Congenital cranial dysinnervation disorders (CCDDs) are a group of rare, nonprogressive conditions characterized by abnormal development of the cranial motor nerves and variable ocular motility deficits, ptosis, incomitant strabismus, and facial palsy. Advances in genetics and neuroimaging have revealed that these disorders result from defects in neuronal differentiation or axon guidance of the cranial motor neurons. Duane retraction syndrome, the most common CCDD, results from the absence of the abducens nerve and innervation of the lateral rectus by oculomotor nerve axons; causative genes include CHN1, MAFB, HOXA1, SALL4, and EBF3, although most cases do not have a genetic diagnosis. Congenital fibrosis of the extraocular muscles (CFEOM), results from variants in KIF21A, PHOX2A, TUBB3, or other tubulin genes, and affects the oculomotor and trochlear nerves. Horizontal gaze palsy with progressive scoliosis (HGPPS), caused by ROBO3 loss of function, arises from failure of axonal midline crossing in the brainstem. Moebius syndrome, defined by abducens and facial nerve palsies, has no identified genetic cause and may result from non-Mendelian causes. Additional CCDDs with atypical or syndromic presentations are linked to COL25A1, ECEL1, and ACKR3, although many do not have a genetic explanation. The expanding list of CCDD-associated genes highlights shared developmental pathways, including neuronal differentiation, axon guidance, and microtubule dynamics. Improved genetic diagnosis informs prognosis and multidisciplinary management. This review synthesizes current understanding of CCDDs, emphasizing the shift from phenotypic classification to molecular subtyping, and underscores the importance of ongoing research to resolve genetically unsolved cases and refine diagnostic and therapeutic strategies.

Horizontal gaze palsy with progressive scoliosis (HGPPS) is a rare neurodevelopmental disorder marked by the absence of horizontal eye movement and gradual progressive scoliosis during childhood. Here, we report two biological siblings that presented with a shared diagnosis; however, the curves are in opposite directions and one presents with dextrocardia. Two siblings presented with acute scoliosis and conjugate absence of horizontal gaze. The diagnosis was confirmed based on characteristic clinical presentation, congenital absence of horizontal gaze, and supportive radiographic imaging. Both patients were followed from early infancy through skeletal maturity with radiographs and clinical evaluations. Curve progression, response to conservative measures, and indications for surgical intervention were documented. Both patients developed progressive thoracic scoliosis despite early casting and bracing, with curves exceeding 70° by early adolescence ultimately requiring an anterior and posterior spinal fusion and instrumentation (PSFI). Postoperatively, both patients demonstrated stable spinal alignment and achieved satisfactory correction with long-term follow-up. Interestingly, evaluation of the radiographs demonstrates opposite convex thoracic curve patterns, each with an apex at T9, one with a left thoracic curve and an associated dextrocardia and the other with a right thoracic curve and normal left-sided heart position. This report provides rare long-term data spanning more than a decade with a unique phenotypic presentation among siblings. It is notable for their opposing curve directions-one right-sided and one left-sided with the presence of conjugate dextrocardia in the left thoracic scoliosis. These findings may suggest an underlying influence of asymmetric cardiothoracic development or potential link of blood supply pattern on spinal curve direction. Recognition of this unique phenomenon might offer new insight into the etiology of scoliosis in HGPPS and warrants further investigation into the developmental factors contributing to curve morphology.

This interventional case report documents the underlying genetic mutation, secondary muscle changes, and the result of surgical intervention in a patient presenting with synergistic convergence and esotropia. A 16-year-old patient underwent full ophthalmic examination, radiological imaging, and genetic testing. Diagnosis of horizontal gaze palsy with progressive scoliosis was confirmed, suggesting central miswiring as a cause of the synergistic convergence. Whole exome sequencing gene test revealed homozygous ROBO3 gene mutation (p.Leu888Arg) at a mutational hot spot with a GERP score of 4.88. Several computational analyses predicted the variant to be damaging. Bilateral medial rectus recessions of 7 and 8 mm were performed. Both medial rectus muscles were found tight, but not atrophic. Orthotropia and temporary resolution of synergistic convergence were documented. This case study reports a new mutation in the ROBO3 gene, and it is one of the few cases of central synergistic convergence that underwent surgical intervention and documenting secondary muscle changes.

To describe a rare inherited disorder in five patients presenting with horizontal gaze palsy along with characteristic abnormalities on neuroimaging. A retrospective review was conducted from January 2016 to December 2022 of all patients with the diagnosis of horizontal gaze palsy with progressive scoliosis (HGPPS). Neuroimaging was performed in all patients and genetic testing in those who consented. All five patients had limitation of abduction and adduction in both eyes on attempted horizontal gazes with intact elevation, depression, and convergence. Two patients presented with synergistic convergence. Esotropia requiring strabismus surgery was present in one patient. Magnetic resonance imaging of the brain and orbit in all patients showed brainstem hypoplasia with "split pons" sign and a "butterfly configuration" of the medulla, which are characteristic of HGPPS. Genetic analysis of 3 patients confirmed the presence of ROBO3 gene mutations. Scoliosis was noted in 2 patients. Early diagnosis and a multidisciplinary approach is important in the management of such cases. Phenotypic variations such as in the cases described may be observed in HGPPS.