a progressive proximal muscle disease leading to progressive weakness about the hip and shoulder [
A consistent etiology for the condition has not been definitively identified; however, multiple contributing factors have been described in the literature, including chromosomal abnormalities secondary to teratogenic exposure [
Familial patterns have also been identified but do not appear to contribute to a majority of cases [
In an effort to improve the understanding of the orthopedic associations of Mobius Syndrome, we distributed a survey to the membership of the Mobius Syndrome Foundation after IRB approval had been obtained. The survey included questions regarding the upper extremity, lower extremity, and spine as well as anesthetic and airway concerns. The survey was distributed through the Mobius Syndrome Foundation Newsletter and social media site, and anonymous responses were collected through an established survey website.
Survey responses were tabulated in spreadsheet format and analyzed. Questions were designed as yes and no answers, with an option to further describe or clarify responses as individuals saw fit.
In addition, 23 individuals with Mobius Syndrome were interviewed and examined by the primary author at the Mobius Syndrome Foundation meeting in July 2014. Each patient received a full history, orthopedic exam, and review of any available imaging.
Twenty-three individuals with Mobius Syndrome were examined at the Mobius Syndrome Foundation meeting in July 2014. Age range was 6 months to 64 years, with 15 females and 8 males. Data is summarized in Tables
Patient series results.
Patient | Age | M/F | Clubfoot | Surg. | Revision/# | Foot, other | Pes planovalgus | Transverse deficiency | Hip dysplasia | Hip Surg. |
---|---|---|---|---|---|---|---|---|---|---|
1 | 16 | F | R | R | ||||||
2 | 7 | F | B | B | Bx1 | |||||
3 | 8 | M | L (ankle) | |||||||
4 | 2 | F | ||||||||
5 | 64 | F | ||||||||
6 | 60 | F | L | |||||||
7 | 11 | F | B | |||||||
8 | 7 | M | B | Y | Bx1 | |||||
9 | 27 | F | ||||||||
10 | 6 | M | B | B | Bx2 | |||||
11 | 2 | F | B | B | B Splatt | |||||
12 | 0.5 | F | ||||||||
13 | 3 | M | L | L | Pending | |||||
14 | 1 | M | ||||||||
15 | 22 | F | B | B | Bx1 | |||||
16 | 2.6 | F | B | |||||||
17 | 1 | M | R | Y | N | |||||
18 | 19 | F | B | B | Lx2 | |||||
19 | 13 | F | Small 5th toe | B | ||||||
20 | 3 | M | B | |||||||
21 | 2 | F | Absent P2 1st ray | |||||||
22 | 1 | M | B | Y | N | |||||
23 | 41 | F | ||||||||
% | 60.9% | 34.8% | 30.4% | 8.7% | 4.3% | 4.3% | 8.7% | 8.7% |
Age (years), M/F: male/female, Surg.: surgical treatment, B: bilateral, R: right, L: left, x-#: number of revisions, and Hip Surg.: hip surgery.
Patient series contiued.
Patient | Age | M/F | Scoli. (xr) | Adams | Poland’s | Hand | Side | Surg. | Revision/# |
---|---|---|---|---|---|---|---|---|---|
1 | 16 | F | R thoracic | ||||||
2 | 7 | F | 1-2 cases of webspace syndactyly | R | R | ||||
3 | 8 | M | Polysyndactyly | B | B | Pending | |||
4 | 2 | F | |||||||
5 | 64 | F | |||||||
6 | 60 | F | |||||||
7 | 11 | F | |||||||
8 | 7 | M | Y | R thoracic | |||||
9 | 27 | F | Y | R thoracic, L lumbar | |||||
10 | 6 | N | R | ||||||
11 | 2 | F | |||||||
12 | 0.5 | F | |||||||
13 | 3 | M | |||||||
14 | 1 | M | |||||||
15 | 22 | F | R thoracic | ||||||
16 | 2.6 | F | R | Small hand | |||||
17 | 1 | M | |||||||
18 | 19 | F | Y | R thoracic/L lumbar | |||||
19 | 13 | F | Small 5th finger w/o nail | B | |||||
20 | 3 | M | |||||||
21 | 2 | F | |||||||
22 | 1 | M | R | Small hand | R | ||||
23 | 41 | F | R thoracic | R | Syndactyly s/p release | R | |||
% | 13.0% | 26.1% | 17.4% | 26.1% | 21.7% | 8.7% | 4.3% |
Age (years), M/F: male/female, Scoli. (xr): scoliosis confirmed by radiography, R: right, L: left, and B: bilateral.
Transverse deficiency of the left lower extremity in Mobius Syndrome (anterior view).
View from posterior of transverse deficiency.
Clubfoot status after revision surgery with recurrent deformity, posterior view.
Clubfoot status after revision surgery with recurrent deformity, anterior view.
Four cases of Poland’s Syndrome were identified based on absence of the pectoralis tendon in the axillary fold. One had no hand abnormality, one had a smaller hand compared to the contralateral side, one had a distal transverse deficiency of the small finger, and one had syndactyly status after release. All were on the right side. For Poland Syndrome, one was between the thumb and index finger and responded well to release. The second was a bilateral polysynactyly that had undergone multiple release at the age of 8 months and subsequently recurred.
Five individuals had abnormal Adams forward bending tests, which is a sensitive test for scoliosis. The presence of asymmetry on this test is indicative of possible scoliosis and is used in the screening exam for scoliosis [
All families of children reported “low tone” during the neonatal period, and the majority had delayed motor milestones with ambulation at approximately 2 years. One individual had bilateral hip dysplasia successfully treated with Pavlik Harness.
One hundred and forty-six patients initiated the survey from May 11, 2013, to January 22, 2014. One hundred and nine completed at least some of the questions, although only ninety-six of these patients fully completed the survey. Only the fully completed surveys from the one ninety-six respondents are included in the analysis. Data is summarized in Table
Patient survey results.
Number | Percent | |
---|---|---|
Difference in digital anatomy | 35 | 36.5% |
Syndactyly | 17 | 17.7% |
Upper extremity nerve deficit | 28 | 29.2% |
|
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Difference in digital anatomy | 17 | 17.7% |
Syndactyly | 6 | 6.3% |
Clubfoot | 40 | 41.7% |
Congenital vertical talus | 3 | 3.1% |
Planovalgus foot | 37 | 38.5% |
|
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Missing/weak pectoralis | 29 | 30.2% |
Missing/weak back musculature | 14 | 14.6% |
Sternal abnormality | 23 | 24.0% |
|
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Scoliosis | 27 | 28.1% |
Kyphosis | 10 | 10.4% |
Lordosis | 5 | 5.2% |
Missing bone in spine | 2 | 2.1% |
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Difficulty with anesthesia | 26 | 27.1% |
|
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Positive family history | 5 | 5.2% |
Regarding the upper extremity, there were many reported differences. Thirty-five had abnormal, missing, or shortened fingers (36.46%). Seventeen had syndactyly (17.71%). Sixteen had stiffness in the arm or shoulder (16.67%). Twenty-eight had nerve deficits in the arms (29.27%). Three had other diagnoses relevant to the upper extremity that were not asked about in the survey (3.125%).
Nearly half of individuals reported a difference in the lower extremity. Twenty-nine reported stiffness in the lower extremity (30.28%). Seventeen had abnormal toes (17.71%). Six had fused toes (6.250%). Forty had been diagnosed with clubfoot (41.67%). Three had been diagnosed with congenital vertical talus (3.125%). Thirty-seven have flat feet (38.54%). Twenty-three had nerve deficits in the legs (23.96%). Nine of the ninety-six had other diagnoses relevant to the lower extremity that were not addressed (9.375%). Seven patients specifically mentioned problems with weak or underdeveloped calves in their responses. Deformity may be severe and not necessarily symmetric. Despite modern treatment methods that have had increased success rates relative to historical primary surgical treatment, many individuals required surgical care and revision surgical procedures for clubfoot in our series.
Twenty-nine of the ninety-six patients had been diagnosed with missing or weak chest muscles (30.21%). Fourteen had been diagnosed with missing or weak back muscles (14.58%). Twenty-three had an atypical contour of the sternum, a sunken chest, pigeon chest, or asymmetry (23.96%). Twenty-five had a shoulder or scapula abnormality (26.04%). Eight had a diagnosis of the trunk other than those addressed (8.333%).
Twenty-seven of the ninety-six respondents had a diagnosis of scoliosis (28.13%). Ten had a diagnosis of kyphosis (10.42%). Five had a diagnosis of lordosis (5.208%). Two had a diagnosis of missing or malformed bones in the spine (2.083%). None of the patients said they had a diagnosis of fused bones in the spine. Four had spinal abnormalities that were not addressed in the survey (4.167%).
Eighty-five of ninety-six patients cannot move their eyes side to side (88.54%). Ninety are not able to smile/raise their eyebrows (93.75%). Seventy-four had a small jaw bone (77.08%). Thirteen of the ninety-six patients had been diagnosed with a cleft palate (13.54%), and seventeen had a high palate (17.71%). Thirty-nine had facial deformities that were not addressed in the survey (40.63%).
Twenty-five of the ninety-six were identified as having problems with anesthesia (26.04%). Unfortunately, we were unable to detail the specifics of trouble with anesthesia in this series. Future research efforts will be focused in this area.
Ninety-four of the patients responded to questions about family members with Mobius Syndrome. Five of them reported family members with Mobius Syndrome (5.319%). Another five were unsure about Mobius Syndrome in the family because of issues with adoption.
Mobius Syndrome is a rare congenital disorder with a significant risk of associated orthopedic pathology. While the etiology of Mobius Syndrome has yet to be definitively elucidated, numerous promising theories have been reported which may explain the high association with orthopedic pathology [
A retrospective review in the plastic surgery literature including 27 patients reported 5 patients with scoliosis (18.52%) and 10 patients with lower limb deformity including clubfoot (2, 7.407%), flatfoot (1, 3.704%), metatarsus adductus (1), valgus (2), peroneal nerve deficiency (1), and congenital amputation (2). Three patients had syndactyly of the toes [
Due to our study design, we are unable to confirm the patients reported pathology with physical exam in all cases; however, the findings of the series of patients were similar to the overall survey with a slightly higher percentage of clubfoot and a slightly lower percentage of upper extremity syndactyly and scoliosis in the patient series. Our study’s greatest strength is the high number of responses recorded and analyzed. This was backed up with a series of 23 patients demonstrating similar incidence. Mobius Syndrome appears to have a remarkably high association with musculoskeletal pathologies, many of which require treatment at an early age for optimal outcomes (clubfoot, hip dysplasia).
Parents of children with Mobius Syndrome and bilateral clubfoot should be counseled that their child’s clubfoot may be more likely to require surgical or revision surgical care than idiopathic clubfoot. Unilateral deformity appears to be less severe and more responsive to standard treatment.
Perhaps our most important conclusion from a surgical standpoint is the high incidence of perceived anesthetic complications on the part of our cohort. As surgeons strive to first “do no harm,” we should have our patients with Mobius Syndrome carefully evaluated for anticipated airway difficulty and anesthetized by only those with significant experience with challenging airways and potential anesthetic complications.
In summary, this series of patients with Mobius Syndrome represents the largest series of patients to date establishing the incidence of orthopedic manifestations in the syndrome. It is our hope that this information will be helpful for those physicians who encounter this rare disease, in terms of identifying and providing timely treatment for associated conditions and for assisting in counseling patients and their families regarding treatment of their condition.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Both the survey study and the case series were conducted under the oversight of the Institutional Review Board at Brown University and Rhode Island Hospital.
Informed consent was obtained from all individual participants included in the study.
Level of evidence is IV (case series).
All authors declare that they have no financial or other relevant conflict of interests regarding this paper.
The authors wish to thank Dr. Kathryn Kraus for her expertise in photography and dedication to patients affected by Mobius Syndrome.