Handbook of Genetic Counseling/Stickler Syndrome

Stickler Syndrome Introductions Contracting What is your understanding of why your doctor referred you to see us? Do you have any questions or concerns? You are probably already familiar with Stickler syndrome since you have it yourself, but your doctor probably just wanted to make sure you understand the chance for your child to have it as well as the potential for a child to have different characteristics or symptoms than you. We also may have the ability to do prenatal testing to see if your fetus has Stickler syndrome. Is this something you are interested in? Establish an agenda: Obtain medical and family history to determine if there are any other risks that we might want to talk about, answer any questions you might have about Stickler syndrome, discuss risks Elicit Family History Are there any other members of the family who have a diagnosis if Stickler syndrome Any family members with cleft palate, recurrent ear infections, nearsightedness, blindness, cataracts, glaucoma, astigmatism, early-onset arthritis, hyperextendable joints, joint replacements in the 30-40s, joint stiffness, hearing impairment (high-tone?), mitral valve prolapse, or a flattened midface Anyone die young or unexpectedly Anyone with Mental retardation/learning difficulties Birth defects (heart defects, CL/CP, spina bifida) Chronic illnesses such as diabetes or heart disease Anyone with cancer diagnosed at a young age (before 50) Stickler Syndrome (a.k.a. hereditary artho-ophthalmopathy) A connective tissue disorder that can affect the ocular (eyes), craniofacial (formation of facial structures), audiologic (hearing), cardiovascular (heart), and skeletal systems. Connective tissue (CT) is the most plentiful protein in the body and acts as support tissue. CT can allow for elastic stretching and tightening, especially in the muscles. Prevalence: 1/7500 - 1/10,000 - often goes undiagnosed in individuals with mild symptoms Affects both sexes Clinical Description Symptoms vary from patient to patient, even within the same family) Patients do not usually have all the symptoms!! Features include: Ophthalmologic Congenital or early-onset cataracts. Myopia (non-progressive, detectable in newborn period) - can lead to retinal detachment, which can result in blindness. Glaucoma Vitreal anomalies (gel that fills the eye). Type 1 characterized by a persistence of a vestigial vitreous gel in the retrolental space and is bordered by a folded membrane, present at birth. Type 2 is much less common, and is characterized by sparse and irregularly thickened bundles throughout the vitreous cavity, have milder ocular findings. Types of vitreal fluid anomalies breed true within families. Craniofacial Midface hypoplasia Depressed nasal bridge (in childhood) Anteverted nares (upturned nose) Bifid uvula, submucous cleft, or cleft palate Robin sequence (micrognathia, cleft palate, and glossoptosis) Audiologic Hearing impairment (40%) - degree of impairment (typically high one) is variable and may be progressive. Sensorineural hearing loss (common) Conductive hearing loss can also be seen. Skeletal (problems tend to worsen with age) Short stature as compared to unaffected siblings Marfanoid body habitus without tall stature Hypermobility Joint laxity (becomes less prominent with age) Mild spondyloepiphyseal dysplasia Precocious osteoarthritis - joint pain in childhood may signify the onset, can be a major complication in adulthood. Scoliosis Mitral Valve Prolapse (45-50%) - occurs when the heart valve shuts and then protrudes into the next chamber. Possible learning difficulties due to sight and hearing problems/ Diagnosis Clinical diagnosis At present, no consensus minimal clinical diagnostic criteria exist. A point system was developed to aid in the diagnosis by Rose et al. 2000. Molecular testing not reliable for making the diagnosis, only confirmatory. Management Eye Ophthalmology evaluation - at least annual starting in infancy. -Prescribe corrective lenses as early as possible -Prophylactic laser photocoagulation of vitreoretinopathy. Surgery as needed to remove cataracts or repair detachments. Avoid activities such as contact sports which may lead to retinal detachment. Patients should be aware of symptoms associated with retinal detachment. Hearing Loss Baseline audiogram. Hearing can be progressive, so follow-up evals are recommended. Arthropy Full skeletal eval including x-rays for mild spondyloepiphyseal dysplasia. Treatment is symptomatic with anti-inflammatory meds. Possible avoidance of high-impact activities. Cleft palate Deal with growth and feeding issues - bottle feed baby in seated position, use special bottles, frequent weight checks. Otolaryngology/craniofacial eval Test hearing regularly Treat otitis media aggressively, possibly PE tubes Cleft palate surgery ~9 months Eventual speech therapy. Mitral valve prolapse Screening for MVP with ECHO If MVP exists, need antibiotic prophylaxis for certain surgical procedures. Genetics Autosomal dominant inheritance Recurrence risk is 50% for each child of an affected parent. Prevalence of new gene mutations unknown Disease causing mutations in genes COL2A1, COL11A1, and COL11A2, but some families are not linked to any of these loci. COL2A1 gene (cause in 75% of families) Typically have type 1 vitreous anomaly and a high risk for retinal detachment, normal hearing or mild SNHL, and early-onset arthritis. COL11A1 Typically have type 2 vitreous anomaly and more severe hearing loss COL11A2 Causes "anocular" Stickler syn because protein is not expressed in the eye -a.k.a oto-spondylo-megaepiphyseal dysplasia (OSMED). Molecular Testing Clinical testing available for COL2A1 and COL11A1 Tulane University Health Sciences Center Matrix DNA Diagnostics Laboratory New Orleans, LA Contact: Charlene Crain, MBA, BSMT (ASCP) email:ccrain@tulane.edu phone: (504) 988-7706 fax: (504) 988-7704 Methodology: Direct DNA Research testing may be available for COL11A2 and mutations in unknown loci Geneclinics Pregnancy and Testing Option of prenatal testing exists for fetuses at 50% risk for Stickler syndrome if a mutation in COL2A1 or COL11A1 has been identified in the affected parent molecular testing performed either on sample from chorionic villus sampling (CVS) at about 10-12 weeks' gestation or amniocentesis at 16-18 weeks' gestation. Alternatively, or in conjunction with molecular genetic testing, ultrasound can be performed at 19-20 weeks gestation to detect cleft palate, HOWEVER not all individuals with Stickler have cleft palate and cleft palates is difficult to detect on ultrasound Detection somewhat dependent on position of the fetus Psychosocial Counseling Discuss patient experience with Stickler syndrome and perceived burden Discuss unaffected husband/partner's comfort-level with the diagnosis. Assess whether they are concerned about having a child with Stickler syndrome? Assess patient support systems. Address potential feelings of guilt. Assess whether she would like information about online support group Resources Parent and Infant Group (Craniofacial) Contact Tricia Bender for more information Stickler Involved People 15 Angeline Augusta, KS 67010 www.sticklers.org Stickler Syndrome Support Group PO Box 371 Walton-on-Thames Surrey KT12 2YS www.stickler.org.uk References GeneClinics web page: www.geneclinics.org, "Stickler Syndrome". "Stickler Involved People" web site: http://www.sticklers.org/sip/. Management of Genetic Syndromes. Edited by S.B. Cassidy and J.E. "Chapter 24: Stickler syndrome" by Wilkin, DJ, Liberfarb, RM, and Francomano, CA. Allanson. (2001) Wiley-Liss, Inc. Smith's Recognizable Syndromes. "Stickler Syndrome" pg 282-285. Notes The information in this outline was last updated in 2002.