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Fetal akinesia-cerebral and retinal hemorrhage syndrome(LCCS5)

MedGen UID:
1631944
Concept ID:
C4706410
Disease or Syndrome
Synonyms: Lethal congenital contracture syndrome 5; MYOPATHY, CENTRONUCLEAR, LETHAL, AUTOSOMAL RECESSIVE
SNOMED CT: Lethal congenital contracture syndrome type 5 (763346009); Fetal akinesia, cerebral and retinal hemorrhage syndrome (763346009)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): DNM2 (19p13.2)
 
Monarch Initiative: MONDO:0014149
OMIM®: 615368
Orphanet: ORPHA363409

Definition

Lethal congenital contracture syndrome-5 (LCCS5) is an autosomal recessive disorder characterized by decreased fetal movements, joint contractures, hypotonia, skeletal abnormalities with thin bones, and brain and retinal hemorrhages (Koutsopoulos et al., 2013). For a general phenotypic description and a discussion of genetic heterogeneity of LCCS, see LCCS1 (253310). [from OMIM]

Clinical features

From HPO
Subdural hemorrhage
MedGen UID:
6775
Concept ID:
C0018946
Pathologic Function
Hemorrhage occurring between the dura mater and the arachnoid mater.
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Decreased nerve conduction velocity
MedGen UID:
347509
Concept ID:
C1857640
Finding
A reduction in the speed at which electrical signals propagate along the axon of a neuron.
EEG with burst suppression
MedGen UID:
369943
Concept ID:
C1969156
Finding
The burst suppression pattern in electroencephalography refers to a characteristic periodic pattern of low voltage (<10 microvolts) suppressed background and a relatively shorter pattern of higher amplitude slow, sharp, and spiking complexes.
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.
Congenital contracture
MedGen UID:
83066
Concept ID:
C0332878
Congenital Abnormality
One or more flexion contractures (a bent joint that cannot be straightened actively or passively) that are present at birth.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Thin ribs
MedGen UID:
98095
Concept ID:
C0426818
Finding
Ribs with a reduced diameter.
Centrally nucleated skeletal muscle fibers
MedGen UID:
330782
Concept ID:
C1842170
Finding
An abnormality in which the nuclei of sarcomeres take on an abnormally central localization (or in which this feature is found in an increased proportion of muscle cells).
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Polyhydramnios
MedGen UID:
6936
Concept ID:
C0020224
Pathologic Function
The presence of excess amniotic fluid in the uterus during pregnancy.
Decreased fetal movement
MedGen UID:
68618
Concept ID:
C0235659
Finding
An abnormal reduction in quantity or strength of fetal movements.
Retinal hemorrhage
MedGen UID:
11210
Concept ID:
C0035317
Pathologic Function
Hemorrhage occurring within the retina.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFetal akinesia-cerebral and retinal hemorrhage syndrome

Recent clinical studies

Etiology

Merle H, Chassery M, Béral L, Najioullah F, Cabié A, Césaire R, Fléchelles O, Pignol J, Errera MH, Ventura E, Grant R, Fontanet A, David T, Tressières B, Hoen B
JAMA Ophthalmol 2022 Oct 1;140(10):994-1001. doi: 10.1001/jamaophthalmol.2022.3405. PMID: 36048466Free PMC Article
Dedania VS, Ozgonul C, Besirli CG
Ophthalmic Surg Lasers Imaging Retina 2018 Sep 1;49(9):e83-e88. doi: 10.3928/23258160-20180907-12. PMID: 30222824
Kuhli-Hattenbach C, Hofmann C, Wenner Y, Koch F, Kohnen T
J Cataract Refract Surg 2016 May;42(5):759-67. doi: 10.1016/j.jcrs.2016.02.040. PMID: 27255253
Gonzalez VH, Ober RR, Borchert MS, Bui KC, Ramos AD, Stout AU
Retina 1993;13(3):202-7. doi: 10.1097/00006982-199313030-00003. PMID: 8235100
Acquaye JK, Omer A, Ganeshaguru K, Sejeny SA, Hoffbrand AV
Br J Haematol 1985 May;60(1):99-108. doi: 10.1111/j.1365-2141.1985.tb07390.x. PMID: 2408655

Diagnosis

Schiller ER, Kalafatis NE, Shields CL
J AAPOS 2022 Dec;26(6):330-333. Epub 2022 Sep 17 doi: 10.1016/j.jaapos.2022.08.260. PMID: 36126880
Merle H, Chassery M, Béral L, Najioullah F, Cabié A, Césaire R, Fléchelles O, Pignol J, Errera MH, Ventura E, Grant R, Fontanet A, David T, Tressières B, Hoen B
JAMA Ophthalmol 2022 Oct 1;140(10):994-1001. doi: 10.1001/jamaophthalmol.2022.3405. PMID: 36048466Free PMC Article
Esmer AC, Sivrikoz TS, Gulec EY, Sezer S, Kalelioglu I, Has R, Yuksel A
J Ultrasound Med 2016 Oct;35(10):2285-91. Epub 2016 Aug 31 doi: 10.7863/ultra.15.11040. PMID: 27582535
Mian M, Shah J, Dalpiaz A, Schwamb R, Miao Y, Warren K, Khan S
Fetal Pediatr Pathol 2015 Jun;34(3):169-75. Epub 2015 Jan 23 doi: 10.3109/15513815.2014.999394. PMID: 25616019
Gonzalez VH, Ober RR, Borchert MS, Bui KC, Ramos AD, Stout AU
Retina 1993;13(3):202-7. doi: 10.1097/00006982-199313030-00003. PMID: 8235100

Therapy

Kaaroud H, Beji S, Guermazi S, Moussa FB, Hamida FB, Ezzine S, Abdallah TB, El Younsi F, Kheder A
Saudi J Kidney Dis Transpl 2008 Mar;19(2):227-31. PMID: 18310872
Gonzalez VH, Ober RR, Borchert MS, Bui KC, Ramos AD, Stout AU
Retina 1993;13(3):202-7. doi: 10.1097/00006982-199313030-00003. PMID: 8235100

Prognosis

Himes RW, Chiou EH, Queliza K, Shouval DS, Somech R, Agarwal S, Jajoo K, Ziegler DS, Kratz CP, Huang J, Lucas TL, Myers KC, Nelson AS, DiNardo CD, Alter BP, Giri N, Khincha PP, McReynolds LJ, Dufour C, Pierri F, Goldman FD, Sherif Y, Savage SA, Miloh T, Bertuch AA
J Pediatr 2021 Mar;230:55-61.e4. Epub 2020 Sep 21 doi: 10.1016/j.jpeds.2020.09.038. PMID: 32971146
Dedania VS, Ozgonul C, Besirli CG
Ophthalmic Surg Lasers Imaging Retina 2018 Sep 1;49(9):e83-e88. doi: 10.3928/23258160-20180907-12. PMID: 30222824
Kuhli-Hattenbach C, Hofmann C, Wenner Y, Koch F, Kohnen T
J Cataract Refract Surg 2016 May;42(5):759-67. doi: 10.1016/j.jcrs.2016.02.040. PMID: 27255253
Mian M, Shah J, Dalpiaz A, Schwamb R, Miao Y, Warren K, Khan S
Fetal Pediatr Pathol 2015 Jun;34(3):169-75. Epub 2015 Jan 23 doi: 10.3109/15513815.2014.999394. PMID: 25616019
Gonzalez VH, Ober RR, Borchert MS, Bui KC, Ramos AD, Stout AU
Retina 1993;13(3):202-7. doi: 10.1097/00006982-199313030-00003. PMID: 8235100

Clinical prediction guides

Giorgio E, Vaula G, Bosco G, Giacone S, Mancini C, Calcia A, Cavalieri S, Di Gregorio E, Rigault De Longrais R, Leombruni S, Pinessi L, Cerrato P, Brusco A, Brussino A
J Neurol Sci 2015 May 15;352(1-2):99-104. Epub 2015 Apr 7 doi: 10.1016/j.jns.2015.03.042. PMID: 25873210

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