Developmental central hypotonia: implications for counselling, prognosis, and management

Dan, Bernard

doi:10.1111/dmcn.15085

Cited by 4 publications

(2 citation statements)

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“…It is characterized by general hypotonia presenting as abnormal frog-like postures, reduced resistance to passive movement and excessive range of joint movement ( 26 , 27 ). It can be caused by multiple disorders of the muscles, the peripheral and most commonly the central nervous system ( 28 , 29 ). A self-limiting and remitting course is characteristic for benign congenital hypotonia.…”

Section: Discussionmentioning

confidence: 99%

A questionnaire-based investigation of the swimming puppy syndrome: 115 dogs

Rumpel,

Kölle,

Mille

et al. 2023

Front. Vet. Sci.

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Swimming Puppy Syndrome (SPS) is a benign reversible condition of unknown etiology in multiple dog breeds. Affected dogs show laterally abducted limbs and are unable to stand and walk on their own. The current knowledge of this condition derives from few case reports or small case series. Therefore, the aim of this study was to collect data on the clinical course from a large cohort of dogs with SPS with an online questionnaire supported by video footage. Potential risk factors were compared between 110 litters with SPS and 103 unaffected litters. SPS was reported in 115 dogs from 48 different breeds comprising a wide range of small, middle, and large breeds. Litters with SPS were significantly smaller than unaffected litters. Cesarean sections were reported more frequently in affected litters, but the overall rate of reported birth complications did not differ significantly from unaffected litters. Most puppies were able to stand and walk at a median age of 4.5 weeks (up to 12 weeks) and clinical signs resolved at a median age of six weeks (up to 12 weeks). Puppies from large breeds showed faster recovery than puppies from medium and small breeds. Occasionally, residual deficits were reported and only three dogs failed to recover. A clustering of SPS occurred in closely related litters in four kennels of four different dog breeds (Greater Swiss Mountain Dog, Golden Retriever, Miniature Bull Terrier, Norwich Terrier). The study shows the benign clinical course of SPS in a large cohort of puppies from multiple dog breeds. Potential risk factors including reports on birth complications, size and muscle mass compared to littermates and diet of the dam during pregnany were evaluated and no influence on the occurrence of SPS was identified.

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Section: Discussionmentioning

confidence: 99%

A questionnaire-based investigation of the swimming puppy syndrome: 115 dogs

Rumpel,

Kölle,

Mille

et al. 2023

Front. Vet. Sci.

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“…Many neurodevelopmental disorders are the result of genetic mutations and often target molecular pathways that impact protein synthesis, transcriptional or epigenetic regulation or synaptic signaling (Lewis and Kroll, 2018; Cardoso et al, 2019; Parenti et al, 2020). An early feature that is common to several neurodevelopmental defects is central hypotonia (low muscle tone), however, it remains unclear how the underlying biochemical and sensorimotor mechanisms can result in this feature (Dan, 2022).…”

Section: Introductionmentioning

confidence: 99%

Defects in exosome biogenesis are associated with sensorimotor defects in zebrafishvps4amutants

Shipman,

Gao,

Liu

et al. 2024

Preprint

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Mutations in humanVPS4Aare associated with neurodevelopmental defects, including motor delays and defective muscle tone.VPS4Aencodes a AAA-ATPase that is required for membrane scission, but how mutations inVPS4Alead to impaired control of motor function is not known. Here we identified a mutation in zebrafishvps4a, T248I, that affects sensorimotor transformation. In biochemical experiments we show that the T248I mutation reduces the ATPase activity of Vps4a and disassembly of its substrate, ESCRT filaments, which mediate membrane scission. Consistent with the established role for Vps4a in the endocytic pathway and exosome biogenesis,vps4aT248Imutants have enlarged endosomal compartments in the CNS and decreased numbers of circulating exosomes. Resembling the central form of hypotonia in humanVPS4Apatients, motor neurons and muscle cells are unaffected in mutant zebrafish as they react robustly to touch. Unlike somatosensory function, optomotor responses, vestibulospinal (VS), and acoustic startle reflexes are severely impaired invps4aT248Imutants, indicating a greater sensitivity of these circuits to the T248I mutation. ERG recordings indicate that visual ability is largely reduced in the mutants, however,in vivoimaging of tone-evoked responses in the inner ear and ascending auditory pathway show comparable activity. Further investigation of central pathways invps4aT248Imutants revealed that sensory cues failed to fully activate neurons in the VS and medial longitudinal fasciculus (MLF) nuclei that directly innervate motor neurons. Our results suggest that a defect in sensorimotor transformation underlies the profound yet selective effects on motor reflexes resulting from the loss of membrane scission mediated by Vps4a.

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