Natural History of SURF1 Deficiency: A Retrospective Chart Review.

BACKGROUND: This retrospective chart review evaluated the clinical characteristics of SURF1-related neurological disease spectrum to better characterize the phenotypes. METHODS: Patient demographics, magnetic resonance imaging abnormalities, neurological events, motor abnormalities, and gastrointestinal and respiratory assistance were evaluated in 27 patients with genetically diagnosed SURF1 deficiency. RESULTS: The mean (S.D.) age of symptom onset collected from 13 patients was 19.7 (11.8) months. Mean (S.D.) age of diagnosis collected from 24 patients was 44.0 (45.1) months. The most common symptoms were gross motor delay (14 of 14), fine motor delay (10 of 11), verbal delay (9 of 10), and intellectual and learning disability (14 of 19). Neurological symptoms included ataxia (14 of 15), other abnormal movements (8 of 9), hypotonia (9 of 11), and dystonia (6 of 9). Three of nine reporting patients (33.3%) had a history of seizure, and 84.6% (11 of 13) had a history of regression/loss of acquired skills. Extraneurological clinical features included pulmonary complications (10 of 11) and feeding difficulties (13 of 13); cardiac complications were noted in three patients. Brainstem is frequently involved with the medulla and midbrain being the most common sites. As of July 2021, three patients were deceased. CONCLUSIONS: The most common clinical symptoms were motor delay, verbal delay, intellectual and learning disability, dysphagia, feeding difficulties, and reflux. Neurological presentations include ataxia, hypotonia, visual/ocular abnormalities, dystonia, and imaging abnormalities include basal ganglia and brainstem lesions. Although heterogeneous, SURF1 deficiency should be considered with these clinical and imaging presentations and may support earlier identification.

A case of Bainbridge-Ropers syndrome with breath holding spells and intractable epilepsy: challenges in diagnosis and management.

BACKGROUND: Bainbridge-Ropers syndrome is caused by monoallelic ASXL3 variants on chromosome 18. Clinical features include dysmorphic facies, developmental delay, intellectual disability, autistic traits, hypotonia, failure to thrive, seizures and hyperventilation. Breath-holding spells with choreathetoid movements have been previously described. CASE PRESENTATION: We describe an 11-year old boy who has daily intractable seizures reported since birth, developmental delay, autistic features and feeding difficulties. He was eventually found to have de novo, heterozygous pathogenic variant (c.1612G > T, p.E538*) in the ASXL3 gene. He has frequent episodes of breath-holding accompanied by dystonic posturing with right leg extension and head turning without ictal EEG correlate. The breath-holding spells have been refractory to several medication trials including iron supplementation, acetazolamide, and desipramine. CONCLUSIONS: This case represents a more severe phenotype of Bainbridge-Ropers Syndrome than previously described with refractory breath-holding spells with dystonia, intractable epilepsy, and progressive cerebral/cerebellar atrophy. Breath-holding spells cause significant morbidity, are poorly understood, and have very limited treatment options.

Autologous hematopoietic stem cell transplantation in a pediatric patient with aquaporin-4 neuromyelitis optica spectrum disorder.

We report on a child with an early and severe manifestation of an Aquaporin-4 (AQP-4) positive Neuromyelitis Optica Spectrum Disorder (NMOSD) who had a refractory disease course despite aggressive immunotherapy and underwent autologous hematopoietic stem cell transplant (AHSCT).

Aquaporin-4 neuromyelitis optica spectrum disorder in a 2-year-old girl: Diagnostic and treatment considerations.

We describe a case of an unusually early and severe manifestation of Aquaporin-4 (AQP-4) positive Neuromyelitis Optica Spectrum Disorder (NMOSD) in a two-year-old girl. We discuss learning points from her clinical presentation and highlight differences between pediatric and adult presentations of the disease. We argue that AQP-4 NMOSD should always be considered in the differential diagnosis for any child presenting with an acute neuroimmunological process given the morbidity associated with the condition and the importance of early diagnosis and treatment.

Long-term facilitation of breathing is absent after episodes of hypercapnic hypoxia in awake humans.

Despite the failure by many previous investigators to demonstrate a long-term facilitation of breathing following episodes of hypoxia in awake humans, we attempted to produce it using a pattern of hypercapnic hypoxic episodes similar to that experienced by obstructive sleep apnoea patients, reasoning that if long-term facilitation was relevant to these patients then it is appropriate to test the effectiveness of such episodes. Ten subjects drawn from the University student population were instrumented to measure ventilation, heart rate and end-tidal PCO2 and PO2 breath-by-breath while seated in a comfortable reclining chair. After an initial resting period breathing room air they experienced fifteen, 30-s episodes breathing 6% O2 and 5% CO2 separated by 90 s of breathing air. We examined the measured variables for an hour after the episodes but found no trends toward an increase in ventilation or decrease in end-tidal PCO2 that would indicate the presence of a long-term facilitation. We therefore concluded that long-term facilitation of ventilation was not demonstrated in awake humans using this pattern of stimuli.