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Table 2 Key elements and challenges at different stages of life across PROS disorders

From: Mapping the PIK3CA-related overgrowth spectrum (PROS) patient and caregiver journey using a patient-centered approach

Stage of life Key elements and challenges
Across PROS Specific to K–T Specific to CLOVES Specific to M-CM
Birth to toddler Appearance of symptoms: vascular anomalies, port-wine stain, soft/bony tissue hypertrophy, asymmetrical overgrowth, enlarged head, macrodactyly
Challenge finding qualified specialists
Appearance of symptoms:
 Capillary malformations present as port-wine stains
 Venous malformations present as varicose veins
 Lymphatic malformations present as lymphedema
 Vast majority of extremity hypertrophy occurs in the leg
Appearance of symptoms: abnormal extremities, fatty truncal mass, vascular anomalies, skin abnormalities Appearance of symptoms: capillary malformations, “purple body,” webbed/extra digits, asymmetrical overgrowth, enlarged head, midline facial birthmark, low muscle tone
Toddler/preschool age Stigma concerns
Support devices for mobility
Exploring appropriate schooling options and support
Frequent illnesses
Support devices for mobility
Special clothing supplier/tailoring
Stigma concerns can arise due to greater interaction with other children
Begin thinking about schooling options
Watch for trauma/infections
Developmental/learning issues may begin to appear
Stigma concerns
Support devices for mobility
Exploring appropriate schooling options and support
Frequent illnesses
Developmental delays may appear or become more apparent
Support devices for mobility, communication
Exploring appropriate schooling options and support
Frequent illnesses
Elementary school Special accommodations at school
Missed school/work due to appointments and surgeries
Physical limitations
Stress from looking different, being stared at
Frequent illnesses
Work with school about special accommodations for physical limitations (physical education restrictions, mobility issues, flares)
Missed school time due to doctor’s appointments and surgeries
Stress/anxiety from looking different (clothing issues/compression garments)
Flares (bleeding, infection)
Watch for signs of scoliosis
Special accommodations at school
Missed school/work due to appointments and surgeries
Physical limitations
Stress from looking different, being stared at
Frequent illnesses
Special accommodations at school as developmental delays become more obvious
Missed school/work due to appointments and frequent illnesses
Physical and cognitive limitations
Stress on family unit, restrictions on activities
Children are often socially active, happy, but some may have behavioral disorders, such as autism or anxiety
Puberty/teenage years Hormonal changes with puberty can impact disease course
Developmental gap can widen
Pain and fatigue can become an increasing issue
Relationships with peers can change–bullying may occur and may start to deal with intimacy/sexual health issues
Anger and depression can emerge
Frequent illnesses
Hormonal changes with puberty can impact disease course, causing even “mild” cases to become more complex
Puberty brings an increase in clotting issues (DVT, PE, thrombophlebitis), as well as painful menstrual periods and/or weeping of lymphatic fluid that can cause stigma and shame
Flares also can become more frequent and pain can become worse
Watch for signs of scoliosis
Relationships with peers can change along with a period of anger because of stigma and limitations on activities
Teens start to deal with sexual health issues, including intimacy and birth control concerns
Hormonal changes with puberty can impact disease course
Gap in development can widen; less support provided at school
Pain and fatigue can become an increasing issue
Girls may have heavy, painful menstruation
Relationships with peers can change, bullying can occur and may start to deal with intimacy/sexual health issues
Frequent illnesses
Unable to participate in many activities
Hormonal changes with puberty can impact disease course
Developmental gap can widen
Special education services at school
May have difficulty with peers
Frequent illnesses, low energy
Young adulthood Move toward independent living
Transitioning to an adult care team
Struggle to educate themselves on their condition
Navigating intimate relationships and dealing with sexual health issues and genito-urological complications
Discussions on family planning
Patients with more severe physical/mental challenges remain at home and rely heavily on caregivers
Move toward independent living
Transitioning to an adult care team
Struggle to educate themselves on their condition
Patients with more severe physical challenges remain at home and rely heavily on caregivers
Continue dealing with sexual health issues, including birth control and genito-urological complications
Discussions on family planning
Move toward independent living
Transitioning to an adult care team
Taking responsibility for own care
Navigating intimate relationships and dealing with sexual health issues and genito-urological complications
Discussions on family planning
Patients with more severe physical/mental challenges remain at home and rely heavily on caregivers
Mildly affected patients may move toward independent living
Transitioning to an adult care team
May start to take responsibility for own care
Patients with more severe physical/mental challenges remain at home and rely heavily on caregivers
Parents may need to make decisions about guardianship
Older adulthood Increasing medical issues due to disease progression and comorbidities
Pain and fatigue leading to depression
Therapist/psychologist support
Potential disability, difficulty working full time
Increasing medical issues due to progression and comorbidities
Pain and fatigue leading to depression
Difficulty maintaining relationships
Inability to work full time due to fatigue, frequent infections, hospitalizations
Extensive planning needed for many activities
Increasing medical issues due to progression and comorbidities
Pain and fatigue leading to depression
Therapist/psychologist support
Potential disability, difficulty working full time
Reliance on mobility devices/support
Data were not available for this age group
  1. CLOVES, congenital lipomatous overgrowth, vascular malformations, epidermal nevi, scoliosis/skeletal and spinal anomalies; DVT, deep venous thrombosis; K–T, Klippel–Trénaunay; M-CM, megalencephaly-capillary malformation; PE, pulmonary embolism; PROS, PIK3CA-related overgrowth spectrum