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Stickler Syndrome

Posted By Alan Hakim, July 26, 2015

This webpage has been written for patients, the public and health and social care professionals. It was published as an article in the Spring 2015 HMSA Journal.

Introduction
First described by Dr Gunnar B Stickler in 1965, Stickler syndrome is a connective tissue condition that results in a distinctive facial appearance, eye abnormalities, hearing loss and joint problems including hypermobility. It is caused by mutations of certain genes responsible for the production of collagen. Unlike Col3 and Col5 in EDS, or COL1 in OI, the genes affected in Stickler syndrome are COL2 (accounting for 75% of cases), COL9, and COL11. There are two COL11 genes that lead to Stickler syndrome: COL11A1 and COL11A2. One important difference between them is that the COL11A2 gene defect does not affect the eye.

The syndrome is estimated to be present in 1 per 10,000 of the general population. Like all the other Heritable Disorders of Connective Tissue (HDCT) there are a range of signs and symptoms, and individuals can be affected in different ways. Some people have no major signs and no problems; some have most or all of them and experience a range of problems from the subtle to the severe. Also like many of the HDCT, Stickler syndrome is most often inherited as an autosomal dominant condition. The exception is the COL9 variant that is inherited in a ‘recessive’ way.

The signs, symptoms and complications of Stickler syndrome

Eyes:

Short-sightedness (myopia)

High risk of detachment of the retina (the light-sensitive layer at the back of the eye)

Early onset cataracts (clouding of the lens)

Glaucoma (due to high pressure within the eye)

Bones and Joints:

Both stiff and hypermobile joints

Early onset osteoarthritis (wear and tear arthritis, particularly at the hips)

Scoliosis (curvature of the spine)

Joint pain

Facial Characteristics:

A flat face (flat cheek bones) with a small nose, and

Little or no nasal bridge

Small upper jaw

Small lower jaw

Mouth: 

Cleft palate (an opening in the roof of the mouth). This may also lead to ear infections

High arched palate

Bifid uvula

Micrognathia (the lower jaw is shorter than normal)

These problems may lead to difficulties with speech, swallowing, and breathing.

Ears:

Hearing loss (as with visual impairment, this might for example manifest as learning difficulties (not intelligence) at school etc.

Glue ear in childhood caused by cleft palate

Heart:

Mitral valve prolapse

The Pierre Robin Sequence (PRS)
This is a rare trio of cleft palate, retrognathia (small lower jaw leading to an ‘over-bite’), and backward displacement of the tongue. The tongue may be too large for the space formed by the small lower jaw. Its backward displacement can then block the airway. PRS may arise spontaneously (in about 40% of cases) or a consequence of Sticklers syndrome, Foetal Alcohol syndrome and other rare conditions such as Treacher Colins’ syndrome.

Criteria for the diagnosis of Stickler syndrome
The diagnosis is based on both clinical findings and genetic tests, with Major and Minor. Each finding is given a certain number of points. A diagnosis requires the presence of at least 1 major criterion and 5 points or more in total. Hypermobility is not part of the diagnostic criteria.

Major Criteria (2 points for each criterion)

– Orofacial Cleft palate

– Ocular Characteristic vitreous changes or retinal abnormalities

– Auditory High frequency sensorineural deafness

Minor Criteria
(1 point for each criterion 1, 2, and 4, & max 2 points within criterion 3)

– Orofacial Malar hypoplasia, broad/flat nose, micro/retrognathia

– Auditory Hypermobile eardrum

– Skeletal Maximum of 2 points out of 3 for: Femoral head disease, slipped epiphysis, (and/or) Radiographic evidence of osteoarthritis below age 40 yrs (and/or) Kypho/scoliosis, spondylolisthesis

– Genetic Affected first degree relative OR presence of COL2A1, COL11A1 or COL11A2 gene mutation

Managing Stickler syndrome – Specialist input
Given the different concerns that can arise, like many of the HDCT a number of specialist health and social care services may become involved in supporting an individual and families. These might include:

Audiologists,

Cardiologists,

ENT surgeons,

maxillofacial and craniofacial surgeons,

Neonatologists and Paediatricians,

Nurses (specialist and school nursing),

Nutritionists,

Ophthalmologists,

Oral surgeons,

Orthodontics,

Orthopaedics,

Occupational therapists,

Physiotherapists,

Rheumatologists,

Social services, and

Speech and Language therapists.

Managing Stickler syndrome – Approaches to Care

Medical: e.g. pain relief, management of glaucoma,

Therapies for speech, and joint and muscle concerns (splints, braces, aids, physiotherapy),

Hearing aids,

Glasses and contact lenses, and regular eye checks,

Feeding aids, particularly critical in new borne and infants prior to any surgical correction to the palate, jaw and airway,

Specialist aids and care for protecting breathing / airways,

Educational support,

Surgery to e.g. eyes, jaw, palate, throat, and joints.

 

The detail of all the practical and surgical interventions is beyond the scope of this article.
For the vast majority with Stickler syndrome life expectancy is normal and individuals will lead full lives. However the complications described above may manifest and respond to treatment in varied ways such that for some individuals day to day function and ability may be affected in different and potentially life-changing ways.

To read more about Stickler syndrome please go to: www.stickler.org

Dr Alan J Hakim MA FRCPTIS-image

Consultant Physician and Rheumatologist, The Hospital of St John and St Elizabeth, London, Chief Medical Officer and Trustee, HMSA

Published 26th July 2015. Peer reviewed for HMSA Journal February 2015. Date of next review July 2017.

References

Ahmad N, Richards AJ, Murfett HC, Shapiro L, Scott JD, Yates JR, Norton J, Snead MP. Prevalence of mitral valve prolapse in Stickler syndrome. Am J Med Genet A. 2003;116A(3):234-7.

Ang A, Poulson AV, Goodburn SF et al. Retinal detachment and prophylaxis in type 1 Stickler syndrome. Ophthalmology. 2008;115(1):164-8.

Annunen S, Korkko J, Czarny M et al. Splicing mutations of 54-bp exons in the COL11A1 gene. Am J Hum Genet 1999; 65(4):974-83.

Antunes RB, Alonso N, Paula RG. Importance of early diagnosis of Stickler syndrome in newborns. J Plast Reconstr Aesthet Surg. 2012;65(8):1029-34.

Carroll C, Papaioannou D, Rees A, Kaltenthaler E. The clinical effectiveness and safety of prophylactic retinal interventions to reduce the risk of retinal detachment and subsequent vision loss in adults and children with Stickler syndrome: a systematic review. Health Technol Assess. 2011 Apr;15(16):iii-xiv, 1-62.

Couchouron T, Masson C. Early-onset progressive osteoarthritis with hereditary progressive ophthalmopathy or Stickler syndrome. Joint Bone Spine. 2011;78:45-9.

Flores RL, Tholpady SS, Sati S et al. The Surgical Correction of Pierre Robin Sequence: Mandibular Distraction Osteogenesis versus Tongue-Lip Adhesion. Plast Reconstr Surg. 2014;133:1433–9.

Lee KH, Hayward P. Retrospective review of Stickler syndrome patients with cleft palate 1997-2004. ANZ J Surg. 2008 Sep;78(9):764-6.

Liberfarb RM, Levy HP, Rose PS et al. The Stickler syndrome: genotype/phenotype correlation in 10 families with Stickler syndrome resulting from seven mutations in the type II collagen gene locus COL2A1. Genet Med. 2003; 5(1):21-7.

Rose PS, Ahn NU, Levy HP et al. Thoracolumbar spinal abnormalities in Stickler syndrome. Spine (Phila PA 1976). 2001;26(4):403-9.

Rose PS, Levy HP, Liberfarb RM et al. Stickler Syndrome: Clinical Characteristics and Diagnostic Criteria. Am J Med Genet. 2005;138A(3):199-207.

Smith MC, Senders CW. Prognosis of airway obstruction and feeding difficulty in the Robin sequence. Int J Pediatr Otorhinolaryngol. 2006 Feb;70(2):319-24.

Stickler GB, Belau PG, Farrell FJ et al. Hereditary Progressive Arthro-Ophthalmopathy. Mayo Clin Proc 1965; 40: 433–55.

 


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