U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Maternally-inherited Leigh syndrome(MILS)

MedGen UID:
443976
Concept ID:
C2931092
Disease or Syndrome
Synonyms: Leigh disease, maternally inherited; Subacute necrotizing encephalomyelopathy maternally inherited
SNOMED CT: Maternally inherited Leigh syndrome (717052002); Maternally inherited Leigh disease (717052002); Maternally inherited infantile subacute necrotizing encephalopathy (717052002)
Modes of inheritance:
Mitochondrial inheritance
MedGen UID:
165802
Concept ID:
C0887941
Genetic Function
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on the mitochondrial genome. Because the mitochondrial genome is essentially always maternally inherited, a mitochondrial condition can only be transmitted by females, although the condition can affect both sexes. The proportion of mutant mitochondria can vary (heteroplasmy).
 
Monarch Initiative: MONDO:0016814
OMIM®: 500017; 516060; 590050; 590105
Orphanet: ORPHA255210

Definition

A rare subtype of Leigh syndrome with clinical characteristics of encephalopathy, lactic acidosis, seizures, cardiomyopathy, respiratory disorders and developmental delay. Onset in infancy or early childhood resulting from maternally-inherited mutations in mitochondrial DNA. [from SNOMEDCT_US]

Clinical features

From HPO
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Developmental regression
MedGen UID:
324613
Concept ID:
C1836830
Disease or Syndrome
Loss of developmental skills, as manifested by loss of developmental milestones.
Focal T2 hyperintense basal ganglia lesion
MedGen UID:
892349
Concept ID:
C4024926
Finding
A lighter than expected T2 signal on magnetic resonance imaging (MRI) of the basal ganglia. This term refers to a localized hyperintensity affecting a particular region of the basal ganglia.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
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.
Increased circulating lactate concentration
MedGen UID:
332209
Concept ID:
C1836440
Finding
Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35).
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Decreased activity of mitochondrial respiratory chain
MedGen UID:
892840
Concept ID:
C4024609
Finding
Decreased activity of the mitochondrial respiratory chain.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Maternally-inherited Leigh syndrome in Orphanet.

Recent clinical studies

Etiology

Spangenberg L, Graña M, Greif G, Suarez-Rivero JM, Krysztal K, Tapié A, Boidi M, Fraga V, Lemes A, Gueçaimburú R, Cerisola A, Sánchez-Alcázar JA, Robello C, Raggio V, Naya H
Mitochondrion 2016 May;28:54-9. Epub 2016 Mar 24 doi: 10.1016/j.mito.2016.03.006. PMID: 27017994
Debray FG, Lambert M, Allard P, Mitchell GA
J Child Neurol 2010 Aug;25(8):1000-2. Epub 2010 May 14 doi: 10.1177/0883073809351983. PMID: 20472868
Debray FG, Lambert M, Lortie A, Vanasse M, Mitchell GA
Am J Med Genet A 2007 Sep 1;143A(17):2046-51. doi: 10.1002/ajmg.a.31880. PMID: 17663470
Carrozzo R, Rizza T, Stringaro A, Pierini R, Mormone E, Santorelli FM, Malorni W, Matarrese P
J Neurochem 2004 Jul;90(2):490-501. doi: 10.1111/j.1471-4159.2004.02505.x. PMID: 15228605

Diagnosis

Spangenberg L, Graña M, Greif G, Suarez-Rivero JM, Krysztal K, Tapié A, Boidi M, Fraga V, Lemes A, Gueçaimburú R, Cerisola A, Sánchez-Alcázar JA, Robello C, Raggio V, Naya H
Mitochondrion 2016 May;28:54-9. Epub 2016 Mar 24 doi: 10.1016/j.mito.2016.03.006. PMID: 27017994
Debray FG, Lambert M, Allard P, Mitchell GA
J Child Neurol 2010 Aug;25(8):1000-2. Epub 2010 May 14 doi: 10.1177/0883073809351983. PMID: 20472868
Shuk-kuen Chau C, Kwok KL, Ng DK, Lam CW, Tong SF, Chan YW, Siu WK, Yuen YP
Sleep Breath 2010 Jun;14(2):161-5. Epub 2009 Aug 11 doi: 10.1007/s11325-009-0288-9. PMID: 19669818
Finsterer J
Acta Neurol Scand 2007 Jul;116(1):1-14. doi: 10.1111/j.1600-0404.2007.00836.x. PMID: 17587249
Ciafaloni E, Santorelli FM, Shanske S, Deonna T, Roulet E, Janzer C, Pescia G, DiMauro S
J Pediatr 1993 Mar;122(3):419-22. doi: 10.1016/s0022-3476(05)83431-6. PMID: 8095070

Therapy

Spangenberg L, Graña M, Greif G, Suarez-Rivero JM, Krysztal K, Tapié A, Boidi M, Fraga V, Lemes A, Gueçaimburú R, Cerisola A, Sánchez-Alcázar JA, Robello C, Raggio V, Naya H
Mitochondrion 2016 May;28:54-9. Epub 2016 Mar 24 doi: 10.1016/j.mito.2016.03.006. PMID: 27017994

Prognosis

Leshinsky-Silver E, Lev D, Malinger G, Shapira D, Cohen S, Lerman-Sagie T, Saada A
Mol Genet Metab 2010 May;100(1):65-70. Epub 2010 Feb 10 doi: 10.1016/j.ymgme.2010.02.002. PMID: 20202874
Debray FG, Lambert M, Lortie A, Vanasse M, Mitchell GA
Am J Med Genet A 2007 Sep 1;143A(17):2046-51. doi: 10.1002/ajmg.a.31880. PMID: 17663470
Shtilbans A, Shanske S, Goodman S, Sue CM, Bruno C, Johnson TL, Lava NS, Waheed N, DiMauro S
J Child Neurol 2000 Nov;15(11):759-61. doi: 10.1177/088307380001501109. PMID: 11108511
Santorelli FM, Mak SC, Vazquez-Memije ME, Shanske S, Kranz-Eble P, Jain KD, Bluestone DL, De Vivo DC, DiMauro S
Pediatr Res 1996 May;39(5):914-7. doi: 10.1203/00006450-199605000-00028. PMID: 8726250

Clinical prediction guides

Licchetta L, Ferri L, La Morgia C, Zenesini C, Caporali L, Lucia Valentino M, Minardi R, Fulitano D, Di Vito L, Mostacci B, Alvisi L, Avoni P, Liguori R, Tinuper P, Bisulli F, Carelli V
Ann Clin Transl Neurol 2021 Mar;8(3):704-710. Epub 2021 Jan 21 doi: 10.1002/acn3.51259. PMID: 33476484Free PMC Article
Kucharczyk R, Rak M, di Rago JP
Biochim Biophys Acta 2009 May;1793(5):817-24. Epub 2009 Mar 6 doi: 10.1016/j.bbamcr.2009.02.011. PMID: 19269308
Debray FG, Lambert M, Lortie A, Vanasse M, Mitchell GA
Am J Med Genet A 2007 Sep 1;143A(17):2046-51. doi: 10.1002/ajmg.a.31880. PMID: 17663470
Cortés-Hernández P, Vázquez-Memije ME, García JJ
J Biol Chem 2007 Jan 12;282(2):1051-8. Epub 2006 Nov 22 doi: 10.1074/jbc.M606828200. PMID: 17121862

Recent systematic reviews

Finsterer J
J Clin Neuromuscul Dis 2023 Mar 1;24(3):140-146. doi: 10.1097/CND.0000000000000422. PMID: 36809201

Supplemental Content

Table of contents

    Clinical resources

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...