Klippel Feil Syndrome: Clinical Phenotypes Associated With Surgical Treatment

Laureen D. Hachem, MD; Francois Mathieu, MD; Maria Lamberti-Pasculli, RN; Brian W. Hanak, MD; Reinhard Zeller, MD; Abhaya V. Kulkarni, MD, PhD; James Drake, MD, MS; George M. Ibrahim, MD, PhD

Disclosures

Spine. 2020;45(11):718-726. 

In This Article

Abstract and Introduction

Abstract

Study Design: Retrospective study.

Objective: To define distinct Klippel-Feil syndrome (KFS) patient phenotypes that are associated with the need for surgical intervention.

Summary of Background Data: KFS is characterized by the congenital fusion of cervical vertebrae; however, patients often present with a variety of other spinal and extraspinal anomalies suggesting this syndrome encompasses a heterogeneous patient population. Moreover, it remains unclear how the abnormalities seen in KFS correlate to neurological outcomes and the need for surgical intervention.

Methods: Principal component (PC) analysis was performed on 132 KFS patients treated at a large pediatric hospital between 1981 and 2018. Thirty-five variables pertaining to patient/disease-related factors were examined. Significant PCs were included as independent variables in multivariable logistic regression models designed to test associations with three primary outcomes: cervical spine surgery, thoracolumbar/sacral spine surgery, and cranial surgery.

Results: Fourteen significant PCs accounting for 70% of the variance were identified. Five components, representing four distinct phenotypes, were significantly associated with surgical intervention. The first group consisted of predominantly subaxial cervical spine fusions, thoracic spine abnormalities and was associated with thoracolumbar/sacral spine surgery. The second group was largely represented by axial cervical spine anomalies and had high association with cervical subluxation and cervical spine surgery. A third group, heavily represented by Chiari malformation, was associated with cranial surgery. Lastly, a fourth group was defined by thoracic vertebral anomalies and associations with sacral agenesis and scoliosis. This phenotype was associated with thoracolumbar/sacral spine surgery.

Conclusion: This is the first data-driven analysis designed to relate KFS patient phenotypes to surgical intervention and provides important insight that may inform targeted follow-up regimens and surgical decision-making.

Level of Evidence: 3

Introduction

Klippel-Feil syndrome (KFS) is a rare condition characterized by the congenital fusion of 2 or more cervical vertebrae. The incidence of KFS is estimated to be one in 40,000 with a prevalence close to 0.7%.[1,2] The clinical triad of a short neck, low posterior hairline, and limited neck range of motion first described by Klippel and Feil in 1912[3] was originally thought to be the hallmark presentation of this condition. However, this triad is present in <50% of KFS patients. Moreover, numerous other spinal and extraspinal anomalies have been reported in patients with KFS suggesting that this syndrome likely encompasses a heterogeneous patient population.[4,5]

Various classification systems have been proposed for KFS, many of which are based on patterns of fusion anomalies within the cervical spine.[3,6,7] However, these classifications have failed to incorporate the range of other abnormalities present in patients with KFS and have yet to show strong associations with clinical outcomes. Vertebral segmentation anomalies or formation defects, depending on location, may predispose to hypermobility and eventual instability. Moreover, specific patterns of anomalies may precipitate aberrant alignment and deformities necessitating surgery. To date, it remains unclear how the abnormalities seen in KFS correlate to neurological outcomes and the need for surgical intervention. It is likely that the natural history of KFS is dictated not only by the nature of vertebral fusions, but also the many other spinal and extra-spinal abnormalities. Determining specific patient phenotypes that may be associated with a higher risk of requiring a surgical intervention is essential in better understanding the natural history of KFS and guiding treatment paradigms.

To better characterize the heterogeneity across KFS patients, we studied patients treated over nearly four decades at our institution. We hypothesized that patients could be subdivided into distinct phenotypes based on patient and disease-related variables and that these phenotypes may have unique associations with the need for surgical intervention. Using principal component analysis (PCA), we identified four distinct phenotypes which were significantly associated with spinal or cranial surgery. This is the first data-driven algorithm designed to relate patient phenotypes to surgery intervention in KFS patients.

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