Clinical/Case Report

The Cleft Palate Craniofacial Journal

1‐6
Failure of Mandibular Distraction Osteogenesis © 2023, American Cleft Palate
Craniofacial Association
in Klippel- Feil Syndrome- 4: A Case Report of a Article reuse guidelines:
Rare Syndromic Robin Sequence sagepub.com/journals-permissions
DOI: 10.1177/10556656231220852
journals.sagepub.com/home/cpc

Emma Yanko, BSc1 , Brandon Spink, BSc1, and Craig Gendron, MD2

Abstract
Klippel-Feil syndrome-4 (KFS4), a rare autosomal recessive form of Klippel- Feil syndrome, is characterized by facial dysmor-
phism, nemaline myopathy, and short stature. Only 10 cases of KFS4 have been previously published in the literature. We report
a novel case of a 1- month-old girl with known KFS4 and Robin Sequence (RS). At 2 months old, she underwent bilateral man-
dibular distraction osteogenesis to correct significant airway obstruction. Despite adequate mandibular advancement, the patient
failed extubation twice and eventually required a tracheostomy. Due to the multiple anomalies present in KFS4, mandibular dis-
traction osteogenesis may have a decreased likelihood of surgical success.

Keywords
craniofacial morphology, mandible, outcomes, Pierre Robin sequence, upper airway obstruction

Introduction We report a novel case of a 1-month-old girl with KFS4 and

Robin sequence (RS), previously known as Pierre Robin
Sequence, is a rare congenital condition first described in
1923 by French dentist, Pierre Robin.1 It is characterized by
micrognathia, glossoptosis, and upper airway obstruction.
Cleft palate, while not considered a mandatory characteristic
of the condition, is present in up to 90% of patients with
RS.2 RS can occur in isolation, however, 50% of patients
have an associated syndromic condition or chromosomal
abnormality.3 To date, more than 50 different syndromes
have been associated with RS.4
Klippel-Feil syndrome (KFS), first reported in 1912 by Maurice
Klippel and Andre Feil, is a rare multisystem disease characterized
by the congenital fusion of two or more vertebrae in the cervical
spine.5 These patients typically present with a triad of limited cer-
vical range of motion, an abnormally short neck, and a low poste-
rior hairline.6 Other spinal and extraspinal anomalies have been
reported in patients with KFS, including Sprengel deformity, con-
genital scoliosis, and several visceral pathologies.6,7 Klippel-Feil
syndrome-4 (KFS4; OMIM#616549) is an autosomal recessive
form of KFS caused by biallelic pathogenic variants in
MYO18B.8,9 KFS4 is a rare condition; to our knowledge, only
10 cases have been reported in the literature.8,9 Unlike KFS,
these patients often present with nemaline myopathy, facial dys-
morphism, and short stature.8 Although micrognathia has been
reported as a craniofacial phenotype in patients with KFS4, man-
dibular distraction osteogenesis for concurrent RS has not been
described to our knowledge.10
RS who underwent bilateral mandibular distraction osteogene-
sis (MDO) with internal Micro Zurich distraction devices (KLS
Martin) for correction of RS.
Case Report
A 1-month-old girl with previously diagnosed KFS4 and RS
was admitted to the hospital with upper airway obstruction
and failure to thrive.
Previously, at two weeks of age, the patient underwent
whole exome sequencing due to a constellation of anomalies,
including facial dysmorphism with severe micrognathia, retro-
gnathia, and glossoptosis. Other findings included nemaline
myopathy causing hypotonia of the upper extremities, and
severe scoliosis (Table 1). The genetic testing results showed
that the patient is a compound heterozygote for two variants
in the MYO18B gene, leading to the diagnosis of Klippel-Feil
syndrome-4 (KFS4).
Regarding her upper airway obstruction, the patient was
evaluated by a multidisciplinary team. This included pediatric
1
College of Medicine, University of Saskatchewan, Canada
2
Department of Surgery, Division of Plastic Surgery, College of Medicine,
University of Saskatchewan, Canada
Corresponding Author:
Emma Yanko, 107 Wiggins Rd, Saskatoon, SK S7N 5E5, Canada.
Email: yanko.emma@usask.ca
2 The Cleft Palate Craniofacial Journal 0(0)
plastic surgery, otolaryngology, anesthesia, and respirology. A
full night unobserved smart monitor study on 0.2 L/ minute of
low-flow oxygen was completed, and the patient was classified
with moderate obstructive apneas. Nasal laryngoscopy demon-
strated glossoptosis and a normal-looking larynx and vocal
cords. Flexible scope demonstrated mild, distal tracheomala-
cia, no concerning tracheal stenosis, and some pulsatility
along the right mainstem bronchus, potentially due to an aber-
rant subclavian artery in the area.
Table 1. Known Anomalies in Case Report Patient Diagnosed with
Klippel-Feil Syndrome-4 and Robin Sequence.
System or Anatomic
Area Findings
Craniofacial • Glossoptosis
• Micrognathia
• Retrognathia
• U-shaped cleft palate
• Microcephaly
Musculoskeletal • Scoliosis at the level of thoracolumbar
vertebrae
• Thoracic spine fusion
• Bilateral hip subluxation
• Club feet
• Nemaline myopathy, with hypotonia of the
upper extremities
• Arthrogryposis of the hands
Respiratory • Tracheomalacia
• Mild restrictive lung disease secondary to
scoliosis
Cardiovascular • Small atrial septal defect
• Potential aberrant subclavian artery
Figure 1. Computed tomography image reconstruction: lateral (A), anterior (B) demonstrating severe micro-/retrognathia.
A computed tomography (CT) head showed severe micro-
gnathia and retrognathia, with a large anterior-posterior (AP)
discrepancy between the maxillary and mandibular dentition,
as well as glossoptosis (Figures 1 and 2). These findings
were concluded to be the primary cause of the patient’s
severe upper airway obstruction; given this, the patient was
determined to be a candidate for mandibular distraction
osteogenesis.
At baseline, the patient had upper airway obstruction on
clinical examination and required high-flow nasal cannulation.
Nasogastric (NG) tube feeding, which the patient had been on
since postnatal discharge from the neonatal intensive care unit
(NICU), was continued to prevent further aspiration and
promote weight gain. Antibiotics were initiated for suspected
aspiration pneumonitis.
After a discussion of the risk and benefits of MDO, the
patient’s parents opted to proceed with surgery in hopes of
avoiding tracheostomy despite the increased chance of surgical
failure. At two months and four days of age, the patient under-
went bilateral mandibular distraction with the placement of
internal Micro Zurich distraction devices (KLS Martin) as
well as gastrostomy tube placement (Figures 3 and 4).
Regarding the surgical techniques used, bilateral Risdon inci-
sions were made 1.5 cm below the mandibular border.
Subperiosteal dissection of the mandible was carried out,
revealing the angle of the mandible as well as the area to
place the distractor. The Sonopet(®) ultrasonic bone aspirator
(Stryker(®), Kalamazoo, MI) was then used to cut the bone
and make a corticotomy in the lateral and inferior surface of
the bone. After securing the distractors bilaterally, the bone
was fractured by distracting the devices approximately
2-3 mm, using a 2 mm osteotome, and completing posterior
corticotomy. The distractors were then backed off to the start-
ing position.
Yanko et al
Post-operatively, the patient remained intubated and was
sent to the NICU for post-operative healing and mandibular
advancement. Starting on postoperative day one, the distractors
were turned daily for 15.5 days (distraction rate of 1.2 mm/
day). Leading to a total of 18.6 mm of distraction. Before hard-
ware removal, twenty weeks were allowed for consolidation.
After completion of MDO, there appeared to be mild retrogna-
thia and the glossoptosis was corrected.
However, despite adequate mandibular advancement, the
patient failed two extubation attempts due to ongoing upper
airway obstruction. To minimize the complication risk associ-
ated with prolonged intubation, a tracheostomy was performed
Figure 2. Computed tomography: sagittal view demonstrating
severe micro-/retrognathia.
Figure 3. Pre- mandibular distraction osteogenesis photographs (A and B) demonstrating severe micro-/retrognathia.
3
to secure the airway at four weeks post-MDO surgery.
Mandibular distraction hardware removal occurred when the
patient was six months old, and twenty weeks post MDO
surgery (Figure 5).
At the time of writing, the patient is now 30 months old and
continues to have a tracheostomy tube. She requires continued
tracheostomy management for respiratory secretions.
Discussion
Robin sequence is a craniofacial anomaly characterized by a
collection of findings; these include micrognathia, glossopto-
sis, and, commonly cleft palate, which results in upper
airway obstruction and feeding difficulties.3,4,11 RS may
occur in isolation (iRS) or as a feature of other congenital
Figure 4. Placement of internal Micro Zurich distraction devices
(KLS Martin).
4 The Cleft Palate Craniofacial Journal 0(0)
Figure 5. Post mandibular distraction osteogenesis hardware removal photograph demonstrating clinically improved micro-/retrognathia
(A and B).
syndromes, termed syndromic Robin Sequence (sRS). Patients
with additional anomalies and/or chromosomal defects without
an identified syndrome are classified into the Robin Sequence
plus group (RS-plus). The clinical expression of RS is hetero-
geneous with the severity of clinical obstruction presenting on
a spectrum.11–13 A patient with RS may be otherwise asymp-
tomatic or demonstrate some degree of upper airway obstruc-
tion ranging from mild respiratory distress to overt
obstruction requiring immediate intervention.
The management of RS is contingent on the severity of
upper airway obstruction as well as other presenting comorbid-
ities.11,12 There have been multiple algorithms developed to
aid in treatment decision-making for patients with RS,
though no formal consensus has been reached.11,13–15 The
majority of patients with RS see spontaneous improvement
or resolution of syndrome sequelae within the first two years
of life as both the mandible and upper airway increase in
size.16,17 Concurrent feeding difficulties and aspiration risk
can often be managed effectively with upright feeding tech-
niques, modification of the nipple for bottle feeding, or tempo-
rary tube feeding.11 Conservative airway management is also
reasonable in these patients and includes close observation
and prone positioning. In addition, the use of an orthodontic
airway plate, such as the pre-epiglottic baton plate (PEBP), is
a valuable treatment method that may be used in an attempt
to avoid more invasive treatment.18,19 Evidence suggests that
an orthodontic airway plate may offer similar airway-related
and feeding-related improvements in patients with RS when
compared to MDO.18
When conservative management is unsuccessful or the
patient is severely symptomatic, which often is the case with
syndromic RS, surgical intervention is indicated. Options for
surgical management include tongue-lip adhesion, mandibular
distraction osteogenesis, and tracheostomy.11,12,20 Mandibular
distraction osteogenesis in the treatment of symptomatic
micrognathia was first described in 1992 by McCarthy
et al.21 MDO has become a mainstay in the initial treatment
of patients with RS associated with severe airway obstruction,
obstructive sleep apnea, or oral feeding difficulties and has a
success rate of avoiding tracheostomy ranging from 84-
100%.11,13,22–27 Mandibular distraction osteogenesis is also
considered an effective method to facilitate decannulation in
patients with RS who underwent tracheostomy initially.3,11
The procedure works by lengthening the mandible in a
forward direction, consequently pulling the tongue anteriorly
through its muscular attachments on the lingual surface of
the mandible to increase the retrolingual airway.11 Multiple
techniques for MDO have been described, though oblique
osteotomies at the angle of the mandible remain the most
common approach and were used in this case.20 Compared
to alternative surgical options, MDO is a relatively safe proce-
dure with lower rates of long-term complications.3,11 In con-
trast, tracheostomy offers a definitive treatment for upper
airway obstruction but has associated risks of accidental decan-
nulation or mucous plugging.3 There is also potential long-
term morbidity related to peristomal scarring and tracheal
erosion in addition to the need for long-term maintenance
and home care.3
The patient presented in this case has Klippel-Feil
syndrome-4, an exceedingly rare disorder associated with mul-
tiple anomalies (Table 1). Although KFS4 is associated with
facial dysmorphism, micrognathia has only been described in
3 of the 10 known KFS4 cases reported in the literature.8,9
Due to the severity of this patient’s airway obstruction symp-
toms, surgical management was necessary in this case.
Unfortunately, although an adequate mandibular advancement
of 18.6 mm was achieved, the patient failed extubation twice
due to ongoing airway obstruction, resulting in the need for
a tracheostomy. As cited earlier, MDO is often successful in
correcting upper airway obstruction in RS sequence.
However, many of these studies only included a small percent-
age of patients with sRS. It has been suggested that patients with
sRS have poorer outcomes from MDO than those with iRS.11 The
comorbidities leading to the decreased surgical success of MDO
in RS treatment have not been well described. It has been reported
that in patients with multiple levels of airway obstruction, such as
Yanko et al
laryngomalacia, and tracheomalacia, MDO may not successfully
relieve the obstruction.14 In this patient’s case, ongoing airway
obstruction after MDO may have been due to one or more of
the following factors: severe scoliosis, mild tracheomalacia, and
nemaline myopathy. Given the numerous anomalies associated
with syndromic RS and RS-plus, we would be remiss if we did
not mention the necessity of early involvement of a multidisci-
plinary team in the assessment and management of this condi-
tion.28 As one example, specialists in pediatric respirology and
neurology are important in evaluating cardiopulmonary and neu-
rocognitive function to determine whether airway compromise is
the result of multilevel obstruction or central apnea.29
The decision to proceed with MDO in this patient, despite
an increased chance of failure, was due to multiple factors.
Firstly, the patient had a classic presentation of RS and
upper airway obstruction secondary to this. Although this
patient did have mild tracheomalacia and mild restrictive
lung disease secondary to severe scoliosis, these factors were
not thought to be the main cause of the patient’s airway
obstruction. In addition, the patient’s parents were aware that
given her comorbidities, there would be an increased likeli-
hood that she would require a tracheostomy after MDO.
However, the patient’s parents opted to proceed with the
initial MDO despite the increased risk of surgical failure.
Although the patient ultimately required a tracheostomy, the
patient’s parents are pleased with the improved anatomic
appearance, report increased ease of tracheotomy care given
the improved micro/retrognathia, and are relieved that the
medical team made every effort for their child before resorting
to tracheostomy.
Conclusion
Mandibular distraction osteogenesis is often successful in
treating patients with Robin Sequence who have failed conser-
vative therapy. However, co-morbidities in syndromic Robin
sequence may affect the surgical success of MDO. In the
context of Klippel-Feil syndrome-4, these co-morbidities
include concurrent airway, respiratory and musculoskeletal
anomalies. Presently, there is a lack of comprehensive under-
standing regarding the impact of co-morbidities on the effec-
tiveness of mandibular distraction osteogenesis. Further
research is needed to clarify this matter. It is essential to con-
sider specific patient and family factors coupled with a multi-
disciplinary assessment of the patient to evaluate the
potential risks and advantages associated with mandibular dis-
traction osteogenesis in these individuals.
Consent
Written, informed consent was obtained by the patient’s parents for
the collection of patient information and photographs to be published
in this case report.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to
the research, authorship, and/or publication of this article.
5
Funding
The authors received no financial support for the research, authorship,
and/or publication of this article.
ORCID iD
Emma Yanko https://orcid.org/0000-0001-8655-4642
References
1. Robin P. La chute de la base de la langue consideree comme une
nouvelle cause de gene dans la respiration naso-pharyngienne.
Bull Acad Med Paris. 1923;89:37-41.
2. Breugem CC, Evans KN, Poets CF, et al. Best practices for
the diagnosis and evaluation of infants with Robin sequence: A
clinical consensus report. JAMA Pediatr. 2016;170(9):894-902.
doi:10.1001/jamapediatrics.2016.0796
3. Zaballa K, Singh J, Waters K. The management of upper airway
obstruction in Pierre Robin sequence. Paediatr Respir Rev.
Published online July 2022:S1526054222000471. doi:10.1016/
j.prrv.2022.07.001
4. Tan TY, Kilpatrick N, Farlie PG. Developmental and genetic per-
spectives on Pierre Robin sequence. Am J Med Genet C Semin
Med Genet. 2013;163(4):295-305. doi:10.1002/ajmg.c.31374
5. Menger RP, Rayi A, Notarianni C. Klippel Feil syndrome. In:
StatPearls. StatPearls Publishing; 2022. Accessed October 9,
2022. http://www.ncbi.nlm.nih.gov/books/NBK493157/
6. Litrenta J, Bi AS, Dryer JW. Klippel-Feil syndrome: Pathogenesis,
diagnosis, and management. J Am Acad Orthop Surg. 2021;29(22):
951-960. doi:10.5435/JAAOS-D-21-00190
7. Jae-Min Park A, Nelson SE, Mesfin A. Klippel-Feil syndrome:
Clinical presentation and management. JBJS Rev. 2022;10(2).
doi:10.2106/JBJS.RVW.21.00166
8. Altuame FD, Haldeman-Englert C, Cupler E, et al. Further delin-
eation of MYO18B-related autosomal recessive Klippel-Feil syn-
drome with myopathy and facial dysmorphism. Am J Med Genet
A. 2021;185(2):370-376. doi:10.1002/ajmg.a.61957
9. Brunet T, Westphal DS, Weber S, et al. A novel pathogenic
variant in MYO18B associating early-onset muscular hypotonia,
and characteristic dysmorphic features, delineation of the
phenotypic spectrum of MYO18B-related conditions. Gene.
2020;742:144542. doi:10.1016/j.gene.2020.144542
10. Alazami AM, Kentab AY, Faqeih E, et al. A novel syndrome of
Klippel-Feil anomaly, myopathy, and characteristic facies is
linked to a null mutation in MYO18B. J Med Genet.
2015;52(6):400-404. doi:10.1136/jmedgenet-2014-102964
11. Lam DJ, Tabangin ME, Shikary TA, et al. Outcomes of mandib-
ular distraction osteogenesis in the treatment of severe microgna-
thia. JAMA Otolaryngol Neck Surg. 2014;140(4):338-345.
doi:10.1001/jamaoto.2014.16
12. Sher AE, Shprintzen RJ, Thorpy MJ. Endoscopic observations
of obstructive sleep apnea in children with anomalous
upper airways: Predictive and therapeutic value. Int J Pediatr
Otorhinolaryngol. 1986;11(2):135-146. doi:10.1016/S0165-
5876(86)80008-8
13. Correia-Sá I, Horta R, Neto T, Amarante J, Marques M. Lehman
syndrome: A new syndrome for Pierre Robin sequence. Cleft
Palate Craniofac J. 2015;52(3):369-372. doi:10.1597/13-063
14. Li WY, Poon A, Courtemanche D, et al. Airway management in
Pierre Robin sequence: The Vancouver classification. Plast Surg.
2017;25(1):14. doi:10.1177/2292550317693814
6 The Cleft Palate Craniofacial Journal 0(0)
15. Schaefer RB, Stadler JA, Gosain AK. To distract or not to dis-
tract: An algorithm for airway management in isolated Pierre
Robin sequence. Plast Reconstr Surg. 2004;113(4):1113-1125.
doi:10.1097/01.PRS.0000110323.50084.21
16. Hicks KE, Billings KR, Purnell CA, et al. Algorithm for airway
management in patients with Pierre Robin sequence. J
Craniofac Surg. 2018;29(5):1187-1192. doi:10.1097/SCS.
0000000000004489
17. Katz ES, Mitchell RB, D’Ambrosio CM. Obstructive sleep apnea
in infants. Am J Respir Crit Care Med. 2012;185(8):805-816.
doi:10.1164/rccm.201108-1455CI
18. Abbas DB, Lavin C, Fahy EJ, et al. A systematic review of man-
dibular distraction osteogenesis versus orthodontic airway plate
for airway obstruction treatment in Pierre Robin sequence. Cleft
Palate Craniofac J. 2022;59(3):365-376. doi:10.1177/10556656
211011886
19. Bütow KW, Naidoo S, Zwahlen RA, Morkel JA. Pierre Robin
sequence: Subdivision, data, theories, and treatment - part 4:
Recommended management and treatment of Pierre Robin
sequence and its application. Ann Maxillofac Surg. 2016;
6(1):44-49. doi:10.4103/2231-0746.186136
20. Luana N, Marco Z, Francesca DB, et al. Age and upper airway
obstruction: A challenge to the clinical approach in pediatric
patients. Int J Environ Res Public Health. 2020;17(10):3531.
doi:10.3390/ijerph17103531
21. McCarthy JG, Schreiber J, Karp N, Thorne CH, Grayson BH.
Lengthening the human mandible by gradual distraction. Plast
Reconstr Surg. 1992;89(1):1-8. discussion 9-10.
22. Tibesar RJ, Sidman JD. Mandibular distraction osteogenesis in
the pediatric patient. Curr Opin Otolaryngol Head Neck Surg.
2008;16(6):548-554. doi:10.1097/MOO.0b013e3283177f81
23. Tibesar RJ, Scott AR, McNamara C, Sampson D, Lander TA,
Sidman JD. Distraction osteogenesis of the mandible for airway
obstruction in children: Long-term results. Otolaryngol–Head
Neck Surg Off J Am Acad Otolaryngol-Head Neck Surg.
2010;143(1):90-96. doi:10.1016/j.otohns.2010.02.018
24. Miloro M. Mandibular distraction osteogenesis for pediatric
airway management. J Oral Maxillofac Surg Off J Am Assoc
Oral Maxillofac Surg. 2010;68(7):1512-1523. doi:10.1016/j.
joms.2009.09.099
25. Lidsky ME, Lander TA, Sidman JD. Resolving feeding diffi-
culties with early airway intervention in Pierre Robin
sequence. Laryngoscope. 2008;118(1):120-123. doi:10.1097/
MLG.0b013e31815667f3
26. Denny A, Amm C. New technique for airway correction in
neonates with severe Pierre Robin sequence. J Pediatr. 2005;
147(1):97-101. doi:10.1016/j.jpeds.2005.02.018
27. Dauria D, Marsh JL. Mandibular distraction osteogenesis for
Pierre Robin sequence: What percentage of neonates need it? J
Craniofac Surg. 2008;19(5):1237-1243. doi:10.1097/SCS.
0b013e3181843293
28. Bull MJ, Givan DC, Sadove AM, Bixler D, Hearn D. Improved
outcome in Pierre Robin sequence. Effect of Multidisciplinary
Evaluation and Management. Pediatrics. 1990;86(2):294-301.
doi:10.1542/peds.86.2.294
29. Khayat A, Bin-Hassan S, Al-Saleh S. Polysomnographic findings
in infants with Pierre Robin sequence. Ann Thorac Med.
2017;12(1):25-29. doi:10.4103/1817-1737.197770