Hypotonia (HP:0001252)
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Synonyms: Low muscle tone, Low or weak muscle tone, Muscle hypotonia, Muscular hypotonia, Central hypotonia, Peripheral hypotonia
Comment: Hypotonia can be caused by abnormalities of the central nervous system, any element of the motor unit (including the lower motoneuron), or both. Hypotonia is not a specific diagnosis, but can be observed in hundreds of genetic and other diseases. The first distinction to make when assessing a child with hypotonia is whether decreased muscle tone is a result of an abnormality of the central nervous system (CNS), peripheral neuromuscular system, or a combined abnormality involving both. Clinical findings suggestive of an abnormality of the CNS may include hyperreflexia, cognitive developmental delay, and seizures. In contrast, physical findings pointing towards a neuromuscular origin may include weakness, lack of antigravity movements, muscle atrophy, fasciculations, and/or diminished reflexes, most often in the context of normal cognitive function. The HPO term does not distinguish between these etiologies. Additional HPO terms should be used as required to describe associated features.
Pubmed References: PMID:21418198
Cross References: MSH:D009123, SNOMEDCT_US:398151007, SNOMEDCT_US:398152000, UMLS:C0026827
KEGG Pathway
| Index | Name | P-value | Adjusted p-value | Odds Ratio | Combined score |
| 1 | Oxidative phosphorylation | 1.197e-22 | 1.317e-21 | 198670.00 | 10028275.58 |
| 2 | Retrograde endocannabinoid signaling | 3.613e-22 | 1.987e-21 | 198520.00 | 9801417.00 |
| 3 | Non-alcoholic fatty liver disease | 5.818e-22 | 2.133e-21 | 198450.00 | 9703402.49 |
| 4 | Diabetic cardiomyopathy | 9.277e-21 | 2.551e-20 | 197970.00 | 9131721.76 |
| 5 | Thermogenesis | 3.629e-20 | 7.983e-20 | 197680.00 | 8848725.20 |
GO: Biological Process
| Index | Name | P-value | Adjusted p-value | Odds Ratio | Combined score |
| 1 | mitochondrial electron transport, NADH to ubiquinone (GO:0006120) | 2.254e-28 | 4.958e-27 | 199610.00 | 12707139.91 |
| 2 | mitochondrial respiratory chain complex I assembly (GO:0032981) | 1.850e-26 | 1.357e-25 | 199420.00 | 11816020.17 |
| 3 | NADH dehydrogenase complex assembly (GO:0010257) | 1.850e-26 | 1.357e-25 | 199420.00 | 11816020.17 |
| 4 | aerobic electron transport chain (GO:0019646) | 1.407e-25 | 7.205e-25 | 199300.00 | 11404606.96 |
| 5 | mitochondrial ATP synthesis coupled electron transport (GO:0042775) | 1.637e-25 | 7.205e-25 | 199290.00 | 11373779.66 |
GO: Molecular Function
| Index | Name | P-value | Adjusted p-value | Odds Ratio | Combined score |
| 1 | NADH dehydrogenase (quinone) activity (GO:0050136) | 5.000e-25 | 1.000e-24 | 6910.62 | 386684.82 |
| 2 | NADH dehydrogenase (ubiquinone) activity (GO:0008137) | 5.000e-25 | 1.000e-24 | 6910.62 | 386684.82 |
| 3 | oxidoreduction-driven active transmembrane transporter activity (GO:0015453) | 7.535e-23 | 1.005e-22 | 3662.63 | 186574.14 |
| 4 | NADH dehydrogenase activity (GO:0003954) | 0.000004719 | 0.000004719 | 999.25 | 12254.80 |
GO: Cellular Component
| Index | Name | P-value | Adjusted p-value | Odds Ratio | Combined score |
| 1 | mitochondrial respiratory chain complex I (GO:0005747) | 5.216e-28 | 4.173e-27 | 199580.00 | 12537732.35 |
| 2 | respiratory chain complex I (GO:0045271) | 5.216e-28 | 4.173e-27 | 199580.00 | 12537732.35 |
| 3 | mitochondrial membrane (GO:0031966) | 4.573e-17 | 2.439e-16 | 195310.00 | 7348319.17 |
| 4 | mitochondrial inner membrane (GO:0005743) | 7.582e-16 | 3.033e-15 | 554.98 | 19322.03 |
| 5 | organelle inner membrane (GO:0019866) | 1.232e-15 | 3.944e-15 | 524.86 | 18018.26 |
Hub genes predicted as biomarkers & predicted FDA approved drugs
| Hub Genes (ranked) | FDA-Approved Drugs |
| NDUFS3 | – |
| NDUFA9 | – |
| NDUFA2 | – |
| NDUFC2 | – |
| NDUFA6 | – |
| NDUFA12 | – |
| NDUFA1 | – |
| NDUFA8 | – |
| NDUFB10 | – |
| NDUFB11 | – |
