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Hydrolethalus syndrome 2(HLS2)

MedGen UID:
481529
Concept ID:
C3279899
Disease or Syndrome
Synonym: HLS2
 
Gene (location): KIF7 (15q26.1)
 
Monarch Initiative: MONDO:0013585
OMIM®: 614120

Definition

Hydrolethalus syndrome is an autosomal recessive embryonic lethal disorder characterized by hydrocephaly or anencephaly, postaxial polydactyly of the upper limbs, and pre- or postaxial polydactyly of the lower limbs. Duplication of the hallux is a common finding. HLS2 is considered a ciliopathy (summary by Putoux et al., 2011). Acrocallosal syndrome (ACLS; 200990) is an allelic disorder with a less severe phenotype. For a discussion of genetic heterogeneity of hydrolethalus syndrome, see 236680. [from OMIM]

Clinical features

From HPO
Postaxial hand polydactyly
MedGen UID:
609221
Concept ID:
C0431904
Congenital Abnormality
Supernumerary digits located at the ulnar side of the hand (that is, on the side with the fifth finger).
Postaxial foot polydactyly
MedGen UID:
384489
Concept ID:
C2112129
Finding
Polydactyly of the foot most commonly refers to the presence of six toes on one foot. Postaxial polydactyly affects the lateral ray and the duplication may range from a well-formed articulated digit to a rudimentary digit.
Preaxial foot polydactyly
MedGen UID:
389171
Concept ID:
C2112942
Finding
Duplication of all or part of the first ray.
Anencephaly
MedGen UID:
8068
Concept ID:
C0002902
Congenital Abnormality
Anencephaly is a condition that prevents the normal development of the brain and the bones of the skull. This condition results when a structure called the neural tube fails to close during the first few weeks of embryonic development. The neural tube is a layer of cells that ultimately develops into the brain and spinal cord. Because anencephaly is caused by abnormalities of the neural tube, it is classified as a neural tube defect.\n\nBecause the neural tube fails to close properly, the developing brain and spinal cord are exposed to the amniotic fluid that surrounds the fetus in the womb. This exposure causes the nervous system tissue to break down (degenerate). As a result, people with anencephaly are missing large parts of the brain called the cerebrum and cerebellum. These brain regions are necessary for thinking, hearing, vision, emotion, and coordinating movement. The bones of the skull are also missing or incompletely formed.\n\nBecause these nervous system abnormalities are so severe, almost all babies with anencephaly die before birth or within a few hours or days after birth.
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation.
Corpus callosum, agenesis of
MedGen UID:
104498
Concept ID:
C0175754
Congenital Abnormality
The corpus callosum is the largest fiber tract in the central nervous system and the major interhemispheric fiber bundle in the brain. Formation of the corpus callosum begins as early as 6 weeks' gestation, with the first fibers crossing the midline at 11 to 12 weeks' gestation, and completion of the basic shape by age 18 to 20 weeks (Schell-Apacik et al., 2008). Agenesis of the corpus callosum (ACC) is one of the most frequent malformations in brain with a reported incidence ranging between 0.5 and 70 in 10,000 births. ACC is a clinically and genetically heterogeneous condition, which can be observed either as an isolated condition or as a manifestation in the context of a congenital syndrome (see MOLECULAR GENETICS and Dobyns, 1996). Also see mirror movements-1 and/or agenesis of the corpus callosum (MRMV1; 157600). Schell-Apacik et al. (2008) noted that there is confusion in the literature regarding radiologic terminology concerning partial absence of the corpus callosum, where various designations have been used, including hypogenesis, hypoplasia, partial agenesis, or dysgenesis.
Molar tooth sign on MRI
MedGen UID:
400670
Concept ID:
C1865060
Finding
An abnormal appearance of the midbrain in axial magnetic resonance imaging in which the elongated superior cerebellar peduncles give the midbrain an appearance reminiscent of a molar or wisdom tooth.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).

Professional guidelines

PubMed

Chen CP, Chen CY, Chern SR, Su JW, Wang W
Taiwan J Obstet Gynecol 2012 Dec;51(4):643-8. doi: 10.1016/j.tjog.2012.10.001. PMID: 23276573

Recent clinical studies

Etiology

Shashi V, Clark P, Rogol AD, Wilson WG
Am J Med Genet 1995 May 22;57(1):22-6. doi: 10.1002/ajmg.1320570107. PMID: 7645593

Diagnosis

Ghesh L, Musquer MD, Devisme L, Stichelbout M, Boutaud L, Elkhartoufi N, Vaast P, Boute O, Riteau AS, Le Vaillant C, Winer N, Joubert M, Bezieau S, Thomas S, Attie-Bitach T, Beneteau C
Clin Genet 2021 Oct;100(4):462-467. Epub 2021 Jul 13 doi: 10.1111/cge.14021. PMID: 34212369
Oka M, Shimojima K, Yamamoto T, Hanaoka Y, Sato S, Yasuhara T, Yoshinaga H, Kobayashi K
Clin Genet 2016 Jun;89(6):739-43. Epub 2016 Mar 4 doi: 10.1111/cge.12752. PMID: 26830932
Chen CP, Chen CY, Chern SR, Su JW, Wang W
Taiwan J Obstet Gynecol 2012 Dec;51(4):643-8. doi: 10.1016/j.tjog.2012.10.001. PMID: 23276573
Chen CP
Taiwan J Obstet Gynecol 2007 Jun;46(2):111-20. doi: 10.1016/S1028-4559(07)60004-7. PMID: 17638618
Aughton DJ, Cassidy SB
Am J Med Genet 1987 Aug;27(4):935-42. doi: 10.1002/ajmg.1320270421. PMID: 3321994

Therapy

Shashi V, Clark P, Rogol AD, Wilson WG
Am J Med Genet 1995 May 22;57(1):22-6. doi: 10.1002/ajmg.1320570107. PMID: 7645593

Prognosis

Alby C, Piquand K, Huber C, Megarbané A, Ichkou A, Legendre M, Pelluard F, Encha-Ravazi F, Abi-Tayeh G, Bessières B, El Chehadeh-Djebbar S, Laurent N, Faivre L, Sztriha L, Zombor M, Szabó H, Failler M, Garfa-Traore M, Bole C, Nitschké P, Nizon M, Elkhartoufi N, Clerget-Darpoux F, Munnich A, Lyonnet S, Vekemans M, Saunier S, Cormier-Daire V, Attié-Bitach T, Thomas S
Am J Hum Genet 2015 Aug 6;97(2):311-8. Epub 2015 Jul 9 doi: 10.1016/j.ajhg.2015.06.003. PMID: 26166481Free PMC Article

Clinical prediction guides

Alby C, Piquand K, Huber C, Megarbané A, Ichkou A, Legendre M, Pelluard F, Encha-Ravazi F, Abi-Tayeh G, Bessières B, El Chehadeh-Djebbar S, Laurent N, Faivre L, Sztriha L, Zombor M, Szabó H, Failler M, Garfa-Traore M, Bole C, Nitschké P, Nizon M, Elkhartoufi N, Clerget-Darpoux F, Munnich A, Lyonnet S, Vekemans M, Saunier S, Cormier-Daire V, Attié-Bitach T, Thomas S
Am J Hum Genet 2015 Aug 6;97(2):311-8. Epub 2015 Jul 9 doi: 10.1016/j.ajhg.2015.06.003. PMID: 26166481Free PMC Article
Hingorani SR, Pagon RA, Shepard TH, Kapur RP
Am J Med Genet 1991 Nov 1;41(2):230-5. doi: 10.1002/ajmg.1320410220. PMID: 1785640

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