China
Africa
Explore chapters and articles related to this topic
Congenital Cranial Dysinnervation Disorder
Published in Vivek Lal, A Clinical Approach to Neuro-Ophthalmic Disorders, 2023
CHN1 gene is responsible for encoding signaling molecule α2-chimaerin and its mutation, or overexpression of wild-type α2-chimaerin results in stalling of axons of third cranial nerve with aberrant branching. Mutation of CHN1 gene can result in familial or isolated DRS. SALL4 is another identified gene in Duane's phenotype. HOXA1 genes are responsible for transcription encoding which is critical for hindbrain development and its mutation results in bilateral DRS, deafness, and autism (8, 19, 20).
A 7-year old female with arthrogryposis multiplex congenita, Duane retraction syndrome, and Marcus Gunn phenomenon due to a ZC4H2 gene mutation: a clinical presentation of the Wieacker-Wolff syndrome
Published in Ophthalmic Genetics, 2021
Deena Godfrey, Alcy Torres, Gena Heidary, Hovra Zahoor, Arthur Lee, Gerard Berry, Elizabeth Engle
DRS is a form of congenital strabismus characterized by limited horizontal eye movement coupled with globe retraction and reduction in palpebral fissure height on attempted adduction and, in some cases, up or downshoots of the eye (1). DRS is caused by failure of abducens motor neurons to innervate the lateral rectus muscle, which is innervated instead by an aberrant branch of the oculomotor nerve (1). In DRS, co-contraction of the medial rectus and lateral rectus muscles occurs as a result of this aberrant neuronal innervation (1). AMC refers to congenital non-progressive joint contractures involving at least two different body areas (2). Most AMC cases are secondary to nervous system defects that arise from environmental or genetic factors (3). Thus, motor neuron maldevelopment can lead to contractures in AMC and restricted horizontal eye movement in DRS (4). Both DRS and AMC have an incidence of approximately 1:1500–1:3000 live births (1). Significant research has been directed towards uncovering the genetic etiology of DRS and AMC. Familial DRS can follow autosomal dominant or recessive inheritance patterns, with pathogenic variants being identified CHN1, MAFB, and SALL4 among other genes (5). AMC has been associated with autosomal dominant, autosomal recessive, and X-linked inheritance, and over 400 AMC genes have been reported (6). Here, we report a child with both AMC and DRS who harbors a de novo ZC4H2 mutation, thereby confirming this association that was previously reported in two teenaged females (7).
Childhood Onset Strabismus: A Neurotrophic Factor Hypothesis
Published in Journal of Binocular Vision and Ocular Motility, 2021
Jolene C. Rudell, Jérome Fleuriet, Michael J. Mustari, Linda K. McLoon
Additional evidence that the main contributor to the development of childhood onset strabismus originates from the central nervous system comes from study of the rarest forms of strabismus, the congenital cranial dysinnervation disorders (CCDDs). The CCDDs are often called “congenital fibrosis of the extraocular muscles” or CFEOM. The majority of these rare genetic CCDDs result in strabismus due to abnormal axon growth in the motor nerves from one or more nuclei of the ocular motor complex.15,16 Mutations in the KIF21A gene causes CFEOM1 and CFEOM3.17KIF21A is a kinesin that is responsible for cargo delivery through retrograde and anterograde axonal transport, and the mutation results in oculomotor nerve loss and muscle atrophy. Similarly, CFEOM2 is caused by mutations in the ARIX/PHOX2A gene, which is critically important for the development and routing of cranial nerves III (oculomotor) and IV (trochlear).18 Interestingly, Ret, a glial cell line-derived neurotrophic factor (GDNF) receptor subunit, also is regulated in part by the PHOX2A gene,19 implicating down-stream neurotrophic factor alterations that could be the sequelae of these motor nerve abnormalities. The absence of the abducens nerve in Duane retraction syndrome can be caused by mutations in SALL4, ROBO3, HOXA1, and the CHN1 gene, which results in mutations in the α2-chimaerin protein which alters normal cytoskeletal dynamics and abducens nerve formation.16,20,21 While rare, these CCDDs demonstrate that some forms of strabismus can result from primary ocular motor nerve maldevelopment.
Concomitant Unilateral Duane Retraction Syndrome and Contralateral Brown’s Syndrome
Published in Journal of Binocular Vision and Ocular Motility, 2023
Arash Mirmohammadsadeghi, Mohammad Reza Akbari, Sahel Soltani Shahgholi
Incidence of Brown syndrome was reported as 1 per 350 to 450 strabismus cases6 and incidence of Duane retraction syndrome was reported as 1–4 per 100 strabismus cases.3 Most researchers proposed teratogenic role in sporadic DRS.1 Genetic research of familial DRS demonstrated specific gene mutation (CHN1, MAFB, or SALL4).7