Measuring economic burden in families of individuals with Angelman Syndrome in Poland: a caregivers’ survey

TL;DR

Caring for individuals with Angelman Syndrome in Poland is financially overwhelming for families, with out-of-pocket costs and lost income exceeding public support.

Contribution

This study quantifies the economic burden of Angelman Syndrome caregiving in Poland for the first time.

Findings

Average annual out-of-pocket costs per household were $69,511, exceeding public reimbursement by over $22,000.

Caregivers lost an average of $31,809 in income due to caregiving, with minimal professional or informal support.

Public aid did not offset the full economic impact, especially indirect costs like reduced employment.

Abstract

Angelman Syndrome (AS) is a rare neurogenetic disorder characterized by severe intellectual disability, seizures, and motor and speech impairments, requiring lifelong, intensive care. Although caregivers of individuals with AS often face reduced quality of life and substantial emotional and financial strain, little is known about the cost-of-illness in Poland. To address this gap, we conducted a cross-sectional study in collaboration with the Foundation for Angelman Syndrome Therapeutics Poland (FAST Poland). An anonymous web-based survey was completed by 85 parents of individuals with AS to assess the 12-month financial burden of caregiving, including healthcare utilization, non-medical expenses, caregiver-related health costs, and broader socioeconomic impacts.

The average annual out-of-pocket cost per household was $69,511, which far exceeded the average public reimbursement of $46,928. Major private expenditures included therapy and rehabilitation ($7,836), non-reimbursed rehabilitation camps ($4,451), and medical equipment ($2,637). Income loss due to caregiving averaged $31,809 per household, contributing significantly to the overall burden. Psychological support and medication for caregivers generated additional costs, often paid entirely out of pocket. Spearman’s correlations revealed that younger patients incurred higher hospitalization and private rehabilitation expenses, while older individuals required more home modifications. Caregiving averaged 89.4 h per week, with minimal professional or informal assistance. Despite most families receiving public support, it did not offset the full economic impact, particularly indirect costs such as reduced employment. The findings underscore the chronic, high-cost nature of AS caregiving in Poland, marked by insufficient systemic support and reliance on family-provided, unpaid care.

AS imposes a major financial burden on families, as out-of-pocket expenses and income loss surpass public aid. These findings underscore the urgent need for improved systemic and policy-level support for caregiving.

Full text

Background

Angelman Syndrome (AS) (ICD-10: Q93.51, ICD-11: LD90.0, ORPHA: 72, OMIM: 105830) is a rare neurogenetic disorder [1, 2]. With a prevalence of approximately 1 in 12,000 to 20,000 individuals, it is estimated that AS affects approximately 500,000 people worldwide [3, 4], including 145 individuals registered in the Global Angelman Syndrome Registry from Poland [5]. AS results from several distinct genetic mechanisms, most commonly a maternal 15q11.2–q13 deletion (70–75%), followed by pathogenic variants in the maternal UBE3A gene (~ 15%), paternal uniparental disomy (5–7%), and imprinting defects (5–7%); mosaicism occurs rarely and is usually associated with an epimutation [1]. These genetic differences significantly influence both the clinical severity and caregiving demands related to the condition [6].

While different genetic mechanisms may lead to distinct phenotypic variations, all forms of AS share core clinical features [7, 8]. The syndrome is typically marked by severe intellectual disability, motor and balance impairments, absent or minimal speech, epilepsy, and sleep disorders [9–12], along with craniofacial features like microcephaly, prognathism, macroglossia, and deep-set eyes [9, 13, 14]. A distinct behavioral phenotype includes frequent laughter, hand flapping, tremors, hyperactivity, attention difficulties, feeding problems, drooling, and aggressive or self-injurious behaviors, as well as a fascination with water [9, 13, 15]. Common comorbidities include scoliosis, gastrointestinal symptoms, and autism spectrum disorder [11, 16].

Due to its heterogeneous presentation, AS is often misdiagnosed, prolonging the diagnostic process [10, 16–20]. Therefore, confirmation of the diagnosis requires genetic testing (e.g., methylation analysis, MS-MLPA, microarrays, FISH, or UBE3A gene sequencing) [14, 21]. Although there is no curative treatment, research is ongoing, and current care is supportive, involving medication, rehabilitation, and multidisciplinary therapies [22–24]. Consequently, in addition to regular rehabilitation and, frequently, hospital stays, people with AS need continuous, comprehensive, multidisciplinary home-based care [10, 25]. Simultaneously, while life expectancy in AS is generally normal, risks such as sudden unexpected death in epilepsy (SUDEP) and sudden unexpected death in sleep (SUDS) may shorten it by 10–15 years [26–28].

For all these reasons, families must provide constant, intensive support, often leading to physical (e.g., fatigue, injury), mental (e.g., depression, anxiety), and social burdens (e.g., isolation) [29–33]. As a result, caregivers often experience stress, lower quality of life, and greater psychological vulnerability than those caring for children with other neurodevelopmental or rare syndromes [34–37], frequently requiring psychiatric care [10, 16–20]. Financial strain is also considerable and includes frequent visits to healthcare professionals, the need for health-related consumables, varying out-of-pocket expenses, and disparities in insurance coverage depending on the national healthcare system. Many parents are compelled to reduce their working hours or leave the workforce entirely [6, 10, 30, 32, 34, 38–40]. Studies consistently show that AS imposes substantial economic burdens on families, driven by both direct costs (e.g., therapies, equipment, home modifications) and indirect costs (notably caregiver productivity loss). For example, in the U.S., the average annual cost per individual with AS was estimated at nearly 80,000, with over half attributed to lost productivity [[41](#CR41)]. In Australia, parents of individuals with AS were found to lose over 38% of their productivity-adjusted life years, resulting in a societal cost of AUD45.3 million, with mothers bearing the majority of the burden due to reduced employment [39]. These financial strains are compounded by the negative impact of caregiving on parents’ physical and mental health, further affecting their quality of life and economic stability.

Despite growing international knowledge, little is known about the specific cost-of-illness associated with AS in Poland. Recent studies suggest that while diminished quality of life and caregiver burden among parents of children with AS are often linked to the diagnostic odyssey and its perceived impact on the child’s health, financial well-being is the strongest single predictor of reduced quality of life and increased burden in caregivers [33]. Therefore, this study aims to evaluate the cost-of-illness related to caregiving for individuals with AS in the Polish context.

Methods

Study design

Given the sensitive and socially significant nature of the study, it was designed as a patient-oriented survey [42, 43] and was developed in collaboration with the patient advocacy organization Fundacja Foundation for Angelman Syndrome Therapeutics Poland – FAST Poland (https://www.cureangelman.pl), which actively participated in all phases of the study’s design and implementation. This ensured that the study addressed caregiver-identified priorities and enabled active engagement of caregivers as research partners.

In cooperation with the Foundation, an anonymous, computer-assisted, web-based self-reported survey was developed using Microsoft Forms (Microsoft 365 platform) to assess the direct and indirect financial costs of caring for a person with AS, including healthcare utilization, non-medical expenditures, health-related costs for caregivers, and the broader social and economic burdens on families.

The study was approved by the Bioethics Committee of the Poznan University of Medical Sciences (KB – 660/24, issued on October 9, 2024) and received additional acceptance from the board of FAST Poland.

Participants

Because AS is a rare condition and Poland lacks a national patient registry, FAST Poland assisted in participant recruitment by inviting caregivers through internal communication channels. Given the absence of national epidemiological data, as no authoritative national rare disease registry exists in Poland, and there are no precise epidemiological data on the prevalence of AS in the Polish population, the target sample size could only be estimated pragmatically. Eligible participants were included if they were over 18 years old, were parents or primary family caregivers of an individual with a molecularly confirmed diagnosis of AS, were Polish, had access to the Internet Patient Account (Internetowe Konto Pacjenta – IKP) system, were able to use electronic devices for online participation, and provided written informed consent.

Questionnaire

The development of the questionnaire was guided by a literature review and a focus group interview with three mothers of children with AS. In addition, the structure of cost categories was informed by established cost-of-illness frameworks and previous economic evaluations in AS and other rare neurogenetic disorders [39–41, 44–46]. The tool aimed to evaluate caregivers’ assessment of the cost-of-illness in AS and the health expenditures associated with caregiving.

A pilot test was conducted with five parents to evaluate the questionnaire’s clarity and relevance, and these pilot responses were not included in the final analysis. The survey retrospectively explored how caregiving affected respondents in several key areas: (1) direct medical expenses related to caring for a person with AS in the past 12 months (January 1 to December 31, 2024), whether covered by the National Health Fund (Narodowy Fundusz Zdrowia – NFZ) or paid out-of-pocket (e.g., hospitalizations, medications, specialists’ visits, rehabilitation and therapy, medical equipment, etc.); (2) indirect medical expenses (e.g., travel, private services, costs of parent’s stay during hospitalization, etc.); (3) health-related costs for caregivers over the same 12-month period, including both reimbursed and privately funded psychological and psychiatric care, as well as any additional health-related expenditures; and (4) direct and indirect non-medical expenses (lost income due to job resignation, extra electricity, heating, water, home modifications, additional insurance). Additionally, the questionnaire included questions on caregiver demographics and the demographic and clinical profile of the person with AS, including age, sex, clinical symptoms, comorbidities, and general medical condition.

Clinical characteristics, symptoms, and comorbidities of individuals with AS were collected through caregiver self-report as part of the structured online questionnaire. Respondents provided information based on their own knowledge, supported where possible by data retrieved from the Internet Patient Account (IKP) and their personal medical documentation. The list of symptoms and comorbidities was informed by previous AS studies, international clinical descriptions (ICD, OMIM, Orphanet), and consultation with FAST Poland, but was not derived from a formal AS disease concept model.

The questionnaire was filled out retroactively by participants, who entered information from the IKP system to assess the impact of caring during the previous 12 months.

Data collection

Data were collected between January and February 2025 via FAST Poland’s internal mailing lists, social media platforms, and official website. In the initial phase, participants received an invitation letter introducing the research team and outlining the study’s aims, methodology, and plans for data dissemination. The letter also highlighted the voluntary, anonymous, and confidential nature of the survey.

Next, all eligible participants were provided with instructions on how to navigate the IKP system and complete the questionnaire. Advance notice of the study’s scope enabled participants to prepare information for the economic evaluation of their caregiving experiences, either by locating relevant receipts, notes, or records documenting privately funded procedures or by retrieving data from their IKP account. Access to the web-based questionnaire was granted after participants submitted electronic informed consent, in accordance with the Declaration of Helsinki. No financial incentives were offered for participation. To avoid duplicate reporting, only one caregiver per household was included, and each questionnaire represented a single household.

Data analysis

Descriptive statistics were calculated to summarize demographic characteristics, service utilization, and cost data. Continuous variables are presented as means with standard deviations (SD), medians, and ranges, while categorical variables are reported as counts and percentages. Associations between patient age and both reimbursed and out-of-pocket service utilization or expenditures were assessed using Spearman’s rank correlation coefficient (ρ), with corresponding 95% confidence intervals (CI). All analyses were two-tailed, and statistical significance was set at p < .05. Analyses were conducted using JASP software (version 0.19.3; JASP Team, Amsterdam, The Netherlands).

All cost data were initially collected in the local currency (Polish złoty, PLN), but are presented in international dollars ($) in the tables. Currency conversion was based on Purchasing Power Parity (PPP) using 2024 rates, with an exchange rate of 1$ = 1.9 PLN (estimate as of June 17, 2025), in line with the methodology of the International Monetary Fund [47]. PPP is an economic approach that compares the relative value of currencies by measuring the amount of goods and services they can purchase. It adjusts for price level differences between countries, allowing for a more accuratAdditionally, the questionnairee comparison of economic indicators like income and expenditure. By using PPP, we account for local cost-of-living variations, enabling a comparison of economic data based on real purchasing power rather than nominal exchange rates.

Results

Because national epidemiological data on AS are unavailable, it was not possible to determine the exact proportion of Polish families represented in this sample. A total of 85 caregivers participated in the survey. According to internal estimates from FAST Poland, the age and gender distribution of our survey population appears broadly consistent with that of the known Polish AS community, suggesting that the sample is reasonably representative in these key demographic characteristics. However, caregivers of the three oldest individuals in the Registry (aged 40, 33, and 32 years) did not participate, likely due to limited use of the Internet Patient Account (IKP) system among older caregivers. Most caregivers were female (92.9%), with a mean age of 39.4 years, and 45.9% were professionally active (Table 1). Individuals with AS had a nearly equal sex distribution and a mean age of 8.7 years. The most common genetic diagnosis was a 15q11–q13 deletion (80%). Nearly all patients exhibited core AS symptoms such as psychomotor delay (97.6%), intellectual disability (94.1%), speech impairment (95.3%), motor and balance disorders (97.6%), and abnormal muscle tone (96.5%). Frequent comorbidities included ophthalmologic (72.9%), orthopedic (74.1%), gastrointestinal (68.2%), behavioral, and sensory issues, including, short attention span (92.9%), sensory integration difficulties (88.2%), sleep disturbances (84.7%), hyperactivity (77.6%), excessive biting or oral self-stimulation (77.6%), and features associated with autism spectrum disorder (41.2%). In the year before the survey, 51.8% of parents reported varying frequencies of seizures in their children. Additionally, the diagnostic process was often prolonged and complex: while the median time to obtain a correct diagnosis was 1.5 years, 48.2% of patients received at least one misdiagnosis.

Table 1. Demographic characteristics of the survey populationCharacteristicsN (%) AS caregivers  Sex  female79 (92.9)  male6 (7.1) Age (in years)  Range29–55  Mean (SD)39.4 (6.3)  95%CI for mean38-40.7  Median39 Professional activity  yes39 (45.9)  no46 (54.1) AS patients  Sex  female42 (49.4)  male43 (50.6) Age (in years)  Range1–26  Mean(SD)8.7 (5.4)  95%CI for mean7.5–9.9  Median8 Genotype determined at diagnosis  deletion of the 15q11-q13 region68 (80)  UBE3A gene mutation8 (9.4)  uniparental disomy (UPD)4 (4.7)  imprinting centre defect2 (2.4)  other3 (3.5) Symptoms present in a person with AS   delayed psychomotor development83 (97.6)  intellectual disability80 (94.1)  severe speech impairment or complete lack of verbal communication81 (95.3)  seizures67 (78.8)  motor and/or balance disorders (i.e., ataxia, coordination problems)83 (97.6)  muscle tone disorders82 (96.5)  strabismus, other ophthalmologic problems62 (72.9)  orthopaedic problems (i.e., scoliosis, contractures, foot abnormalities)63 (74.1)  gastrointestinal disorders (reflux, constipation)58 (68.2)  feeding/eating difficulties and/or challenges (e.g., food selectivity, ARFID, etc.)35 (41.2)  excessive biting/oral self-stimulation, including use of inedible objects66 (77.6)  sucking/swallowing (dysphagia) / chewing difficulties51 (60)  overweight / obesity19 (22.4)  abnormal sleep-wake cycles and sleep disturbances72 (84.7)  hyperactivity, restlessness66 (77.6)  atypical or inappropriate behaviour (i.e., excessive laughter)55 (64.7)  short attention span79 (92.9)  autism spectrum disorders35 (41.2)  sensory integration disorders75 (88.2)  self-injurious or aggressive behaviour30 (35.3) Did the patient have seizures in the past year?   yes, less than 1023 (27.1)  yes, between 10 and 209 (10.6)  yes, over 2012 (14.1)  no41 (48.2) Time spent before the correct diagnosis was made(in years)   Range0.1–15  Median1.5  *Mean(SD)*2.5(3) Number of misdiagnoses   041 (48.2)  122 (25.9)  211 (12.9)  34 (4.7)  44 (4.7)  5+3 (3.5)

Table 2 summarizes the specialist medical and therapeutic services used by individuals with AS in 2024. Nearly all patients received care from neurologists (95.3%) and paediatrician or general practitioners (89.4%), with frequent consultations from rehabilitation physicians (69.4%), ophthalmologists (63.5%), and dentists (65.9%). Psychological support was accessed by 55.3% of patients, while visits to psychiatrists, dietitians, and other specialists were less common (23.5%, 18.8% and 11.8%, respectively).

All individuals received physical rehabilitation, with high use of speech therapy (91.8%), AAC methods (71.8%), sensory integration (82.4%), and occupational therapy (60%). Psychological therapy (57.6%), hydrotherapy (50.6%), and animal-assisted therapy (45.9%) were also notable. Less common were manual therapy, osteopathy, and feeding therapy.

Table 2. Specialist medical and therapeutic services utilized by individuals with AS in 2024 (January 1, 2024–December 31, 2024)CharacteristicsN (%) Specialist care received by the person with AS during the past year  neurologist81 (95.3) geneticist27 (31.8) psychologist47 (55.3) psychiatrist20 (23.5) orthopaedist34 (40) dietitian16 (18.8) gastroenterologist17 (20) ophthalmologist54 (63.5) otolaryngologist (ENT specialist)37 (43.5) rehabilitation physician59 (69.4) gynaecologist3 (3.5) dentist56 (65.9) cardiologist10 (11.8) paediatrician / primary care physician (GP)76 (89.4) other Types of therapy utilized by the person with AS during the past year  physical rehabilitation/physiotherapy85 (100) psychological therapy49 (57.6) occupational therapy51 (60) speech / neurospeech therapy78 (91.8) augmentative and alternative communication (AAC)61 (71.8) feeding therapy9 (10.6) manual therapy29 (34.1) sensory integration therapy70 (82.4) sleep training0 osteopathy18 (21.2) animal-assisted therapy (zootherapy)39 (45.9) hydrotherapy, swimming/water therapy (with or without hydrotherapy)43 (50.6) other10 (11.8)

Table 3 outlines the socioeconomic status and caregiving support in households of individuals with AS. Most families had only one income earner (63.9%), and 36.5% reported having no cash savings, while 51.8% were regularly repaying debts or other financial obligations. At the same time, 96.3% of families reported receiving financial support from the government and local government institutions, with an average amount of $19,745.

Caregiving demands were high, averaging nearly 90 h per week (median: 97 h), while external support was minimal; both professional and informal care averaged close to zero, at 3.9 and 5.7 h per week, respectively. These findings highlight families’ strong dependence on unpaid, family-based care with little outside assistance.

Table 3AS household socioeconomic characteristics and caregiving supportCharacteristicsN (%) Number of household members with regular income  01 (1.2) 156 (63.9) 228 (32.9) The household has cash savings  yes54 (63.5) no31 (36.5)The household has instalments,* loans*,* debts*,* credits*,* or arrears* (e.g., rent, electricity, telephone, back taxes) to pay? yes, but we are repaying them regularly44 (51.8) yes, and we’re having trouble repaying them6 (7) no35 (41.2) Number of hours per week spent on caregiving  Range2-168 Median97 Mean(SD)89.4 (45.2)Number of hours per week of professional carer (e.g.,* nurse*,* social worker*,* disability assistant*,* etc.)* Range0–45 Median0 Mean(SD)3.9 (9.3)Number of hours per week of unpaid care from informal carers (e.g.,* family member*,* distant relative*,* neighbours*,* volunteer)* Range0–68 Median0 Mean(SD)5.7 (11.4) Total monetary value of assistance from the government and local government institutions  number of caregivers who received support82 (96.3) the average amount of financial support receivedUS$19,745

Table 4 presents annual healthcare expenditures for individuals with AS and their caregivers in 2024, divided into public reimbursements and out-of-pocket costs. Public healthcare expenditures reimbursed by the NFZ were reported for all 85 patients, with the most common reimbursements covering medications (91.8%, $708 annual cost per patient), hospitalizations (60$9,162), and rehabilitation or therapy (63.5%, $3,159). Other reimbursed services included specialist visits (75.3$699), professional caregiving (36.5%, $2,263), rehabilitation camps (17.7$312), and medical equipment (62.4%, $1,032). Car-related expenses were reimbursed for 21.2$437). Caregiver-related reimbursements included psychological or psychiatric care (38.8%, $267), rehabilitation (15 individuals,$14), and psychiatric medications (15 individuals, $19). The total average reimbursed cost per patient was$46,928. Additionally, while nearly all children attended special needs schools, the average educational costs reimbursed by the government and local government institutions totaled $28,856.

Out-of-pocket expenditures placed a heavy burden on AS families. Common costs included supplements (97.6%, $982 annual cost per-patient), therapy and rehabilitation (88.2$7,836), and medical equipment (85.9%, $2,637). Over half of patients (55.3$4,451 per patient), and 81.2% had private specialist visits ($903). Other frequent expenses (83.5$2,154). Caregivers incurred additional costs for psychological support (32.9%, $617), rehabilitation (49.4$536), and psychiatric medications (15.3%, $212).

Indirect costs added to the economic burden of caregiving: transport expenses affected 88.2% of households ($2,126 annual cost per-patient), and 65.9$31,809. Informal care was valued at $6,207 annually in 48.2$4,292). Other indirect expenses included increased utility bills (89.4%, $447), caregiver support (58.8$1,109), and insurance (40%, $505).

Overall, the average annual out-of-pocket cost per household was $69,511, highlighting the substantial economic impact of AS beyond publicly funded care.

Table 4. Annual healthcare expenditures for AS patients and caregiversCategoryPatientsN (%)Value per patient (US$)Average annual public healthcare expenditure in 2024 (January 1,** 2024-December 31**,** 2024), reimbursed by the National Health Fund**,** the government**,** and local government institutions** Reimbursed direct medical costs for AS patient  hospitalizations51 (60%)9,162 medications78 (91.8%)708 specialists’ visits64 (75.3%)699 rehabilitation and therapy54 (63.5%)3,159 paid professional care, e.g., nurse, social worker, disability assistant, etc.)31 (36.5%)2,263 rehabilitation camps15 (17.7%)312 medical equipment, e.g., wheelchairs, medical beds, walking frames, walkers, standers, orthoses, orthopaedic shoes, etc.53 (62.4%)1,032 car customization/purchase18 (21.2%)437 increased educational costs related to fulfilling compulsory schooling requirements, associated with a severe degree of disability.83 (97.6%)28,856 Reimbursed direct medical costs for the caregiver  psychiatrist or psychologist support for the caregiver33 (38.8%)267 rehabilitation and therapy for the caregiver, e.g., physiotherapist, orthopaedist, etc.15 (17.6)14 psychiatric drug therapy15 (17.6)19 Total costs reimbursed by the National Health Fund and the state budget 85 (100%)46,928Average annual out-of-pocket healthcare expenditure in 2024 (January 1,** 2024–December 31**,** 2024)** Out-of-pocket direct medical costs for an AS patient  non-reimbursed medications63 (74.1%)713 supplements83 (97.6%)982 specialists’ visits, e.g., dentist, geneticist, neurologist, psychiatrist69 (81.2%)903 rehabilitation and therapy75 (88.2%)7,836 rehabilitation camps47 (55.3%)4,451 other expenses, e.g., special food, special clothing, bibs, legal fees for care, medical toys, etc.71 (83.5%)2,154 paid professional care, e.g., nurse, social worker, disability assistant, etc.)16 (18.8%)482 medical equipment, e.g., wheelchairs, medical beds, walking frames, walkers, standers, orthoses, orthopaedic shoes, etc.73 (85.9%)2,637 car customization/purchase32 (37.6%)1,269 Out-of-pocket direct medical costs for the caregiver  psychiatrist or psychologist support for the caregiver28 (32.9)617 rehabilitation and therapy for the caregiver, e.g., physiotherapist, orthopaedist, etc.42 (49.4)536 psychiatric drug therapy13 (15.3)212 Out-of-pocket indirect costs  transport costs/travel expenses to hospital/examinations, rehabilitation75 (88.2%)2,126 costs of parents’ stay during hospitalization29(34.1%)224 extra electricity, heating, water76 (89.4%)447 lost income due to job resignation56 (65.9%)31,809 value of informal care (family, neighbours)41 (48.2%)6,207 home modifications46 (54.1%)4,292 non-reimbursed caregiver support50 (58.8%)1,109 additional insurance34 (40%)505 Total private expenditures 85 (100%)69,511

Table 5 presents Spearman’s rho correlations between the age of individuals with AS and the utilization or cost of various health services. Younger age was significantly associated with more frequent hospitalizations (ρ = − 0.430, p < .001), while older individuals were more likely to receive reimbursed professional care from the NFZ (ρ = 0.268, p < .05).

Among out-of-pocket expenses, older age correlated with lower spending on private doctor visits (ρ = − 0.269, p < .05), private rehabilitation (ρ = − 0.370, p < .001), transportation (ρ = − 0.296, p < .01), parental accommodation (ρ = − 0.246, p < .05), and informal care (ρ = − 0.271, p < .05), reflecting a shift in caregiving patterns and care intensity over time. In contrast, home modification costs increased with age (ρ = 0.252, p < .05), suggesting these adaptations accumulate or become more necessary as children grow older.

No significant age-related correlations were found for other categories, such as supplements, medical equipment, or therapeutic camps. Overall, age emerged as a key factor influencing care patterns and related costs in AS.

Table 5. Spearman’s Rho correlation between patients’ age and the utilization or cost of healthcare services (reimbursed and out-of-pocket)ρ95%CI p Patient’s agehospital stays-0.430-0.593; -0.232 < 0.001 Patient’s agereimbursed medications0.013-0.225; 0.249nsPatient’s agereimbursed specialists-0.165-0.404; 0.095nsPatient’s agereimbursed rehabilitation0.130-0.124; 0.368nsPatient’s agereimbursed care0.2680.056; 0.457 < 0.05 Patient’s agereimbursed therapeutic camps0.038-0.182; 0.254nsPatient’s agereimbursed equipment costs0.154-0.079; 0.371nsPatient’s agenon-reimbursed medications-0.061-0.272; 0.155nsPatient’s agesupplements-0.083-0.292; 0.134nsPatient’s ageprivate doctor visits-0.269-0.457; -0.0.58 < 0.05 Patient’s ageprivate rehabilitation-0.370-0.541; -0.169 < 0.001 Patient’s ageprivate therapeutic camps-0.137-0.334; 0.091nsPatient’s ageother expenses-0.152-0.357; 0.067nsPatient’s agepaid care-0.153-0.356; 0.063nsPatient’s ageprivate medical equipment-0.127-0.334; 0.091nsPatient’s agetransportation costs-0.296-0.481; -0.086 < 0.01 Patient’s ageparent accommodation expenses-0.246-0.439; -0.032 < 0.05 Patient’s agevalue of informal care-0.271-0.459; -0.061 < 0.05 Patient’s agehome modifications0.2520.037; 0.444 < 0.05 Statistically significant differences are written in boldface; ns: not significant

Discussion

The results of this study highlight the substantial financial burden faced by families of individuals with AS, underscoring systemic gaps and the urgent need for targeted policy interventions. While previous studies have identified financial well-being as the primary factor linked to reduced quality of life and increased burden among AS caregivers [33, 41], our findings demonstrate that the caregiving demands themselves constitute a significant source of financial strain for families. Out-of-pocket expenses significantly exceed public healthcare reimbursements, a disparity further exacerbated by frequent income loss due to job resignation. Although a significant proportion of parents receive financial support from the government and local government institutions, these funds do not compensate for the lost income caused by the inability to work. This underscores the pronounced financial vulnerability and systemic under-support experienced by affected families. A major cost of caring for an individual with AS is the school care provided by the state in special needs institutions. Additionally, the findings indicate that a patient’s age significantly affects healthcare utilization and related costs. Younger individuals incur more hospitalizations and private rehabilitation expenses, whereas older individuals receive more reimbursed care and generate higher out-of-pocket costs for home adaptations. This suggests that care needs and their economic consequences evolve over time, and that different life stages may have varying impacts on the financial situation of caregivers. Similarly, reimbursed expenditures also shift with the patient’s age, resulting in a temporally uneven distribution of costs covered by public funds.

These findings align with global data on rare diseases’ economic burden. In 2019, 379 rare diseases in the U.S. cost $997 billion, with direct medical costs at$449 billion (45%). Hospitalizations (32%) and prescription drugs (18%) were major direct costs. Indirect costs from productivity loss totaled $437 billion (44$149 billion, 34%), presenteeism ($138 billion, 32$136 billion, 31%). Non-medical costs were $73 billion (7$38 billion (4%). Average annual medical cost per patient was $28,913, highest in children ($32,037), lowest in those over 65 (27,157) [[46](#CR46)]. Another U.S. study of 24 rare diseases (584,000 patients) estimated 125 billion annual societal costs; average per patient $266,000 (10 times common diseases’$26,000). Highest costs: metabolic ($334,000) and neurological ($317,000). Lack of treatment increased costs by 21.2% (2.2%–51.8%). Direct costs: $63,000 with treatment vs.$118,000 without. Non-medical costs (5–10%), indirect costs $40,000 with treatment and$73,000 without, making up 40–45% of the total. Mortality costs: $36,000 with treatment,$49,000 without. Total cost for 8.4 million U.S. rare disease patients estimated at $2.2 trillion annually vs.$3.4 trillion for 133 million with common diseases [48]. However, expanding the scope beyond Western countries, similar patterns of economic burden are reported in other regions. For example, a study of 16,945 individuals (8,454 adults, 8,491 children) with 33 rare diseases in China reported annual costs as a percentage of household income: direct medical 105.12%/103.22%, direct non-medical 40.82%/45.30%, indirect 20.98%/22.86% (adults/children). Most experienced high burden (70.2% adults, 57.3% children), followed by low burden (28.7% adults, 42.5% children) and extremely high burden (1.1% adults, 0.2% children). Risk factors for very high burden included older age, poverty, low socioeconomic status, delayed diagnosis, comorbidities, and active treatment; poverty increased the odds of very high burden up to OR 50.37 in adults [49].

Our findings confirm that AS imposes significant economic strain, stemming from both direct and indirect costs of lifelong caregiving. The highest reimbursed medical expenses were hospitalizations ($9,162 per patient annually) and rehabilitation or therapy ($3,159), while the most burdensome out-of-pocket costs were therapy and rehabilitation ($7,836) and medical equipment ($2,637). This is in line with a recent study by Jarvis et al., conducted among 105 caregivers of individuals with AS in the United States, which reported a mean annual economic burden of $79,837 per household (SD =$55,505). Healthcare expenses averaged $827 (SD =$2,072), including $399 for pharmaceuticals (SD =$1,123) and $428 for services (SD =$1,169). Out-of-pocket costs constituted a significant portion of the overall burden, averaging $29,680 (SD =$47,753), with major expenses for vehicle purchases or modifications ($6,717; SD =$17,791), professional care ($6,123; SD =$17,335), home modifications or repairs ($4,387; SD =$15,734), and supportive therapies, i.e. physical or speech therapy ($3,269; SD =$7,564). Additionally, lost leisure time was valued at $6,634 (SD =$4,652) [41].

However, similar financial strains have also been observed among parents of children with other rare neurological disorders. For instance, in EU5 countries, the annual direct medical cost per patient with Dravet syndrome was estimated at nearly $16,000, with approximately 50$27,000, largely due to hospitalizations (42%), while indirect costs reached up to $80,000 annually [51]. Another German study reported total direct healthcare costs of approximately €20,000 and indirect costs around €18,000 [52]. Irwin et al. calculated annual costs at €24,944 in direct expenditures, along with €17,594 in maternal and €1,565 in paternal indirect costs [53]. National studies also illustrate significant variability in costs related to specific rare diseases. A Polish study on adult cystic fibrosis patients estimated the average annual treatment cost at €900,729.78 (€19,581.08 per patient), with 70% direct and 30% indirect costs. Of the direct costs, 74% (€467,876.66; €10,171.23 per patient) were for pharmacotherapy, 21% (€132,402.94; €2,878.33 per patient) for hospitalization, with diagnostics (€28,677.93; €623.43 per patient) and outpatient visits (€3,098.03; €65.76 per patient) comprising the remainder. Indirect costs due to productivity loss totaled €262,478.43 (€5,706.03 per patient), and absenteeism costs were €3,536.00 (€76.89 per patient). Notably, indirect costs in Poland exceeded those in most other countries [54].

Finally, these economic burdens translate into significant societal and personal consequences, particularly impacting caregiver employment and productivity. Since more than half of the parents enrolled in this study reported unemployment resulting from caregiving, this study aligns with previous studies showing that high medical costs in AS are further compounded by frequent income loss due to job resignation among caregivers. An Australian study estimated that over 10 years, parents of individuals with AS lost 38.4% of their productivity-adjusted life years (PALYs), totaling 495.06 PALYs and a societal cost of AUD $45.3 million (USD$30 million). Significantly, mothers bore 63% of the burden due to reduced employment and workforce participation, losing 311.66 PALYs (1.50/person; 53.1%) vs. 183.40 PALYs for fathers (1.18/person; 25.2%). This translated into average productivity losses of AUD $145,007 per mother and AUD$128,252 per father. These losses were compounded by caregivers’ heightened physical, mental, and emotional strain [39]. Similarly, a recent study by Jarvis et al. found the average annual cost of AS caregiving to be nearly $80,000, with 53$43,000) due to productivity loss. Job-related impacts were reported by 83.8% of caregivers: 42.9% reduced hours, 35.2% left work for over a year, 24.8% couldn’t take a job, and 21.9% worked irregular hours [41].

Notably, in other rare neurogenetic disorders, elevated indirect costs, driven by job loss, reduced working hours, missed workdays, and loss of income, have also been identified as key predictors of parental depression and reduced quality of life. In France, among 85 parents of children with DS who reported employment difficulties, 33.3% were unemployed, and few worked full-time. Over 50% of mothers had interrupted their employment for more than six months, compared with just 7.1% of fathers [55]. Similarly, Campbell et al. found that 45% of caregivers had quit, retired early, or lost their jobs due to caregiving demands, and 18% had to change jobs [56]. Lagae et al. reported that 80% of EU5 caregivers experienced negative career impacts; among those unemployed (34%), 81% cited caregiving as the main reason. Among employed caregivers, 65% had missed work in the past month, with 28% missing more than three days [45]. Finally, 72% of Polish parents of children with DS reported work restrictions resulting from caregiving [57].

Importantly, mothers reported significantly greater productivity losses than fathers, reflecting a pronounced gender disparity in the caregiving burden. In France, over 50% of mothers had taken employment breaks longer than six months, compared with 7.1% of fathers [55]. In Germany, 31% of mothers quit their jobs (vs. 1% of fathers), 29% reduced working hours (vs. 6% of fathers), and 40% missed work in the preceding three months due to caregiving demands (vs. 27% of fathers) [52].

Limitations

While this study is the first effort in Poland to assess the self-reported economic burden of caring for individuals with AS, it is not without limitations. Firstly, the sample size of 85 respondents is relatively small. However, given the rarity of AS and the absence of a national rare disease registry, the exact number of affected families in Poland remains unknown. Moreover, considering that only 145 Polish individuals with AS are currently registered in the Global Angelman Syndrome Registry, the 85 household responses collected can be regarded as substantial. Another limitation stems from the retrospective nature of the study and the reliance on subjective caregiver reports, which could not be independently verified. Nevertheless, information about patients’ utilization of healthcare services and associated NFZ-reimbursed expenses was retrieved via the official Internet Patient Account (IKP). At the same time, it should be acknowledged that the IKP system, like any database, may contain occasional inaccuracies. Additionally, estimates of privately financed expenses may be prone to recall errors or incomplete records kept by some respondents. Additionally, household estimates of increased utility use (electricity, heating, water) were based solely on caregiver self-report, which may involve subjective judgment and recall limitations. Objective metering data were not available, and this constraint may introduce some imprecision into the calculation of these indirect costs. The web-based format of the survey could have also influenced participation; however, due to the absence of a centralized registry, recruitment through the patient organization FAST Poland, primarily using its website, social media, and mailing list, was the most feasible approach. Furthermore, the survey did not collect data on absenteeism (i.e., workdays or hours missed due to caregiving), presenteeism, or reduced workforce participation short of full resignation. These important dimensions of productivity loss fell outside the scope of the present study, partly due to the regulatory context in Poland until 2023, in which caregiver benefits were available only to individuals who fully resigned from employment. As a result, our ability to capture the full spectrum of labour-force impacts is limited. In addition, the survey did not collect data on the frequency of specialist care appointments, but only whether such consultations occurred within the previous year, which limits the ability to assess the intensity of specialist care use. An additional limitation of the study is the notable predominance of female respondents, which may introduce gender bias and limit the generalizability of the findings. However, it should be noted that the data were collected at the household level, meaning each response represents the entire family unit rather than just the individual respondent. Additionally, women are more often the primary caregivers and are significantly more likely to manage the household budget. Finally, no methodologically comparable estimates of the financial cost of raising a neurotypical child are available in Poland, which prevents direct benchmarking of the observed economic burden and further highlights the absence of national frameworks for evaluating family-level expenditures.

Conclusions

This study demonstrates a clear need for continuous, multidisciplinary medical and therapeutic support, with particularly high reliance on neurological, rehabilitative, and communication services. At the same time, families affected by AS face substantial caregiving demands, predominantly carried out by family members, with limited access to formal or informal support and a heavy dependence on unpaid care. The findings highlight the significant productivity burden associated with caregiving, especially for mothers, and emphasize the need for systemic recognition of these often-overlooked economic impacts. Altogether, the results underscore the profound and multifaceted burden AS places on families, not only through direct and indirect financial costs but also through substantial personal and professional consequences. These findings reveal critical gaps in current support systems and call for targeted policy and service-level interventions.