Medical Management of SRS

For SRS Families & Friends:

The following document, called the Medical Management of SRS, contains information collected by SRS patient records from the Natural History Study (NHS) and can be brought to your loved ones’ doctors for their consideration & better understanding of possible medical issues associated with SRS. It is not medical advice, but rather an ongoing list of all the medical findings in the SRS population, as reported by the SRS families enrolled in the Natural History Study. This list will be updated as more patient information is received. If you are an SRS family who has not yet taken part in the Natural History Study, please contact us today. You have information about your loved one’s condition that will help our data and better our understanding of SRS as a whole.

We now offer the SRS Medical Management document in 12 languages: Dutch, English, French, German, Greek, Hungarian, Italian, Japanese, Norwegian, Polish, Portuguese, and Spanish for our SRS families around the world.

DUTCH

MEDISCH BEHEER VAN SRS IN HET NEDERLANDS

LEZEN
ENGLISH

MEDICAL MANAGEMENT OF SRS IN ENGLISH

VIEW PDF
FRENCH

SOINS MEDICAUX DES SRS EN FRANCAIS

LIRE
GERMAN

MEDIZINISCHES VERWALTUNG VON SRS AUF DEUTSCH

LESEN
GREEK

IATPIKH ΔIAXEIPIΣH SRS ΣTA EΛΛHIKA

ΑΝΑΓΝΩΣΗ
HUNGARIAN

AZ SRS ORVOSI IRÁNVITÁSA MAGYARUL

OLVAS

ITALIAN

GESTIONE MEDICA DI SRS IN ITALIANO

LEGGERE
JAPANESE

SRS の医療管理

読む
NORWEGIAN

MEDISINSK FORVALTNING AV SRS I NORSK

LESE
POLISH

OPIEKA MEDYCZNA DLA SRS PO POLSKU

CZYTAĆ
PORTUGUESE

GESTÃO MÉDICA DE SRS EM PORTUGUÊS

LER
SPANISH

MANEJO MÉDICO SRS EN ESPAÑOL

LEER

MEDICAL MANAGEMENT OF SRS IN ENGLISH (link to PDF version above)

THIS WEBSITE DOES NOT PROVIDE MEDICAL ADVICE: The content of this document is for informational purposes only. It is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and should not be used as a medical standard of care.

A NOTE TO HEALTH CARE PROVIDERS: Snyder-Robinson Syndrome (SRS) is an ultra-rare disorder. At the time of this writing, we are aware of fewer than one hundred cases worldwide. Consequently, the existing medical literature provides a limited description of the disorder. We hope the information on this page will enable providers to consider some helpful work-ups and evaluations that might not otherwise have been apparent, based on a review of SRS patient records in our Natural History Study. Considerations for these suggested work-ups are not exhaustive, and we welcome feedback from providers.

If your SRS patient is currently enrolled in our Natural History Study, please discuss submitting ongoing medical data to the Natural History Study. This will help to expand the information for other physicians, researchers, and other SRS patients–even routine care may help indicate a trend.

If your SRS patient is NOT currently enrolled in the Natural History Study, please encourage them to help others by sharing their medical data. Their request to participate may be made by clicking here.

Thank you for your care of our SRS family members and your contributions to the SRS community!

For Health Care Providers:

The purpose of this document is to aid physicians and other health care providers in the day-to-day management of the complex medical issues which arise in patients who have Snyder-Robinson Syndrome (SRS). We are also asking the medical community to help gather more data. This data will contribute to an expansion of the SRS phenotype, which has considerable variability.

Snyder-Robinson Syndrome has been reported in the literature and noted by clinical experts to exhibit various clinical findings, which can be referenced in the updated GeneReviews: Schwartz CE, Peron A, Kutler MJ. Snyder-Robinson Syndrome. 2013 Jun 27 [Updated 2020 Feb 13]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020. Available from: www.ncbi.nlm.nih.gov/books/NBK144284/

Below, you will find a list of observational findings which have been reported in the SRS population. These observations are designed for consideration purposes and are listed with a ‘systems’ approach. Some of these findings have unclear clinical significance but have been reported by families and/or reported by clinicians. Many of these findings are discussed in the above mentioned GeneReviews article. Additional considerations are mentioned here to aid clinicians in their evaluation and treatment of the SRS patient, giving attention to further details which may be less commonly observed. In rare disorders, it is often helpful for families and health care providers to be aware of what has been reported even anecdotally to provide some guidance for care and potentially some reassurance.

General Systems Review:

Constitutional – Monitor weight, length, height and head circumference. SRS patients have an asthenic body habitus (thin, slender build) and many have a history of failure to thrive requiring intervention. Some patients have macrocephaly. Currently there is not a growth chart specific to the SRS patient. Developmental assessment should include motor, adaptive, cognitive, and speech/language milestones. Evaluation for early intervention/special education is recommended.

Sleep – There have been reports of abnormal sleep patterns in patients with SRS. These reports are varying and non-specific in nature; the significance is not known at this time, and it is mentioned here for informational purposes. It is recommended to document any sleep abnormalities in the medical record for trending purposes to help determine the nature of this symptom.

Pain – Parents of SRS patients have reported concerns for their child having ‘pain’; to date, the etiology is unclear. Often these pain episodes are intermittent but significant enough to warrant medical evaluations. These events have been worked up by the primary care physician without a specific cause identified. It would be helpful for these patients to seek medical attention when pain episodes occur. Caretakers should document/journal the nature of complaints, the quality of the pain, time/duration of the pain, and what alleviates or aggravates the pain. The clinician should use a systematic approach for evaluation.

Sweating – Hypo- or hyperhidrosis, when present, appears to be an incidental complaint which is currently being followed for its significance. It is mentioned here because hyperhidrosis, when present, can be varied in nature. Screening studies should be considered to rule out other medical conditions such as hypoglycemia, thyroid disease and other hormonal imbalances. Recommendations are to clinically evaluate, document and track when present.

Neurology

Ophthalmology

Brain dysfunction must be evaluated to rule out cortical visual impairment in SRS patients who may have visual problems which are not specifically attributed to the physiology of the ocular structures, refraction or abnormal eye movement.

Cortical Vision Impairment (CVI) – At this time, a few patients have been reported to have CVI. It is unclear if this is a statistically significant SRS characteristic, but it is mentioned here for the purposes of discussion in order to encourage providers to seek further ophthalmologic evaluation when medically indicated. Pediatric neurology as well as pediatric ophthalmology exams should be considered to evaluate any acquired visual impairment.

Some common presenting symptoms of CVI include: inability to follow, focus or track, which may be intermittent in nature, photophobia, inconsistent visual responses with an avoidant social gaze or a gaze which appears to be blunted. These patients may or may not have poor visual acuity. The behaviors are varied and there are inconsistencies in visual responses to similar stimuli. They typically have fatigue from visual tasks and may have difficulty seeing objects in a busy background.

Myopia – It appears that myopia may be an ophthalmologic finding in SRS patients. It would be recommended that SRS patients are screened yearly for this concern.

Of note, other findings/complaints which have been recorded include: crowded drusen, pale optic nerve, torpedo shaped retinal lesion, pigmented retina, eye pain and photophobia; however, significance to SRS patients is unclear at this time.

ENT

Abnormal palate morphology – cleft/narrow/high arched palate and/or bifid uvula has been reported. Clinical evaluation including feeding assessment should be done when indicated.

Hearing

Hearing impairment – Some SRS patients have sensorineural and/or conductive hearing impairment significant enough to require hearing aids. A few SRS patients have hearing loss, which has been reported to be progressive. These patients are being followed. Yearly audiology evaluation should be performed. Despite the appearance of a generally normal evaluation, it would be beneficial to have the audiologist compare the waveforms to the previous exam to determine if there are subtle changes. It would also be valuable to track this over time to determine if hearing loss is progressive in the SRS patient.

Dental

Abnormal dental morphology – Various presentations of dental issues have been documented in SRS patients. These include overcrowded teeth, caries, blackened teeth, enamel hypoplasia and abnormal or peg-shaped teeth. Dental exams by a pediatric dentist are recommended every 6 months at eruption of the first tooth or 12 months of age.

Pulmonology

Reactive Airways Disease – Patients with SRS may have a history of asthma or episodic asthma, but also may present with respiratory distress of unclear etiology, which requires a bronchodilator and/or supplemental oxygen. An interesting clinical presentation in some SRS patients is that they may have an abundance of respiratory/mucous secretions, which are quite thick in nature. This finding does not have statistical significance at this time but needs to be followed closely due to the dramatic viscosity in presentation. A few patients have significant respiratory compromise and/or apnea, which require additional support with CPAP/BiPAP. Some patients require a tracheostomy. Treatment regimens are varied and include oral steroids, nebulized treatments with bronchodilators, hypertonic saline, acetylcysteine, and/or inhaled corticosteroids. Some patients also receive airway clearance via suctioning, chest physiotherapy and/or supplemental oxygen when clinically indicated. Any SRS patient who has multiple episodes of reactive airways requiring bronchodilator or oral steroid therapy should be evaluated by a pulmonologist. In addition, those patients with recurrent respiratory infections should be assessed by pulmonology as well as immunology. (See immunology comments below).

Cardiology

Abnormal heart morphology – A few SRS patients have been reported to have various congenital structural heart abnormalities. It is unclear as to the statistical significance in comparison to the general population, but echocardiogram should be considered in SRS patients when medically indicated.

Gastroenterology

Failure to Thrive – Many SRS patients have a diagnosis of failure to thrive for various reasons. Any patient who is not meeting appropriate growth parameters should be evaluated and tracked. Currently, there is not a growth chart developed specifically for SRS patients. This should be taken into consideration when tracking growth on standard growth charts.

Feeding issues – Many SRS patients have feeding issues requiring intervention including GT/GJ tube placement or TPN.

Constipation – Chronic constipation is a finding in most SRS patients. This does not appear to be related to immobility; patients who are both ambulatory as well as non-ambulatory suffer with chronic constipation. Most of these patients are managed with polyethylene glycol.

Findings of unknown/unclear statistical significance include: Diarrhea, gastrointestinal inflammation, gastroesophageal reflux disease, vomiting and elevated hepatic transaminases.

Diarrhea – Some SRS patients have intermittent diarrhea, which may contain blood or mucous.
Gastrointestinal inflammation such as Crohn’s, colitis and gastritis – Varied presentations of gastrointestinal inflammation are noted in some SRS individuals. (Statistical significance is unknown at this time).
Gastroesophageal Reflux Disease/Vomiting – GERD is another gastrointestinal presentation of unclear statistical significance at this time. Clinical evaluation and treatment would be warranted.
Elevated hepatic transaminases (intermittent in nature) – This finding has been noted in a few SRS patients, some of which are severe. It is mentioned here because of its intermittent nature and the need to follow liver studies closely over time.

Despite the unclear statistical significance of the varied gastrointestinal presentations in SRS patients, a baseline formal evaluation by a gastrointestinal physician is recommended. It is also suggested to consider following liver function studies at routine intervals and during illnesses as medically indicated.

Urology

Urine with whitish powder or sediment – There have been some reports of SRS patients who have an unknown whitish powder or sediment in their urine, which has been noted as a prominent debris/layering in the bladder on ultrasound reports. (See nephrology comments below). At this time, the etiology of this powder is unclear. Samples have been reported as calcium phosphate (apatite) also known as carbonate apatite. Due to the dramatic presentation of this sediment in a few patients, it is mentioned here for informational purposes. Routine microscopic urine analysis is recommended during well visits and should be considered at sick visits. A urology referral is recommended to work up this sediment when medically indicated.

Nephrology

Nephrolithiasis has been reported in some SRS patients. A screening renal ultrasound should be considered and repeated periodically to document the presence or absence of kidney stones and/or structural abnormalities. Tubulopathy has been documented in at least 3 patients. Additionally, as stated above, debris in the bladder, as well as urinary sediment consisting of calcium phosphate/carbonate apatite has been reported.

Creatinine level as it relates to kidney disease – It is recommended to monitor the serum creatinine in SRS patients, as they typically have low muscle mass. It is not uncommon for SRS patients to have a low creatinine at baseline due to this decreased muscle mass. A creatinine result listed as normal by standard laboratory parameters may be falsely reassuring when in fact that level may actually be elevated relative to the low muscle mass. This could be an important indication of renal disease. When following creatinine levels, compare and trend changes from the patient’s baseline.

Hematology

Anemia – Iron deficiency anemia has been noted in some SRS patients, but it may not be statistically significant when compared to the general population. Consider screening labs for anemia.

Thrombocytopenia – Episodes of neonatal thrombocytopenia have been documented. Currently there is not a recommendation to check platelets at birth as a screening lab. If a patient is born with a diagnosis of SRS which was determined antenatally (due to prior knowledge of SRS family history), consideration for following platelet trends at birth would be valuable. Some SRS patients have had intermittent thrombocytopenia of unclear significance. Consider the trending of routine complete blood counts as medically indicated.

Endocrinology

Osteoporosis – Nearly all SRS patients have early onset osteoporosis and fractures in the absence of trauma. It is recommended that the clinician obtain bone mineral density studies/DEXA scans early and follow for evidence of osteopenia or osteoporosis. Several individuals are on calcium supplementation and/or treated with bisphosphonates. If a patient is receiving bisphosphonates, it is recommended to follow serial bone mineral density studies/DEXA scans to evaluate efficacy. The overall effectiveness is being trended.

Hypoglycemia – Some patients have neonatal hypoglycemia, and it has been noted that hypoglycemia is an intermittent finding of unclear significance in the SRS population. Consideration should be given to follow chemistry panels routinely and/or during illness when medically appropriate.

Hyperglycemia – Hyperglycemia is another finding noted in the SRS population. This can be tracked in a patient when chemistry panels are obtained.

Immunology

There may be a possible immune component to SRS. Multiple types of infections are noted, which include frequent episodes of otitis media (requiring PE tubes), sinusitis, upper respiratory infections, pneumonia and urinary tract infections. There has been documentation of abnormal immunoglobulins in a few patients and, in some cases, immunoglobulin therapy (IVIG or SCIG) is administered as treatment. Several patients have had recurrent, intermittent, and unexplained fevers. Some treating physicians of these patients have suggested immune dysregulation and/or an autoimmune component and treatment on at least one patient includes immunosuppressants. Given the unpredictability of immunologic findings, an immune evaluation may be helpful in establishing a baseline and/or in identifying potential immunologic causes of a patient’s symptoms.

The following table includes clinical tests which are typically used by immunologists to evaluate immune function.

Orthopedic/Musculoskeletal

Along with osteoporosis, SRS patients have both scoliosis and kyphoscoliosis. Imaging studies should be obtained and followed yearly at the first sign of scoliosis. Abnormal pectus has also been noted.

Ulnar deviation, genu valgum, and other joint mobility abnormalities (joint laxity/contractures/joint subluxation) have also been observed. Appropriate referrals for orthopedics, physical therapy, occupation therapy and physiatry are recommended when indicated.

Psychiatry/Developmental Pediatrics

When clinically appropriate, evaluation with psychiatry and/or developmental pediatrics should be considered. We are currently tracking reports of autism and/or sensory issues. It would be recommended to obtain psychiatry/developmental pediatric evaluations when clinically indicated.

Genetics

Counseling with a geneticist and/or genetic counselor is advised.

Mary Jo Kutler, DO

Principal Investigator, Global Snyder-Robinson Syndrome Registry & Natural History Study

Contact: maryjo.kutler@snyder-robinson.org.

Updated 3/22/2023