Sample information letter

                                                  
Medical Genetics
                                                                                                    May 14, 2020
Doctors
 

                                                                                     RE: Jane Doe  BD: 1-1-1981
Dear Doctor:
 
I offered to review the history and physical findings of Ms. Jane Doe on July 14, 2020 as she requested after becoming concerned about symptoms of Ehlers-Danlos syndrome (EDS). I would emphasize that this review is for information only and cannot be taken as a medical diagnosis. I perform this information service as part of my ongoing clinical scholarship on EDS that aims at better recognition of this complex disorder. I hope that Ms. Doe and her physicians will become more informed about EDS from this letter and its attachments, that they will help her primary care and subspecialty physicians consider EDS and its many complications in their management plans.
        IMPRESSION: My overall impression is that the findings listed by Ms. Doe using my standard forms fit the pattern of arthritis-adrenaline disorder (AAD)* as a category and Ehlers-Danlos syndrome (EDS—classical type) as a particular condition based on my prior 1900+ EDS evaluations. She is 35 years old and reports 40 of 80 typical findings by history (higher than 70% of my female EDS patients of that age) and 18 of 40 on physical (higher than 60% of my female EDS patients).* These findings include joint hypermobility with subluxations and joint-muscle pain, skin fragility, pelvic pooling/menorrhagia, headaches and other neuromuscular symptoms, and the dysautonomia that can lead to irritable bowel syndrome (IBS), postural orthostatic tachycardia syndrome (POTS), and mast cell activation disorder (MCAD)—see her entries on the attached standard forms to appreciate all of her findings. My impression suggests that she has a medical disorder that can cause anxiety from POTS and depression from pain and activity limitation rather than a psychiatric disorder or hypochondriasis.
I encourage her to follow through with her physicians and consider the attached nutritional and joint protection strategies as modified by their diagnoses. If she and her physicians agree with my impression that her findings fit with a form of EDS, then their opinion supplemented by this information constitutes a clinical diagnosis of EDS and dysautonomia, a category that I call arthritis-adrenaline disorder (AAD) that encompasses EDS and related disorders.
Because many patients with EDS are concerned about severe types like vascular EDS, they may want to exclude this possibility by DNA testing. While extremely unlikely, severe types affecting at most 2 of my 1900+ EDS patients, the most economical and efficient way to exclude them is an EDS panel through the Invitae Company (www.invitae.com, self-pay $250 but often at least partially covered by insurance). I no longer have the resources to coordinate such testing but a patient or any of their doctors can order it (patient orders can incur an additional ~$100 counseling fee from Invitae). Another option is whole exome sequencing that screens all 23,000+ genes through Invitae, GeneDx, and others (costs $1200-$2500 and decreasing; see the information on DNA testing that accompanies this letter). Exome sequencing can include looking at other harmful genes like those for breast-ovarian or colon cancers with the patient’s consent. I am happy to review any DNA testing results obtained as part of this information service and my ongoing scholarship.
 
PAST MEDICAL HISTORY: Brief review of the natural history (see natural and family history form) indicates that Ms. Doe reports major concerns of joint and muscle pain suggestive of early arthritis, unexplained tachycardia, and spinal disc issues.  More severe symptoms began at age 10 with muscle sprains and worsened from ages 15 to 30 as shown on the natural and family history form. Significant among the 40 of 80 characteristic history findings she reports (see history form) are infantile colic that can be an early sign of IBS, early awareness of hypermobility with pain in several joints, easy bruising and scarring of her skin, and menorrhagia with bladder issues that often occur in EDS. Neuromuscular complaints include migraines, numbness and tingling, muscle aches involving her lower legs. She has many dysautonomia findings including constipation/diarrhea, bloating/reflux/stomach pain of IBS, chronic fatigue and tachycardia among many symptoms of POTS, transient rashes, asthma/shortness of breath, and food-medication intolerances suggestive of MCAD. Laboratory studies have included the low vitamin D levels often seen with EDS.
 
FAMILY HISTORY: Her family history form lists the following individuals with some symptoms of EDS-dysautonomia including one of two siblings, her mother, her father with only joint laxity and injuries, her maternal grandmother, and her paternal grandmother.
 
PHYSICAL EXAMINATION: Significant among the 18 of 40 typical physical findings of EDS reported by Ms. Doe are tall stature (70 inches or at the 97th centile for adult females) and long fingers with ability to perform the Walker-Murdoch sign (see physical exam form). She describes presence of a forward neck curve with lordosis; soft and lucent skin with many unusual scars, and dramatic hypermobility with a Beighton score of 8/9. She indicates ability able to do other hypermobility maneuvers like joining hands one over shoulder/one around back and the prayer sign behind her back, reporting difficulty with balance when doing the tandem walk maneuver.
 
IMPRESSION: My impression is that the findings reported by Ms. Doe are consistent with a moderate form of Ehlers-Danlos syndrome (EDS), her hypermobility and skin findings with scarring being most typical of the classical cEDS type. She did report headaches that can indicate increased intracranial hypertension/Chiari deformation or cranio-cervical instability that are more common in EDS-- she may wish to have upright MRI studies with neck flexion/extension to exclude these complications. In her 35 years Ms. Doe has not developed the facial changes, the bowel/blood vessel/uterine ruptures, or the lethal complications during    pregnancies that can be seen in vascular and other severe forms of EDS.
While severe EDS types must be definitively excluded by DNA testing, cardiovascular screening for aneurysms could exclude these risks and may be better covered by insurance than DNA testing that is often viewed as experimental. This uneducated view and my mentioned lack of staff are two reasons I stopped coordinating DNA testing, but third and most important is the fact that clinical and not DNA findings in 800+ tested patients guided management.  I do feel that screening all genes is valuable for everyone and that its discovery of new genes causing EDS will eventually merit insurance coverage. I will be happy to interpret DNA results as part of this service for patients who can arrange testing for reasonable costs (under $300 in my opinion--see information on EDS therapy and how gene discoveries will provide future insights and strategies).   
I feel that common forms of EDS belong to an arthritis-adrenaline disorder (AAD) category that involves a central process of articulo-autonomic dysplasia with reciprocal articular laxity and dysautonomia as diagrammed in the attachment. Tissue laxity/lower body blood pooling stimulates adrenaline to restore brain circulation with one stroke, the autonomic imbalance producing small fiber neuropathy and weak muscle fibers to increase tissue laxity with the other. This cycle implies universal therapies for EDS and related disorders that include 1) joint protection, physical therapy, and exercise strategies to build core strength/muscle protection that will constrain hypermobility and joint instability; 2) hydration, vitamin supplement, lower gluten-lactose and other nutritional strategies to curb fight-or-flight adrenergic stimulation; and 3) medication therapies coordinated by subspecialists who are familiar with these skeletal and autonomic complications (see attached therapy information).
Ms. Doe may have inherited her connective tissue flexibility from both her mother and father’s side with her siblings, mother, father, and grandmothers having EDS symptoms. The milder, more common forms of EDS can arise from many genes and are always modified by environmental factors, a mechanism known as multifactorial determination. Affected individuals have increased risk to transmit their susceptibility to offspring, varying from the 50% implied by a single, dominant-acting gene mutation to the 3-5% for each pregnancy based on multifactorial determination. Additional benefits of DNA testing are to refine these recurrence risks in Ms. Doe and her relatives and to provide additional evidence for an EDS diagnosis.
 
RECOMMENDATIONS: I would like Ms. Doe to use information in this letter and attachments to inform her own conclusions about an EDS-dysautonomia diagnosis, contacting the appropriate physicians to make formal medical diagnoses if she and they think they are justified. I encourage Ms. Doe to join me in spreading information about EDS to patients and physicians and to contact me (email best) with other questions or concerns.
 
Sincerely yours
  
Golder N. Wilson MD, PhD
Certified in Pediatrics & Medical Genetics
 
cc:
Ms. Jane Doe by email