CARING FOR THE CHILD WITH EHLERS-DANLOS SYNDROME Tamison Jewett, M.D. Associate Professor Department of Pediatrics Director, Clinical Genetics Services Wake Forest University Health Sciences Winston-Salem, NC

EDS Occurs in ~1/5000 individuals (all types combined)—much more common than once thought Occurs in ~1/5000 individuals (all types combined)—much more common than once thought Can be highly variable within families Can be highly variable within families Is diagnosed based on family history, symptoms, and physical exam findings Is diagnosed based on family history, symptoms, and physical exam findings Laboratory confirmation is available in the minority of cases Laboratory confirmation is available in the minority of cases

How is EDS inherited? Most forms are autosomal dominant Most forms are autosomal dominant Some forms are autosomal recessive Some forms are autosomal recessive

A quick genetics lesson…

Ideogram of the human chromosomes p-arm q-arm <= centromere autosomes Sex chromosomes NOR, ==> acrocentic <= Xp21

Autosomal dominant inheritance Dd x dd DdddDddd

Autosomal recessive inheritance Rr x Rr RRrRRrrr

A gene or genes may change for the first time in anyone. Therefore, a child with EDS may not have a parent with EDS.

When should the diagnosis of EDS be considered in a child? When there is/are: When there is/are: A positive family history of EDS in a first degree relative (mother, father, sister or brother) A positive family history of EDS in a first degree relative (mother, father, sister or brother) The classical triad of hyperextensible joints, hyperextensible skin, and poor wound healing The classical triad of hyperextensible joints, hyperextensible skin, and poor wound healing Hypotonia (sometimes severe) in an infant/child of otherwise unknown cause Hypotonia (sometimes severe) in an infant/child of otherwise unknown cause Recurrent joint dislocations Recurrent joint dislocations

When should the diagnosis of EDS be considered in a child? (cont.) When there is/are: When there is/are: Easy bruising Easy bruising Early onset and/or rapidly progressive scoliosis Early onset and/or rapidly progressive scoliosis Spontaneous pneumothorax Spontaneous pneumothorax Arterial rupture Arterial rupture Intestinal rupture Intestinal rupture Aortic root dilatation Aortic root dilatation

How do we define joint hypermobility? By using the Beighton criteria, as follows: By using the Beighton criteria, as follows: 1 point for passive dorsiflexion of each 5 th finger greater than 90 degrees 1 point for passive dorsiflexion of each 5 th finger greater than 90 degrees 1 point for apposition of each thumb to the flexor surface of the forearm 1 point for apposition of each thumb to the flexor surface of the forearm 1 point for hyperextension of each elbow greater than 10 degrees 1 point for hyperextension of each elbow greater than 10 degrees 1 point for hyperextension of each knee greater than 10 degrees 1 point for hyperextension of each knee greater than 10 degrees 1 point for the ability to place the palms on the floor with the knees fully extended 1 point for the ability to place the palms on the floor with the knees fully extended A score of 5/9 or greater is consistent with joint hypermobility.

Case 1: EDS, Classic Type Lilly is a 3 yo girl who has had multiple trips to the emergency department (ED) because of lacerations to her face, elbows, and knees after seemingly minor falls. The sutures often do not hold, and Lilly has taken longer to heal than expected. When she does heal, her scars are wide and thin. After one of her trips to the ED, her parents were reported to Social Services because Lilly had lots of bruises. Her parents say they don’t know what causes most of them. Lilly is a 3 yo girl who has had multiple trips to the emergency department (ED) because of lacerations to her face, elbows, and knees after seemingly minor falls. The sutures often do not hold, and Lilly has taken longer to heal than expected. When she does heal, her scars are wide and thin. After one of her trips to the ED, her parents were reported to Social Services because Lilly had lots of bruises. Her parents say they don’t know what causes most of them.

Case 1 (cont.) On examination, Lilly has: On examination, Lilly has: soft, velvety, hyperextensible skin soft, velvety, hyperextensible skin joint hypermobility (7/9 on the Beighton scale) joint hypermobility (7/9 on the Beighton scale) wide, paper-thin scars on her elbows and knees wide, paper-thin scars on her elbows and knees large bruises in various stages of healing over her shins large bruises in various stages of healing over her shins

Case 1 (cont.) Furthermore, Furthermore, Lilly was born prematurely at 30 weeks’ gestation after spontaneous rupture of membranes Lilly was born prematurely at 30 weeks’ gestation after spontaneous rupture of membranes Lilly sat, crawled, and walked later than expected Lilly sat, crawled, and walked later than expected Lilly’s dad has a similar medical history and physical findings Lilly’s dad has a similar medical history and physical findings There is no abnormality of collagen found in Lilly’s cultured skin cells There is no abnormality of collagen found in Lilly’s cultured skin cells

Management of the Child with EDS, Classic Type MedicAlert tag MedicAlert tag Pads/bandages over sites of frequent trauma Pads/bandages over sites of frequent trauma Wounds requiring stitches can be closed in 2 layers and with the help of steri-strips or tape; consider leaving stitches in place longer Wounds requiring stitches can be closed in 2 layers and with the help of steri-strips or tape; consider leaving stitches in place longer Local anesthetics may not be very effective; consider waiting a longer time after administration to do procedure Local anesthetics may not be very effective; consider waiting a longer time after administration to do procedure Consult with Plastic Surgery for repair of facial wounds Consult with Plastic Surgery for repair of facial wounds Physical therapy to improve muscle strength Physical therapy to improve muscle strength

Management (cont.) Avoidance of heavy lifting Avoidance of heavy lifting Avoidance of contact sports Avoidance of contact sports Echocardiogram(s) to look for “floppy” valve(s) and/or aortic root dilatation Echocardiogram(s) to look for “floppy” valve(s) and/or aortic root dilatation Anticipatory guidance regarding potential pregnancy complications, surgical complications, pain management, psychological implications Anticipatory guidance regarding potential pregnancy complications, surgical complications, pain management, psychological implications Vitamin C supplementation Vitamin C supplementation

Case 2: EDS, Hypermobility Type Jordan is a 5 yo boy who was noted on his pre- kindergarten physical exam to be unusually “double-jointed.” His parents say that he is generally healthy, but he has had nursemaid’s elbow repeatedly, and he can “pop” his shoulders out of joint at will. When asked, Jordan shows you his entire repertoire of stunts, which includes stepping through his clasped hands and bringing them all the way around his back and over his head without un-clasping them.

Case 2 (cont.) On examination, Jordan has On examination, Jordan has joint hypermobility (9/9 on the Beighton scale) joint hypermobility (9/9 on the Beighton scale) soft, mildly hyperextensible skin soft, mildly hyperextensible skin normal scar formation normal scar formation

Case 2 (cont.) Furthermore, Furthermore, Jordan’s mother and maternal grandfather have a history of frequent joint dislocations throughout childhood and adulthood and now suffer from multiple painful joints Jordan’s mother and maternal grandfather have a history of frequent joint dislocations throughout childhood and adulthood and now suffer from multiple painful joints There is no abnormality of collagen found in Jordan’s cultured skin cells There is no abnormality of collagen found in Jordan’s cultured skin cells

Management of the Child with EDS, Hypermobility Type MedicAlert tag MedicAlert tag Avoidance of activities that promote dislocation Avoidance of activities that promote dislocation Avoidance of heavy lifting Avoidance of heavy lifting Physical/occupational therapies to promote strengthening of muscles and improve fine motor skills; non-weight-bearing exercises and hydrotherapy Physical/occupational therapies to promote strengthening of muscles and improve fine motor skills; non-weight-bearing exercises and hydrotherapy Pain management (pain is a major complication of this type of EDS) Pain management (pain is a major complication of this type of EDS) Psychological intervention as needed Psychological intervention as needed Echocardiogram(s) Echocardiogram(s) Vitamin C supplementation Vitamin C supplementation

Case 3: EDS, Vascular Fragility Type Ellie is a 7 yo girl who was born with a clubfoot. When Ellie was 2 yo, her mom noticed a lump in Ellie’s groin while changing her diaper, and she was diagnosed with a hernia, which required surgical repair. Ellie has a history of frequent, easy bruising. She has very flexible fingers, and she receives occupational therapy in school due to difficulty with writing, buttoning her shirts, and snapping her pants.

Case 3 (cont.) On examination, Ellie has On examination, Ellie has a round face, delicate nose, and prominent eyes a round face, delicate nose, and prominent eyes translucent skin with easily visualized veins, especially on the trunk translucent skin with easily visualized veins, especially on the trunk delicate fingers that are markedly hypermobile delicate fingers that are markedly hypermobile multiple bruises, in various stages of healing, on the arms and legs multiple bruises, in various stages of healing, on the arms and legs

Case 3 (cont.) Furthermore, Furthermore, Ellie’s maternal grandmother died at age 27 from complications of an arterial aneurysm Ellie’s maternal grandmother died at age 27 from complications of an arterial aneurysm Ellie’s mother has similar physical features to Ellie and has a history of intestinal rupture Ellie’s mother has similar physical features to Ellie and has a history of intestinal rupture Ellie has laboratory findings consistent with EDS, Vascular Fragility Type, in cultured skin cells Ellie has laboratory findings consistent with EDS, Vascular Fragility Type, in cultured skin cells

Management of the Child with EDS, Vascular Fragility Type MedicAlert tag MedicAlert tag Avoidance of contact sports, heavy lifting Avoidance of contact sports, heavy lifting Careful attention to complaints of headache, chest pain, abdominal pain Careful attention to complaints of headache, chest pain, abdominal pain Physical/occupational therapy as needed Physical/occupational therapy as needed Psychological intervention as needed Psychological intervention as needed Echocardiogram(s) Echocardiogram(s) Anticipatory guidance for surgery, pregnancy/conservative management of vascular complications Anticipatory guidance for surgery, pregnancy/conservative management of vascular complications

Case 4: EDS, Kyphoscoliotic Type Sam is a 10 yo boy with severe scoliosis that has required surgical intervention. His scoliosis was first noticed when he was a toddler, and his orthopedist thinks it was probably present at birth. As a baby, Sam was very hypotonic; he sat alone at 10 months and walked at 2 years. Sam has had recurrent nursemaid’s elbow, and recently, he dislocated his knee when walking down stairs. He wears glasses for nearsightedness, which has progressed rapidly.

Case 4 (cont.) On examination, Sam has On examination, Sam has A slender build A slender build Joint hypermobility (8/9 on the Beighton scale) Joint hypermobility (8/9 on the Beighton scale) Soft, stretchy skin Soft, stretchy skin Evidence for scoliosis repair with some scoliosis remaining Evidence for scoliosis repair with some scoliosis remaining Widened, paper-like scars Widened, paper-like scars Thick glasses Thick glasses

Case 4 (cont.) Furthermore, Sam has Furthermore, Sam has no family history of similar features no family history of similar features lysyl hydroxylase deficiency on biochemical testing of cultured skin cells lysyl hydroxylase deficiency on biochemical testing of cultured skin cells a mildly dilated aortic root detected by echocardiogram a mildly dilated aortic root detected by echocardiogram

Management of the Child with EDS, Kyphoscoliosis Type MedicAlert tag MedicAlert tag Early identification of scoliosis with close monitoring by an orthopedist Early identification of scoliosis with close monitoring by an orthopedist Regular ophthalmologic exams Regular ophthalmologic exams Avoidance of heavy lifting/contact sports Avoidance of heavy lifting/contact sports Physical/occupational therapy beginning in infancy Physical/occupational therapy beginning in infancy Echocardiogram(s) Echocardiogram(s) Vitamin C supplementation Vitamin C supplementation Maintaining good fluid intake Maintaining good fluid intake Psychological intervention as needed Psychological intervention as needed

Case 5: EDS, Arthrochalasia Type Anna is a 6 yo girl who was born with bilateral hip dislocation. Despite surgical repair of her hips, she continues to have pain in her hips and has an unusual gait. Her orthopedist says she will need further hip surgery. She is “double- jointed” and has had multiple joint dislocations. Recently, she was diagnosed with scoliosis.

Case 5 (cont.) On examination, Anna has On examination, Anna has hypermobile joints with painful, and reduced, range of motion of the hips hypermobile joints with painful, and reduced, range of motion of the hips mildly stretchy skin with some widened scars mildly stretchy skin with some widened scars scoliosis scoliosis

Case 5 (cont.) Furthermore, Anna has Furthermore, Anna has no family history of similar features no family history of similar features an abnormality of collagen detected on biochemical analysis of cultured skin cells consistent with EDS, arthrochalasia type an abnormality of collagen detected on biochemical analysis of cultured skin cells consistent with EDS, arthrochalasia type

Management of the Child with EDS, Arthrochalasia Type MedicAlert tag MedicAlert tag Ongoing orthopedic management Ongoing orthopedic management Physical therapy as needed Physical therapy as needed Avoidance of heavy lifting/contact sports Avoidance of heavy lifting/contact sports Pain management Pain management Psychological intervention as needed Psychological intervention as needed Echocardiogram(s)? Echocardiogram(s)? Vitamin C supplementation Vitamin C supplementation

Adjustments in the Home for Children with EDS Avoid rugs that can slip Avoid rugs that can slip Minimize sharp corners on furniture, hearth, etc. Minimize sharp corners on furniture, hearth, etc. Padded furniture may be preferable to wooden or metal furniture Padded furniture may be preferable to wooden or metal furniture A ranch-style house may be preferred if stairs are difficult A ranch-style house may be preferred if stairs are difficult Teach children to pick up toys and minimize rough-housing (haha!) Teach children to pick up toys and minimize rough-housing (haha!)

Adjustments at School for Children with EDS Discuss, as you feel appropriate, your child’s diagnosis with the principal/teachers (you may wish to provide literature) Discuss, as you feel appropriate, your child’s diagnosis with the principal/teachers (you may wish to provide literature) Ask that physical activity be closely monitored and that accidents/injuries be promptly reported Ask that physical activity be closely monitored and that accidents/injuries be promptly reported Create a plan in case of injury Create a plan in case of injury Ask that physical activity be limited as recommended for your child’s diagnosis, and provide documentation as necessary Ask that physical activity be limited as recommended for your child’s diagnosis, and provide documentation as necessary

Adjustments at School (cont.) Children who must carry books to/around school should be allowed to have a rolling backpack and/or a separate set of books for school and home Children who must carry books to/around school should be allowed to have a rolling backpack and/or a separate set of books for school and home Have your child evaluated for physical/occupational therapy needs while at school Have your child evaluated for physical/occupational therapy needs while at school Modifications should be made to desks, chairs, writing instruments, etc. as needed Modifications should be made to desks, chairs, writing instruments, etc. as needed Most children with EDS do not have learning difficulties, but if there is a learning concern, this should be appropriately addressed Most children with EDS do not have learning difficulties, but if there is a learning concern, this should be appropriately addressed

Friends of the Child with EDS Don’t need to know everything but do need to know “activity rules” and to report serious injury Don’t need to know everything but do need to know “activity rules” and to report serious injury Are likely to ask questions; answer them simply Are likely to ask questions; answer them simply SHOULD BE ENCOURAGED AND NURTURED; normalcy is important SHOULD BE ENCOURAGED AND NURTURED; normalcy is important

Who Manages the Child with EDS? Pediatrician Pediatrician Orthopedist Orthopedist Physical and/or occupational therapist Physical and/or occupational therapist Dentist Dentist Pediatric surgeon Pediatric surgeon Dermatologist Dermatologist Plastic surgeon Plastic surgeon Geneticist/genetic counselor Geneticist/genetic counselor Nutritionist Nutritionist

Who Manages? (cont.) Ophthalmologist Ophthalmologist Vascular surgeon Vascular surgeon Pediatric cardiologist Pediatric cardiologist Psychologist/psychiatrist Psychologist/psychiatrist Gynecologist Gynecologist Obstetrician Obstetrician Pain management specialist Pain management specialist Pediatric rheumatologist Pediatric rheumatologist

Children with EDS are children first. Like all children, they should be given every opportunity to reach their full potential and to safely experience what life has to offer.