Congenital cranial dysinnervation disorders (CCDDs) represent a distinct group of strabismus syndromes that result from congenital abnormalities or absence of one or more cranial nerves, leading to primary or secondary aberrant innervation of extraocular muscles by other cranial nerves.
Duane Retraction Syndrome (DRS)
Research has shown that patients with DRS often have an absent or impaired abducens nerve nucleus, resulting in paradoxical innervation of the lateral rectus muscle by the oculomotor nerve. The clinical features include limited ocular motility, globe retraction, and abnormal head posture.
Classification:
DRS is clinically divided into three types:
- Type 1: Limited abduction in the affected eye with no significant limitation of adduction; esotropia may be present.
- Type 2: Limited adduction in the affected eye with no significant limitation of abduction; exotropia may be present.
- Type 3: Both abduction and adduction are limited in the affected eye; there may be no strabismus or associated esotropia or exotropia.
A rare variant, known as the synergistic divergence type of DRS, is characterized by outward movement of the eyes during attempts at adduction.
Diagnosis
Most patients exhibit limited abduction, globe retraction with narrowing of the palpebral fissure during adduction, and palpebral fissure widening during abduction. Vertical upshoot and/or downshoot phenomena are often observed, along with compensatory head posture. The majority of patients maintain good binocular single vision and rarely develop amblyopia. Forced duction tests typically reveal restriction. The condition usually affects only one eye, more commonly the left, with about 15% of cases involving both eyes.
Treatment
Patients without significant strabismus or abnormal head posture in primary gaze do not require treatment. Surgical intervention may be considered for those with significant compensatory head posture, primary gaze deviation, or noticeable globe retraction and vertical deviations. The primary goal of surgery is to improve eye alignment and head posture to achieve binocular single vision in the primary field of gaze, as it does not typically restore ocular motility. The surgical approach focuses primarily on weakening procedures. Strengthening procedures are generally avoided as they may exacerbate globe retraction postoperatively.
Congenital Fibrosis of the Extraocular Muscles (CFEOM)
Diagnosis
CFEOM can be classified into three types:
CFEOM Type 1 (CFEOM1)
This is the most common and classical form of CFEOM, primarily caused by mutations in the KIF21A gene and inherited in an autosomal dominant manner. Germline mosaic mutations may lead to confusion with autosomal recessive inheritance patterns. MRI studies in these patients often show hypoplasia of the levator palpebrae superioris and superior rectus muscles, suggesting congenital absence of the superior branch of the oculomotor nerve. The size of the oculomotor nerve emanating from the brainstem is reduced, and abnormalities in the fourth and sixth cranial nerves are also observed. Clinical features include bilateral symmetrical ptosis, downgaze deviation in both eyes, a positive forced duction test, limited upgaze with varying degrees of horizontal gaze limitation, and compensatory chin-up head posture.
CFEOM Type 2 (CFEOM2)
This rare form is primarily caused by mutations in the PHOX2A gene, inherited in an autosomal recessive manner. Genetic studies have confirmed that primary maldevelopment of the third and fourth cranial nerve nuclei underlies this condition. Patients exhibit bilateral ptosis, large-angle exotropia, and severe horizontal and vertical gaze limitations.
CFEOM Type 3 (CFEOM3)
This non-classical form is hypothesized to occur due to mutations in genes such as KIF21A, TUBB3, TUBB2B, or TUBA1A, resulting in varying degrees of developmental defects in the oculomotor nerve. The condition is inherited in an autosomal dominant manner. Any patient from a CFEOM1 family not meeting the diagnostic criteria for CFEOM1 is classified as CFEOM3. The condition can involve one eye or both eyes, and ocular motility can range from complete to mild limitation. A positive forced duction test is typically observed.
Treatment
The primary aims of surgery are to correct or improve strabismus and compensatory head posture in primary gaze. There is typically no improvement in ocular motility following surgery. The surgical approach involves large recessions of affected muscles without any shortening procedures. Due to the frequent absence or marked impairment of Bell’s phenomenon in these patients, ptosis correction surgery should be approached with caution.