メビウス症候群

PURPOSE: To report the surgical outcomes of the treatment of vertical deviation in patients with Möbius syndrome. METHODS: A retrospective review of the medical records of patients diagnosed with Möbius syndrome treated at the Ricardo Gutiérrez Children's Hospital between 2010 and 2024 was performed. Age, sex, and horizontal and vertical ocular deviations before and after surgery were recorded. Ocular deviation was measured using the alternate prism and cover test or Krimsky test according to patient cooperation. RESULTS: Sixty-two children were included, of whom 18 underwent surgical treatment. Most surgically treated patients presented with esotropia and were managed with bilateral medial rectus recession, with a mean recession of 7 mm (range: 4-12 mm). The mean preoperative horizontal deviation was 53 prism diopters (PD) of esotropia (range: 25-70 PD). Only 2 of 62 patients presented with exotropia. Vertical deviation was clinically evident in 14 of 62 patients, but only 5 underwent surgical correction. In all surgically treated cases, the vertical deviation corresponded to dissociated vertical deviation (DVD). One patient underwent bilateral superior rectus recession combined with horizontal surgery, one patient underwent unilateral superior rectus recession, and three patients underwent inferior rectus plication as a second procedure, achieving excellent postoperative alignment. CONCLUSIONS: Although esotropia with bilateral abduction limitation represents the predominant pattern in Möbius syndrome, vertical deviation is clinically evident in almost one quarter of patients. Inferior rectus plication proved to be a safe and effective technique for the surgical resolution of hypertropia in these cases.

BACKGROUND: The facial vein is the standard recipient vessel in facial reanimation surgery. Its complete absence is rarely described but may cause major challenges during free functional muscle transfer (FFMT). This study aimed to determine the prevalence and predictors of facial vein absence and assess its surgical relevance in facial reanimation patients. METHODS: A retrospective analysis of 198 patients who underwent FFMT between 2005 and 2025 was performed. Facial vein presence was evaluated intraoperatively, and all patients had preoperative Doppler ultrasonography. Potential predictors were analyzed using logistic regression and Fisher's exact test. RESULTS: Facial vein aplasia occurred in 12 patients. Aplasia was significantly associated with congenital etiology and syndromic palsy, especially Moebius syndrome. No associations with age, sex, operative time, or complications were found. CONCLUSIONS: Facial vein aplasia is strongly linked to congenital and syndromic palsy. Preoperative Doppler ultrasonography is recommended for identifying venous anomalies and optimizing surgical planning. TRIAL REGISTRATION: Freiburger Register Klinischer Studien (FRKS): Number FRKS005811.

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.

The ability of immunomodulatory mesenchymal stromal cells (MSCs) to improve COVID-19-associated acute respiratory distress syndrome (ARDS) in clinical trials is uncertain. We assessed whether freshly cultured umbilical cord (UC)-derived MSCs improved outcomes in patients with severe COVID-19 ARDS. We enrolled 37 patients with severe COVID-19 ARDS: 15 in the phase 1 dose escalation and open label extension studies (NCT04400032), and 22 patients in the phase 2b randomized clinical trial (NCT04865107). Delivery of up to 270 × 106 MSCs in three divided daily doses was well tolerated and resulted in qualitative improvement in all clinical outcomes. Furthermore, MSCs resulted in resolution of lymphopenia, consistent with an important immunomodulatory effect, with significant improvement in patient reported quality-of-life measures (SF-36) at 6 months pointing to possible durable clinical effects. These findings suggest a potential benefit of freshly cultured, UC-MSCs in severe COVID-19 ARDS, associated with biological evidence of favorable immunomodulatory activity.

Moebius syndrome is a rare, non-progressive congenital disorder, most commonly characterized by impairment of the abducens (VI) and facial (VII) cranial nerves, resulting in facial palsy and limited ocular abduction. A broad spectrum of associated clinical manifestations includes craniofacial abnormalities, limb malformations, and neuromotor developmental delay. Sleep disorders are frequently reported in these patients, most often related to sleep-disordered breathing. In contrast, rapid eye movement (REM) sleep behavior disorder (RBD) is exceptionally rare, both in pediatric patients and in association with this syndrome. We report the case of a 13-year-old male diagnosed with Moebius syndrome in the neonatal period, who developed recurrent episodes of nocturnal agitation, vocalizations, and dream enactment behaviors. Polysomnography demonstrated structural alterations of REM sleep with reduced muscle atonia and abnormal motor activity, findings consistent with RBD. Despite the implementation of sleep hygiene measures and pharmacological therapy, clinical response was limited. This case underscores the importance of actively investigating sleep disturbances in Moebius syndrome, not only to address the more common sleep-related breathing disorders but also to recognize rare conditions, such as RBD, which may significantly impact quality of life. Given the scarcity of evidence on pediatric RBD, particularly in association with congenital neurological syndromes, further research is needed to improve diagnostic and therapeutic strategies.