Parenting a child with Marfan syndrome: Distress and everyday problems

Abstract Marfan syndrome (MFS) is a multisystemic, autosomal dominant connective tissue disorder that occurs de novo in 25%. In many families, parent and child(ren) are affected, which may increase distress in parents. To assess distress, 42 mothers (29% MFS) and 25 fathers (60% MFS) of 43 affected children, completed the validated screening‐questionnaire Distress thermometer for parents of a chronically ill child, including questions on overall distress (score 0–10; ≥4 denoting “clinical distress”) and everyday problems (score 0–36). Data were compared to 1,134 control‐group‐parents of healthy children. Mothers reported significantly less overall distress (2, 1–4 vs. 3, 1–6; p = .049; r = −.07) and total everyday problems (3, 0–6 vs. 4, 1–8; p = .03; r = −.08) compared to control‐group‐mothers. Mothers without MFS reported significantly less overall distress compared to mothers with MFS, both of a child with MFS (1, 0–4 vs. 3.5, 2–5; p = .039; r = −.17). No significant differences were found between the father‐groups, nor between the group of healthy parents of an affected child living together with an affected partner compared to control‐group‐parents. No differences in percentages of clinical distress were reported between mothers and control‐group‐mothers (33 vs. 42%); fathers and control‐group‐fathers (28 vs. 32%); nor between the other groups. Distress was not associated with the children's MFS characteristics. Concluding, parents of a child with MFS did not show more clinical distress compared to parents of healthy children. However, clinical distress was reported in approximately one‐third and may increase in case of acute medical complications. We advise monitoring distress in parents of a child with MFS to provide targeted support.


| INTRODUCTION
Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by a pathogenic variant in FBN1 (Loeys et al., 2010) and occurs de novo in a quarter of patients. In many families, both a parent and one or more children are diagnosed with MFS. The estimated prevalence is 1:5,000-1:10,000 (Dietz, 1993) and the diagnosis is based on the revised Ghent criteria (Loeys et al., 2010). Children and adults/parents with MFS need regular medical follow-up (Hilhorst-Hofstee, 2013;Rozado, Martin, Pascual, Hernandez-Vaquero, & Moris, 2017;Tinkle & Saal, 2013) because of the risk of developing medical complications of the cardiovascular-(aortic aneurysm, mitral valve prolapse), musculoskeletal-and ophthalmic-(ectopia lentis, severe myopia) systems (Dietz, 1993;Faivre et al., 2012;Loeys et al., 2010;Sheikhzadeh et al., 2012;Stheneur et al., 2014;Velvin, Bathen, Rand-Hendriksen, & Geirdal, 2015a, 2016b. Therefore, parents may have extended caregiving responsibilities, both for their child/children with MFS and for themselves or their partner with MFS, which may further increase distress and everyday problems. In a recent study, we found that parents of a child with MFS reported parental burden caused by high parental caring requirements for their child's medical and psychosocial needs, lack of professional health care support, a limited social life, parental concerns about their child's physical, psychosocial development and fear of high-risk aortic surgery or early death . Also, in parents of children with other chronic illnesses, parental functioning was negatively affected (Pinquart, 2013) as well as their participation (Hatzmann, Peek, Heymans, Maurice-Stam, & Grootenhuis, 2014).
This study aims to assess distress and everyday problems of mothers and fathers without and with MFS, of a child with MFS using the DT-P. Data are compared to those of control-group mothers and fathers of a healthy child. Associations will be explored between distress in parents and the presence of MFS characteristics of the child.  (Haverman, van Oers, Limperg, Hijmans, et al., 2014;Haverman, van Rossum, van Veenendaal, van den Berg, et al., 2013

| Distress thermometer for parents (DT-P)
The DT-P is a validated screening instrument to identify overall distress, clinical distress and everyday problems in parents of a chronically ill child (Haverman, van Oers, Limperg, Houtzager, et al., 2013;van Oers et al., 2017). The DT-P consists of three parts. First, parents rate their overall distress in the past week on a "thermometer" ranging from 0 (no distress) to 10 (extreme distress) with a thermometer score ≥ 4 indicating clinically relevant distress (further referred to as "clinical distress"). Second, the occurrence of everyday problems is inquired by 36 or 34 problem item yes/no questions (for parents of a child <2 years or ≥ 2 years of age, respectively). There are six everyday problem domain scores: practical, social, emotional, physical, cognitive and parenting. These everyday problem domain scores are based on the number of times a "yes" is filled in for the everyday problem domain items. Third, additional questions inquire (a) perceived support from surroundings, (b) perceived lack of understanding from others concerning their situation, (c) parental chronic illness, (d) the wish to talk to a professional about their situation (yes, maybe or no) (Haverman, van Oers, Limperg, Houtzager, et al., 2013;van Oers et al., 2017). The internal consistency of the DT-P is acceptable with Cronbach's alphas ranging from 0.52 to 0.89 (van Oers et al., 2017).

| Marfan syndrome characteristics in children
The revised Ghent systemic score and the child-reported pain and fatigue were used to decribe the presence of MFS characteristics in children. Other characteristics that could have been used, for instance, aortic dilatation, lens luxation, foot-, lens-, pectus and/or scoliosis surgery, were too infrequently encountered. The revised Ghent systemic score is part of the revised Ghent criteria and is a method of assigning weighted values to the presence of clinical features that are associated with MFS. The score is calculated through the summation of applicable points (0-20). Experienced pain and fatigue of the child were discussed during the outpatient visit, 1 week after filling in the DT-P, and categorized in "no," "sometimes," or "often." Data were extracted from the child's medical file.

| Statistical analyses
Mothers and fathers of a child with MFS were analyzed as separate groups because of reported differences in distress levels (Conijn et al., 2019;Marchal et al., 2017;Schepers et al., 2018;Sultan et al., 2016; van The clinical distress score, everyday problem items and the additional questions were analyzed with Chi-square/Fisher's exact tests; odds ratios (OR) and confidence intervals (CI) were calculated. Following the previous DT-P studies, problem domain items were also analyzed for exploration and therefore, we did not correct for multiple testing. Correlation analyses (Spearman's rho) were used to explore associations between distress in parents and the presence of MFS characteristics of the child using the revised Ghent systemic score and the child-reported pain and/or fatigue.
Of the parents without MFS of a child with MFS, 14 mothers and 7 fathers lived together with an affected partner. No differences were found between the socio-demographic characteristics of mothers, fathers of a child with MFS and their children with MFS and control-group mothers, control-group fathers and their healthy children (Table 1), and between mothers without MFS and mothers with MFS, both of a child with MFS, nor between fathers without MFS and fathers with MFS, both of a child with MFS (data not shown).

| Marfan syndrome characteristics in the children
The diagnosis MFS was molecularly confirmed in 42 of the 43 children.
T A B L E 1 Sociodemographic characteristics of parents of a child with MFS; control-group parents of a healthy child; children with MFS; and control-group healthy children

| Overall distress
Overall distress scores are shown in Table 2. The median overall distress score (IQR) of mothers of a child with MFS was significantly lower compared to control-group mothers (2, 1-4 vs. 3, 1-6; p = .049; r = −.07). Mothers without MFS reported significantly less overall distress compared to mothers with MFS, both of a child with MFS (1, 0-4 vs. 3.5, 2-5; p = .039; r = −.17). No significant differences in overall distress were found between the other groups.

| Clinical distress
Clinical distress scores are shown in

| Everyday problems
Total and everyday problem domain scores are shown in Table 3

| Everyday problem items
Everyday problem items are shown in Table 3.
When looking at the everyday problem items within the 6 problem domains, mothers of a child with MFS reported significantly less often everyday problems on the items finances (0 vs. 16.7%, p = .001, n = 0 in a cell, no OR calculation possible); dealing with (

| Support from others
Mothers and fathers without and with MFS of a child with MFS, living together with a healthy or an affected partner did not differ significantly from control-group parents with respect to experiencing to receive enough support from surroundings, experiencing a lack of understanding from others and the wish to talk with a professional about their situation (Table 3). Both mothers and fathers of a child with MFS indicated more often to have a chronic illness than parents of a healthy child (40 vs. 20%, p = .002, OR = 2.7, 95% CI 1.40-5.0; 64 vs. 14%, p = .000, OR = 11.11, 95% CI 4.55-25.0, Table 3).

| Associations of distress and Marfan syndrome characteristics of children
There were no significant associations between distress on the one side, and the revised Ghent systemic score of the child, the childreported pain and/or fatigue on the other side.

| DISCUSSION
This study is the first quantitative study reporting on distress and everyday problems in mothers and fathers without and with MFS parenting a child with MFS. Surprisingly, parents of a child with MFS did not show more signs of clinical distress than parents of healthy children. The total group of mothers of a child with MFS even reported significantly lower overall distress and everyday problems compared to control-group mothers, albeit with small effect sizes.
This was an unexpected finding given the well-known risk of (acute) medical MFS related complications (Dietz, 1993  Note: Significant differences at p < .05 are presented in bold; distress and domain scores: numerical data > not normal distributed > Mann-Whitney U tests with Z score (z) and effect size (r); binary data > Chisquare tests with odds ratio (OR) and confidence interval (CI). Abbreviations: IQR, interquartile range; MFS, Marfan syndrome; p value, probability value; OR, odds ratio; r, effect size; n, number.
a Total problem score = the sum of item scores (yes = 1, no = 0) within 6 problem domains (practical, social, emotional, physical, cognitive and parenting). T A B L E 3 DT-P everyday problem-item scores of mothers and fathers of a child with MFS compared to control-group mothers and fathers of healthy children  (Cousino & Hazen, 2013) and parental burden (Biber et al., 2019;Jackson et al., 2015;Jackson et al., 2018). In previous studies in which parental distress was measured by the DT-P compared to control-group parents, high overall distress and everyday problems were found in parents of children with cancer (Schepers et al., 2018), mucopolysaccharidosis type III (Conijn et al., 2019), and in children needing home parenteral nutrition .
In parents of children with Inflammatory Bowel Disease (Diederen et al., 2018), a worsening disease course was directly associated with increased distress. In MFS, however, the clinical features evolve during life, and high-risk complications or surgery, are only infrequently encountered during childhood. The low level of medical emergencies requiring hospital visits or hospitalization in MFS in childhood may partly explain why we did not find elevated distress nor any association between distress and the child's revised Ghent systemic score, child-reported pain and/or fatigue. However, medical professionals should be aware that whenever acute medical complications arise, for example, lens luxation, pneumothorax, aortic rupture, musculoskeletal surgery or other surgery in a child or a parent with MFS, distress levels in parents might become clinically relevant and should be addressed accordingly.
Another hypothesis for the unexpected results of our study might be that the parents had developed strong coping strategies. The term "coping" is defined as "the thoughts and behaviors used to manage the internal and external demands of situations that are appraised as stressful, so that it is possible to live and deal with stressful situations and reduce internal and external conflicts and demands" (Folkman & Lazarus, 1980). This is endorsed by a review reporting on psychosocial factors in adults with MFS; despite the psychologically distressing aspects of the diagnosis MFS, most patients were able to manage their stressors and exhibited a higher than average life satisfaction because of efficient coping and reliance on self-efficacy (Nielsen et al., 2019). In our recent qualitative paper, adolescents with MFS also described positive coping strategies as seeking social support, having a humorous and relaxed outlook on life, reappraising their disease and disability in a positive light, pursuing a healthy lifestyle, and trying to plan their activities well to handle the impact of MFS on their physical and psychosocial functioning (Warnink-Kavelaars, Beelen, Goedhart, et al., 2019). These adolescents may have copied these strong coping strategies from their parents or the parents may have adopted these strategies from their child.
Little is known about the impact on distress and everyday problems in parents, of parenting a child with a connective tissue disorder (e.g., MFS, Ehlers Danlos, Loeys Dietz syndrome) and being affected by the same disorder or caring for an affected partner and an affected child. In our study, although not significantly different, mothers with MFS tended to report higher clinical distress (50%) compared to control-group mothers (42%). It is known that in adults, MFS negatively affects family life, physical activities, psychosocial development, education, work, and reproductive planning (Nielsen et al., 2019;Peters et al., 2002;Velvin et al., 2015aVelvin et al., , 2016b. Furthermore having a chronic illness as a parent adversely affects parental health-related quality of life (Hatzmann et al., 2009;Hatzmann et al., 2014). In our study, healthy parents of a child with MFS, living together with an affected partner, did not show more signs of clinical distress compared to control-group parents of healthy children. However, these mothers reported significantly more often everyday problems on the item fears and fathers reported more often everyday problems on the items dealing with friends and interacting with your child(ren). Because of the negative impact of MFS in adults, for example, personal and family life, medical professionals should be extra alert for distress in parents of families with both a child and a parent with MFS.
Our study has some limitations. First, the sample size might have been too small to find more subtle differences between the groups.
Second, all parents were recruited from the Amsterdam Expert Center for children with Marfan syndrome and related disorders. Third, not for every child both parents filled in the questionnaire. One may argue that the one parent with the least problems of the two was more likely to fill in the questionnaire. Also, the DT-P is linked to the child's hospital visit and asks questions concerning distress in the past week.
Parents with MFS with medical complications themselves, busy family schedules, other problems or elevated distress might have canceled the appointment. Therefore, the data may underestimate the distress and everyday problems.
In conclusion, parents of a child with MFS did not show more clinical signs of distress compared to parents of healthy children. Mothers of a child with MFS even reported less overall distress and total everyday problems screened by the DT-P. The distress in parents was not associated with the children's revised Ghent systemic score, childreported pain and/or fatigue.
However, clinical distress was reported in approximately onethird of parents and may further increase in case of acute medical complications in the child or parent with MFS. We, therefore, advise monitoring distress in parents of a child with MFS so that targeted support can be provided whenever indicated.

ACKNOWLEDGMENTS
We thank the parents who participated in this study. We are grateful