The patients we describe shed light on VACTERL association outside of the pediatric period. In our experience, patients and families with features of VACTERL association are told very little about long-term prognoses and outcomes, perhaps due to a dearth of published information. Because of this, we feel that a descriptive case series such as is presented here can be a valuable resource for both medical caregivers and for affected patients and families.
Overall, the patients reported here demonstrate two central points. First, medically significant malformations that are component features of VACTERL association, especially those affecting the vertebrae, heart, and kidneys, may not be ascertained until adulthood. Strikingly, almost one-quarter of malformations that are core component features of VACTERL association were not identified until after childhood, and in over half of patients, the diagnosis of VACTERL association was not made until adulthood, though this may very well be due to the fact that the condition now termed VACTERL association was first described after many patients described here were born. Currently, greater awareness of VACTERL association and similar conditions may result in improved ascertainment of malformations. Some anomalies, such as TEF or imperforate anus, are usually obvious in the neonatal period, but in many of our patients, other malformations were only noted later in life as an incidental finding, as in one case when an X-ray was performed after a coincidental traumatic injury. In our cohort, these late-diagnosed malformations resulted in medically significant issues later in life, such as debilitating back pain related to vertebral anomalies, or unilateral renal agenesis with a dysplastic remaining kidney or the presence of a cardiac malformation necessitating careful follow-up of renal or cardiac function. It is thus important for medical professionals such as practitioners of general/family medicine, internal medicine, and other specialists who regularly see adult patients to be aware of conditions like VACTERL association that have traditionally been the purview of pediatricians and pediatric subspecialists.
Second, the experiences of adult patients with features of VACTERL association indicate that in many patients, medical sequelae of the primary malformations persist or are first reported in adulthood. The majority of patients with vertebral malformations continued to experience back, shoulder, and/or neck pain, which was particularly severe in two patients. The typical age of onset of back pain in our cohort was lower than that in the general population [10
], and though our cohort is small, the severity of the initial vertebral malformations did not appear qualitatively greater in patients with severe back pain. In view of these observations, we recommend that all patients with vertebral anomalies continue to have this issue carefully followed in adulthood, with a low threshold for referral for further management.
In terms of anal anomalies, it is well established that sequelae of imperforate anus/anal atresia can be debilitating [20
]. Several patients report complications such as severe constipation and intestinal blockage requiring hospitalizations. Functional stooling problems and poor quality of life persisted in many children treated for anorectal malformations, and quality of life may worsen with age [13
]. Attention to these issues in adults with VACTERL association, as well as up-to-date knowledge of the continuously emerging surgical options for incontinence [5
] and non-surgical options such as biofeedback therapy [42
], may be helpful.
While a spectrum of renal issues exists in many patients – and admittedly, some patients have renal issues but no identified structural renal anomaly – the most commonly observed medical problems are nephrolithiasis and UTIs (in both genders). This may be explained by findings in a small previous study, in which 43% of pediatric patients with genitourinary involvement had severe urinary tract reflux, which can cause kidneys stones and UTIs [37
]. Although our group only included one patient with impaired renal function, many patients with VACTERL association survive into adulthood with renal anomalies that can cause chronic kidney disease and associated morbidities [1
In patients with repaired TEF, problems such as dysphagia, choking, and gastroesophageal reflux can be attributed to poor esophageal motility, while respiratory issues may include reactive airway disease and tracheomalacia. These issues may relate to sequelae of the TEF itself, to surgical repair of the TEF, or to underlying cellular differences. The presence of these issues is unsurprising: in several analyses of morbidity and mortality associated with TEF/EA, many patients have been documented with recurrent respiratory infections, dyspnea, dysphagia, gastroesophageal reflux, tracheomalacia, and an increased risk of esophageal malignancy [9
]. The presence of formally diagnosed asthma in patients with repaired TEF is less well established: while wheezing and other respiratory symptoms are often documented, it is not always clear whether patients meet criteria for the diagnosis of asthma or if the symptoms are attributable to effects of the TEF [19
]. Several quality of life studies show that most survivors of TEF/EA repair enjoy a normal quality of life [12
Despite these conclusions, major limiting factors of this study include its retrospective nature, which may create an undue emphasis on more severe cases, and lack of uniform examination, both in contrast to the cohort followed by Wheeler and Weaver approximately 20 years after initial ascertainment [40
]. In addition, in the absence of uniformly applied diagnostic criteria, it is difficult to ascertain how accurately the patients in our cohort and those in Wheeler and Weaver’s cohort represent the entire population of affected patients. In agreement with the conclusions of Wheeler and Weaver, our patients have normal intelligence and can live independently. Our findings echo common themes regarding complications of anal and genital anomalies that could lead to infertility. Unlike Wheeler and Weaver’s study, our analysis highlights other sequelae, such as those relating to vertebral malformations (e.g., back pain), TEF (e.g. gastroesopheal reflux and reactive airway disease), and renal anomalies (e.g. nephrolithiasis and UTIs). The patients in our cohort were not smaller in size than average. Interestingly, as in the previous study, hearing loss was reported in several patients in our cohort, though explanations (e.g., neonatal medication toxicity, working in environments with loud noises) did not necessarily suggest a pathogenic process related to VACTERL association or overlapping disorders among our patients.
We hope that improved care will result from anticipation of the issues described here. Because VACTERL association may be less familiar to adult practitioners, it is important for older patients to continue seeing caregivers who are knowledgeable about the condition. Additionally, as medically significant findings in patients with VACTERL association may be missed unless a comprehensive clinical work-up is performed, we suggest that patients in whom a diagnosis of VACTERL association is considered undergo testing and/or examination for the presence of each of the core component features, with the following initial testing at a minimum: a thorough history and physical examination by a clinician familiar with the condition, X-rays of the entire spine with consideration of spinal MRI and/or ultrasound, echocardiogram, and renal ultrasound with blood and urine testing for renal function. As previous studies have suggested, and which is echoed in the patients described here, clinicians should also be aware that component features of VACTERL association are more common in relatives of patients than in the general population; thus, a careful family history with further work-up as medically indicated is advised in family members of affected patients [32
]. Finally, as patients age, clinicians should continue to maintain a low threshold for considering and working up the common medical issues described in our cohort.