Stickler Syndrome

Author: Fred F. Ferri, MD

Definition

Stickler syndrome is a group of hereditary connective tissue diseases characterized by various ocular signs, bone and joint disorders, distinct facial features, and sensorineural deafness (seen in 10% of cases).

Synonyms

Stickler syndrome type 1: STL1, vitreous type 1, membranous vitreous type, arthroophthalmopathy, hereditary progressive, acute otitis media (AOM)
Stickler syndrome type 2: STL2, vitreous type 2, beaded vitreous type
Stickler syndrome type 3: STL3, Stickler syndrome nonocular type

ICD-10CM CODES
Q87		Congenital malformation syndromes predominantly affecting facial appearance
Q89.8		Other specified congenital malformations

Epidemiology & Demographics

Incidence:

At birth estimated around 1/7500

Prevalence:

1 to 9/100,000

Predominant Sex & Age:

Pediatric population

Risk Factors:

Family history given inheritance patterns

Genetics:

Inheritance is primarily autosomal dominant, though it can also be autosomal recessive and is genetically heterogeneous. Prenatal diagnosis is possible in families in which the mutation has been identified.

Physical Findings & Clinical Presentation

•Clinical features include facial changes, eye abnormalities, hearing loss, and arthritis.
•Facies: Flat midface, depressed nasal bridge, short nose, anteverted nares, micrognathia. Soft palate cleft is possible, associated with Pierre Robin sequence.
1. 1.Pierre Robin sequence can be an isolated abnormality or be a part of another syndrome; it results from hypoplasia of the mandible, leading to posterior displacement of the tongue (glossoptosis).
•Eyes: Abnormal architecture of the vitreous gel is pathognomonic, associated with high myopia; retinal detachment (ablatio retinae) is common (occurs in nearly 50%, bilateral in 40%); cataracts.
•Joint/bone: Joint hypermobility, early age of onset of arthritis.
•Hearing: Hearing loss can be sensorineural and/or conductive. Deafness can occur.
•Other: Mitral valve prolapse.

Etiology

The following mutations are autosomal dominant:

•Stickler syndrome type 1: Mutations in COL2A1 gene (12q13.11-q13.2)
•Stickler syndrome type 2: Mutations in COL11A1 gene (1p21)
•Stickler syndrome type 3: Mutations in COL11A2 gene (6p21.3)
•Mutations in COL9A1, COL9A2, and COL9A3 are inherited in autosomal recessive manner

Diagnosis ⬆ ⬇

Differential Diagnosis

•Marshall syndrome
•Wagner syndrome
•Weissenbacher-Zweymüller syndrome
•Marfan syndrome

Workup

•Diagnosis is based on clinical features
•Ophthalmology evaluation; slit-lamp evaluation is difficult in infants and young children
•Maxillofacial assessment if evidence of midline cleft
•Hearing testing

Laboratory Tests

Genetic testing can be done to confirm the diagnosis when there is clinical suspicion. Given inheritance patterns, other family members also may be tested for further information.

Imaging Studies

Joint x-rays can be considered depending on symptoms.

Treatment ⬆ ⬇

Treatment is primarily supportive and depends on involvement.

•Ophthalmology evaluation with routine long-term follow-up given the high risk of retinal detachment.
•Corrective lenses to be prescribed as early as possible. May need laser photocoagulation, surgical interventions of retinal detachment or tears.
•Surgical evaluations and treatment if cleft palate is present.
•Rheumatology or orthopedic evaluation if joint complaints. Physical therapy can be helpful. Joint replacements may ultimately be required.
•Potential hearing aids. Speech therapy if cleft is present.
•Educational assessments, though intelligence is normal. Hearing or visual impairments can lead to difficulties.

Disposition

Prognosis is generally good, but varies based on organ involvement and symptoms.

Referral

Ophthalmology, craniofacial, ear nose throat (ENT), rheumatology

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Basic Information ⬇

Diagnosis ⬆ ⬇

Treatment ⬆ ⬇

Pearls & Considerations ⬆