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Lethal congenital contracture syndrome 2(LCCS2)

MedGen UID:
334413
Concept ID:
C1843478
Disease or Syndrome
Synonyms: LCCS2; Lethal congenital contractural syndrome 2; Multiple contracture syndrome, Israeli Bedouin type; MULTIPLE CONTRACTURE SYNDROME, ISRAELI BEDOUIN TYPE A
SNOMED CT: Lethal congenital contracture syndrome type 2 (715419004); Multiple contracture syndrome Israeli-Bedouin type (715419004)
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): ERBB3 (12q13.2)
 
Monarch Initiative: MONDO:0011868
OMIM®: 607598
Orphanet: ORPHA137776

Definition

Lethal congenital contracture syndrome-2 (LCCS2) is an autosomal recessive disorder characterized by severe multiple congenital contractures with muscle wasting and atrophy. Micrognathia and other craniofacial anomalies, including cleft palate, as well as cardiac defects and enlarged urinary bladder at birth have also been reported. Hydrops fetalis and multiple pterygia are absent. Most patients have died in the neonatal period, although 2 survived to early adolescence (Landau et al., 2003). For a general phenotypic description and a discussion of genetic heterogeneity of LCCS, see LCCS1 (253310). [from OMIM]

Clinical features

From HPO
Hydronephrosis
MedGen UID:
42531
Concept ID:
C0020295
Disease or Syndrome
Severe distention of the kidney with dilation of the renal pelvis and calices.
Primary dilated cardiomyopathy
MedGen UID:
2880
Concept ID:
C0007193
Disease or Syndrome
Familial dilated cardiomyopathy is a genetic form of heart disease. It occurs when heart (cardiac) muscle becomes thin and weakened in at least one chamber of the heart, causing the open area of the chamber to become enlarged (dilated). As a result, the heart is unable to pump blood as efficiently as usual. To compensate, the heart attempts to increase the amount of blood being pumped through the heart, leading to further thinning and weakening of the cardiac muscle. Over time, this condition results in heart failure.\n\nIt usually takes many years for symptoms of familial dilated cardiomyopathy to cause health problems. They typically begin in mid-adulthood, but can occur at any time from infancy to late adulthood. Signs and symptoms of familial dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath (dyspnea), extreme tiredness (fatigue), fainting episodes (syncope), and swelling of the legs and feet. In some cases, the first sign of the disorder is sudden cardiac death. The severity of the condition varies among affected individuals, even in members of the same family.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Akinesia
MedGen UID:
43218
Concept ID:
C0085623
Finding
Inability to initiate changes in activity or movement and to perform ordinary volitional movements rapidly and easily.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Muscular atrophy
MedGen UID:
892680
Concept ID:
C0541794
Pathologic Function
The presence of skeletal muscular atrophy (which is also known as amyotrophy).
Arthrogryposis multiplex congenita
MedGen UID:
1830310
Concept ID:
C5779613
Disease or Syndrome
Multiple congenital contractures in different body areas.
Respiratory failure
MedGen UID:
257837
Concept ID:
C1145670
Disease or Syndrome
A severe form of respiratory insufficiency characterized by inadequate gas exchange such that the levels of oxygen or carbon dioxide cannot be maintained within normal limits.
Edema
MedGen UID:
4451
Concept ID:
C0013604
Pathologic Function
An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body.
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.
High myopia
MedGen UID:
78759
Concept ID:
C0271183
Disease or Syndrome
A severe form of myopia with greater than -6.00 diopters.
Degenerative vitreoretinopathy
MedGen UID:
334763
Concept ID:
C1843486
Disease or Syndrome

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVLethal congenital contracture syndrome 2
Follow this link to review classifications for Lethal congenital contracture syndrome 2 in Orphanet.

Recent clinical studies

Etiology

Oliwa A, Hendson G, Longman C, Synnes A, Seath K, Barnicoat A, Hall JG, Patel MS
Am J Med Genet A 2023 Feb;191(2):546-553. Epub 2022 Nov 1 doi: 10.1002/ajmg.a.63019. PMID: 36317804
Foo MXR, Ong PF, Dreesen O
J Dermatol Sci 2019 Nov;96(2):58-65. Epub 2019 Oct 22 doi: 10.1016/j.jdermsci.2019.10.003. PMID: 31727429
Leal GF, Nishimura G, Voss U, Bertola DR, Åström E, Svensson J, Yamamoto GL, Hammarsjö A, Horemuzova E, Papadiogannakis N, Iwarsson E, Grigelioniene G, Tham E
J Bone Miner Res 2018 Apr;33(4):753-760. Epub 2018 Jan 4 doi: 10.1002/jbmr.3348. PMID: 29178448
Rapin I
Handb Clin Neurol 2013;113:1637-50. doi: 10.1016/B978-0-444-59565-2.00032-0. PMID: 23622385
Superti-Furga A, Tenconi R, Clementi M, Eich G, Steinmann B, Boltshauser E, Giedion A
Am J Med Genet 1998 Jun 30;78(2):150-4. doi: 10.1002/(sici)1096-8628(19980630)78:2<150::aid-ajmg10>3.0.co;2-m. PMID: 9674906

Diagnosis

Foo MXR, Ong PF, Dreesen O
J Dermatol Sci 2019 Nov;96(2):58-65. Epub 2019 Oct 22 doi: 10.1016/j.jdermsci.2019.10.003. PMID: 31727429
Leal GF, Nishimura G, Voss U, Bertola DR, Åström E, Svensson J, Yamamoto GL, Hammarsjö A, Horemuzova E, Papadiogannakis N, Iwarsson E, Grigelioniene G, Tham E
J Bone Miner Res 2018 Apr;33(4):753-760. Epub 2018 Jan 4 doi: 10.1002/jbmr.3348. PMID: 29178448
Bend EG, Si Y, Stevenson DA, Bayrak-Toydemir P, Newcomb TM, Jorgensen EM, Swoboda KJ
Neurology 2016 Sep 13;87(11):1131-9. Epub 2016 Aug 24 doi: 10.1212/WNL.0000000000003095. PMID: 27558372Free PMC Article
Rapin I
Handb Clin Neurol 2013;113:1637-50. doi: 10.1016/B978-0-444-59565-2.00032-0. PMID: 23622385
Mau U, Kendziorra H, Kaiser P, Enders H
Am J Med Genet 1997 Aug 8;71(2):179-85. doi: 10.1002/(sici)1096-8628(19970808)71:2<179::aid-ajmg11>3.0.co;2-b. PMID: 9217218

Prognosis

Schorling DC, Rost S, Lefeber DJ, Brady L, Müller CR, Korinthenberg R, Tarnopolsky M, Bönnemann CG, Rodenburg RJ, Bugiani M, Beytia M, Krüger M, van der Knaap M, Kirschner J
Neurology 2017 Aug 15;89(7):657-664. Epub 2017 Jul 21 doi: 10.1212/WNL.0000000000004234. PMID: 28733338Free PMC Article
Bend EG, Si Y, Stevenson DA, Bayrak-Toydemir P, Newcomb TM, Jorgensen EM, Swoboda KJ
Neurology 2016 Sep 13;87(11):1131-9. Epub 2016 Aug 24 doi: 10.1212/WNL.0000000000003095. PMID: 27558372Free PMC Article
Michalk A, Stricker S, Becker J, Rupps R, Pantzar T, Miertus J, Botta G, Naretto VG, Janetzki C, Yaqoob N, Ott CE, Seelow D, Wieczorek D, Fiebig B, Wirth B, Hoopmann M, Walther M, Körber F, Blankenburg M, Mundlos S, Heller R, Hoffmann K
Am J Hum Genet 2008 Feb;82(2):464-76. doi: 10.1016/j.ajhg.2007.11.006. PMID: 18252226Free PMC Article
Superti-Furga A, Tenconi R, Clementi M, Eich G, Steinmann B, Boltshauser E, Giedion A
Am J Med Genet 1998 Jun 30;78(2):150-4. doi: 10.1002/(sici)1096-8628(19980630)78:2<150::aid-ajmg10>3.0.co;2-m. PMID: 9674906
Mau U, Kendziorra H, Kaiser P, Enders H
Am J Med Genet 1997 Aug 8;71(2):179-85. doi: 10.1002/(sici)1096-8628(19970808)71:2<179::aid-ajmg11>3.0.co;2-b. PMID: 9217218

Clinical prediction guides

Ekhilevitch N, Kurolap A, Oz-Levi D, Mory A, Hershkovitz T, Ast G, Mandel H, Baris HN
Clin Genet 2016 Jul;90(1):84-9. Epub 2016 Jan 20 doi: 10.1111/cge.12707. PMID: 26661508
Michalk A, Stricker S, Becker J, Rupps R, Pantzar T, Miertus J, Botta G, Naretto VG, Janetzki C, Yaqoob N, Ott CE, Seelow D, Wieczorek D, Fiebig B, Wirth B, Hoopmann M, Walther M, Körber F, Blankenburg M, Mundlos S, Heller R, Hoffmann K
Am J Hum Genet 2008 Feb;82(2):464-76. doi: 10.1016/j.ajhg.2007.11.006. PMID: 18252226Free PMC Article
Narkis G, Ofir R, Manor E, Landau D, Elbedour K, Birk OS
Am J Hum Genet 2007 Sep;81(3):589-95. Epub 2007 Jul 24 doi: 10.1086/520770. PMID: 17701904Free PMC Article
Superti-Furga A, Tenconi R, Clementi M, Eich G, Steinmann B, Boltshauser E, Giedion A
Am J Med Genet 1998 Jun 30;78(2):150-4. doi: 10.1002/(sici)1096-8628(19980630)78:2<150::aid-ajmg10>3.0.co;2-m. PMID: 9674906
Welsh KM, Smoller BR, Holbrook KA, Johnston K
Arch Dermatol 1992 Feb;128(2):228-31. doi: 10.1001/archderm.128.2.228. PMID: 1739302

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