In the present study, data from patients with congenital insensitivity to pain who underwent guided growth procedures around the knee were reviewed. Our results suggest that in carefully selected CIP patients, correction of the knee deformity might be achieved with a low rate of complications. Our primary goal in offering elective surgery to CIP patients is the prevention of devastating complications (including knee subluxation and dislocation) and not cosmesis. None of our patients experienced worsening of the knee deformity or subluxation/dislocation. However, this study is limited by its design and rarity of the disease and cannot establish a causal relationship/
CIP is extremely rare, with the largest populations of patients being reported from Israel [15] and Japan [16]. The genotypic and phenotypic characteristics of patients are heterogeneous, and multiple genetic mutations and phenotypes are reported in the literature [6, 17,18,19]. Dyck’s classification is used by most clinicians, and although it might not include every possible disease manifestation, being based on phenotypic characteristics makes this classification relevant in the clinical setting. Type I (which has at least 6 subtypes) is the most genetically heterogeneous and is believed to be the most common form of CIP [20]. It is the only HSAN showing autosomal dominant inheritance pattern and is generally diagnosed in early adulthood [10]. Therefore, unless diagnosed early, these patients would not be candidates for guided growth procedures.
Type II is characterized by early-onset sensory deficit, anhidrosis, autonomic dysfunction including recalcitrant constipation, recurrent ulcers and paronychia of the fingers and toes, and apnea, in addition to self-mutilation [6]. Severe medical issues preclude any elective surgical procedure in these individuals, and we did not have any patients with HSAN type II in this series.
Type III, also called familial dysautonomia or Riley-Day syndrome, is most commonly diagnosed based on sympathetic autonomic dysfunction, which could manifest as nausea and vomiting, tachycardia, hypotonia, orthostatic hypotension, and decreased or absent lacrimation [6]. Intellectual disability, along with the increased risk of anesthesia-related complications, renders this group of patients poor surgical candidates. HSAN type III is essentially limited to children of Ashkenazi Jewish descent, and we have not diagnosed any at our institution [21].
Type IV, also known as congenital insensitivity to pain with anhidrosis (CIPA) is an autosomal recessive disorder, diagnosed in childhood, and is characterized by anhidrosis, varying degrees of intellectual disability, and loss of oral sensation, which leads to face and mouth mutilation (Fig. 3a) [6]. Three of our patients (five knees) were categorized in this group. Interestingly, all suffered from lip and tongue bites and loss of teeth, but with no finger or toe loss (Fig. 2), which suggests different mechanisms for these two seemingly similar manifestations. All three also had dystrophic nails.
Patients with HSAN type V generally have no intellectual disability, although joint deformities are common [22]. Three of our patients were in this group. All had normal facies (Fig. 1a) and intelligence.
While we did not select patients based on their phenotypic classification, we only had type IV and V patients in this study. However, other types of HSAN are generally not ideal candidates for guided growth, due to the typical age at diagnosis (type I) and severe intellectual disability and self-mutilating behavior (type II), and intellectual disability with comorbid neurologic dysfunction (type III). Additionally, nine deformities in this series were valgus, and only one case of tibia vara. While the literature is not conclusive, a valgus deformity is to be expected in CIP, as patients are typically diagnosed during the growth period where a physiologic genu valgum is present. The repeated microinjuries due to the lack of pain and proprioception concentrates the abnormal forces on the lateral hemijoint and leads to a progressive valgus deformity, instability and, if left untreated, dislocation.
There are no reports of elective surgeries performed to prevent secondary complications in patients with CIP, but the results of corrective procedures have generally not been promising. Specifically, hip subluxations and dislocations do poorly after reconstructive surgery [12]. We believe that just as patients with no underlying neuropathy tolerate hip dislocation for decades with minimal limitations, the ambulatory status of CIP patients is not dependent on reduced hip joints, and reconstructive hip surgeries should not be offered to these individuals. However, at least one report of total hip arthroplasty has been published, with no short-term complications [23].
The same, however, could not be said of knee deformities, which are progressive and can preclude walking without aid if not corrected. Successful knee fusion has been reported for a grossly unstable, arthritic, or dislocated knee [24]. However, in patients with multiple comorbidities or chronically infected joints, as well as wheelchair-dependent patients, amputation should also be considered and discussed with the patient, either as a primary procedure or in case of failure of the reconstructive procedures [8, 25,26,27]. Total knee arthroplasty has been performed in CIP patients and could be a viable option in a non-infected joint [28]. We have not yet performed any joint replacements in CIP patients. However, our purpose in performing guided growth procedures in CIP individuals is to mitigate the need for complex procedures with a high complication rate.
We achieved at least partial correction in all patients. The surgeries were timed to yield a full correction. However, a lower rate of correction was observed in all patients, when compared to patients with idiopathic genu valgum [14]. We observed a 0.28°/month correction rate in the femur, while previous studies have reported a rate of 0.4–0.52°/month [14]. Although anecdotal, we believe that patients with CIP grow at a lower rate, and guided growth procedures should be performed earlier than in non-CIP children.
We observed no major complications related to the surgeries during the study period. Staples had to be removed in one patient due to extrusion [29]. Tension-band plating was performed for four patients, with no hardware-related complications. We recommend using plates for guided growth in CIP patients. Also, none of the patients experienced skin dehiscence or surgical-site infection. We believe that the strict criteria with which we selected candidates for surgery might play a role in this low rate of complications [30]. We continue not to offer surgery to CIP patients with a severe intellectual disability or self-mutilating behavior. One of the patients died 4 years after surgery due to complications of a stabbing incident. Of note, this was the only patient with intellectual disability and behavioral issues in the series.
This study had several limitations. First, this is a small case series with only ten knees in six patients. No causal relationship could be inferred from such a study. However, due to CIP being an exceedingly rare disease, and surgical candidates even more so, this study is significant in introducing a preventive measure for this vulnerable patient population and reporting our clinical experience. Second, the indications for surgery were not standardized. Again, given the heterogeneity of clinical presentation, decisions should be made on a case-by-case basis, while following general guidelines. Third, although we performed surgeries to prevent the progression of knee deformity, we did not have a control group to compare the results with. Furthermore, long-term follow-up is needed to conclude the true success rate of guided growth procedures in CIP patients. It should also be noted that congenital insensitivity to pain (CIP) and hereditary sensory and motor neuropathy (HSAN) were used interchangeably in this paper. Although these terms are not necessarily equivalent, we chose CIP for the title, as orthopedic surgeons might be more familiar with the term, while neurologists might prefer HSAN.
To our knowledge, this is the first study to report the results of guided growth procedures in patients with congenital insensitivity to pain. Our findings suggest that guided growth procedures around the knee have a low complication rate in patients with CIP. The rate of correction was less than half of that predicted for idiopathic genu valgum. Based on our results, we recommend performing guided growth procedures in patients with no intellectual disability or self-mutilating behavior who have a cooperative family to adhere to strict activity limitations and regular follow-ups.