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Semilobar holoprosencephaly

MedGen UID:
199694
Concept ID:
C0751617
Congenital Abnormality
Synonyms: Holoprosencephalies, Semilobar; Holoprosencephaly, Semilobar; Semilobar Holoprosencephalies; Semilobar Holoprosencephaly
SNOMED CT: Semi-lobar holoprosencephaly (253138008)
Modes of inheritance:
Non-Mendelian inheritance
MedGen UID:
109109
Concept ID:
C0600599
Genetic Function
Source: Orphanet
A mode of inheritance that depends on genetic determinants in more than one gene.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
HPO: HP:0002507
Orphanet: ORPHA220386

Definition

A type of holoprosencephaly in which the left and right frontal and parietal lobes are fused and the interhemispheric fissure is only present posteriorly. [from HPO]

Term Hierarchy

Conditions with this feature

Holoprosencephaly-craniosynostosis syndrome
MedGen UID:
330464
Concept ID:
C1832424
Disease or Syndrome
Holoprosencephaly-craniosynostosis syndrome is a rare developmental defect during embryogenesis syndrome characterized by the association of primary craniosynostosis (usually involving the coronal and metopic sutures) with holoprosencephaly (ranging from alobar to, most commonly, semilobar) and various skeletal anomalies (typically, hand and feet anomalies including fifth digit clinodactyly, hypoplastic phalanges and cone-shaped epiphyses, small vertebral bodies, scoliosis, coxa valga and/or flexion deformities of hips). Craniofacial asymmetry, microcephaly, brachy/plagiocephaly, short stature and psychomotor delay are additional common features.
Holoprosencephaly 2
MedGen UID:
322517
Concept ID:
C1834877
Disease or Syndrome
A rare disorder characterized by the partial separation of the cerebral hemispheres. It is associated with mutations in the SIX3 gene.
Holoprosencephaly 7
MedGen UID:
372134
Concept ID:
C1835820
Disease or Syndrome
Holoprosencephaly (HPE) is the most commonly occurring congenital structural forebrain anomaly in humans. HPE is associated with mental retardation and craniofacial malformations. Considerable heterogeneity in the genetic causes of HPE has been demonstrated (Ming et al., 2002). For general phenotypic information and a discussion of genetic heterogeneity of holoprosencephaly, see HPE1 (236100).
Holoprosencephaly 4
MedGen UID:
374488
Concept ID:
C1840528
Disease or Syndrome
A rare disorder caused by mutations in the TGIF gene mapped to chromosome 18p11.3. It is characterized by semilobar holoprosencephaly, hypotelorism, and ptosis.
Hartsfield-Bixler-Demyer syndrome
MedGen UID:
335111
Concept ID:
C1845146
Congenital Abnormality
FGFR1-related Hartsfield syndrome comprises two core features: holoprosencephaly (HPE) spectrum disorder and ectrodactyly spectrum disorder. HPE spectrum disorder, resulting from failed or incomplete forebrain division early in gestation, includes alobar, semilobar, or lobar HPE. Other observed midline brain malformations include corpus callosum agenesis, absent septum pellucidum, absent olfactory bulbs and tracts, and vermian hypoplasia. Other findings associated with the HPE spectrum such as craniofacial dysmorphism, neurologic issues (developmental delay, spasticity, seizures, hypothalamic dysfunction), feeding problems, and endocrine issues (hypogonadotropic hypogonadism and central insipidus diabetes) are common. Ectrodactyly spectrum disorders are unilateral or bilateral malformations of the hands and/or feet characterized by a median cleft of hand or foot due to absence of the longitudinal central rays (also called split-hand/foot malformation). The number of digits on the right and left can vary. Polydactyly and syndactyly can also be seen.
Ectrodactyly, ectodermal dysplasia, and cleft lip-palate syndrome 1
MedGen UID:
343663
Concept ID:
C1851841
Disease or Syndrome
An EEC syndrome characterized by autosomal dominant inheritance that has material basis in variation in the chromosome region 7q11.2-q21.3.
Lambotte syndrome
MedGen UID:
343380
Concept ID:
C1855550
Disease or Syndrome
Holoprosencephaly 5
MedGen UID:
355304
Concept ID:
C1864827
Disease or Syndrome
Holoprosencephaly associated with mutations in the ZIC2 gene.
Holoprosencephaly 12 with or without pancreatic agenesis
MedGen UID:
1684550
Concept ID:
C5193131
Disease or Syndrome
Holoprosencephaly-12 with or without pancreatic agenesis (HPE12) is a developmental disorder characterized by abnormal separation of the embryonic forebrain (HPE) resulting in dysmorphic facial features and often, but not always, impaired neurologic development. Most patients with this form of HPE also have congenital absence of the pancreas, resulting in early-onset type 1 diabetes mellitus and requiring pancreatic enzyme replacement. Other features may include hearing loss and absence of the gallbladder (summary by De Franco et al., 2019 and Kruszka et al., 2019). For a phenotypic description and a discussion of genetic heterogeneity of holoprosencephaly, see HPE1 (236100).
Neurodevelopmental disorder with spastic quadriplegia, optic atrophy, seizures, and structural brain anomalies
MedGen UID:
1684884
Concept ID:
C5231442
Disease or Syndrome
Halperin-Birk syndrome (HLBKS) is an autosomal recessive neurodevelopmental disorder characterized by structural brain defects, spastic quadriplegia with multiple contractures, profound developmental delay, seizures, dysmorphism, cataract, and optic nerve atrophy. Death occurs in early childhood (Halperin et al., 2019).
Holoprosencephaly 13, X-linked
MedGen UID:
1714826
Concept ID:
C5393308
Disease or Syndrome
X-linked holoprosencephaly-13 (HPE13) is a neurologic disorder characterized by midline developmental defects that mainly affect the brain and craniofacial structure. The severity and manifestations are variable: some patients may have full alobar HPE with cyclopia, whereas others have semilobar HPE or septooptic dysplasia. Dysmorphic features include microcephaly, hypotelorism, low-set ears, micrognathia, and cleft lip/palate. Patients with a more severe phenotype may die in the newborn period, whereas those with a less severe phenotype show global developmental delay. Additional variable features include congenital heart defects and vertebral anomalies. Phenotypic variability may be related to the type of mutation, X-inactivation status, and possible incomplete penetrance. The STAG2 protein is part of the multiprotein cohesin complex involved in chromatid cohesion during DNA replication and transcriptional regulation; HPE13 can thus be classified as a 'cohesinopathy' (summary by Kruszka et al., 2019). For a discussion of genetic heterogeneity of holoprosencephaly, see HPE1 (236100).
Developmental and epileptic encephalopathy, 85, with or without midline brain defects
MedGen UID:
1708832
Concept ID:
C5393312
Disease or Syndrome
Developmental and epileptic encephalopathy-85 with or without midline brain defects (DEE85) is an X-linked neurologic disorder characterized by onset of severe refractory seizures in the first year of life, global developmental delay with impaired intellectual development and poor or absent speech, and dysmorphic facial features. The seizures tend to show a cyclic pattern with clustering. Many patients have midline brain defects on brain imaging, including thin corpus callosum and/or variable forms of holoprosencephaly (HPE). The severity and clinical manifestations are variable. Almost all reported patients are females with de novo mutations predicted to result in a loss of function (LOF). However, some patients may show skewed X inactivation, and the pathogenic mechanism may be due to a dominant-negative effect. The SMC1A protein is part of the multiprotein cohesin complex involved in chromatid cohesion during DNA replication and transcriptional regulation; DEE85 can thus be classified as a 'cohesinopathy' (summary by Symonds et al., 2017 and Kruszka et al., 2019). For a general phenotypic description and a discussion of genetic heterogeneity of DEE, see 308350.

Professional guidelines

PubMed

Mandel AM
Handb Clin Neurol 2020;171:291-311. doi: 10.1016/B978-0-444-64239-4.00015-1. PMID: 32736756
Kousa YA, du Plessis AJ, Vezina G
Am J Med Genet C Semin Med Genet 2018 Jun;178(2):206-213. Epub 2018 May 17 doi: 10.1002/ajmg.c.31618. PMID: 29770996
Voutetakis A, Sertedaki A, Dacou-Voutetakis C
Curr Opin Pediatr 2016 Aug;28(4):545-50. doi: 10.1097/MOP.0000000000000378. PMID: 27386973

Recent clinical studies

Etiology

Hu Y, Sun L, Feng L, Wang J, Zhu Y, Wu Q
BMC Pregnancy Childbirth 2023 May 3;23(1):312. doi: 10.1186/s12884-023-05644-z. PMID: 37138220Free PMC Article
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Am J Med Genet A 2019 Nov;179(11):2170-2177. Epub 2019 Jul 28 doi: 10.1002/ajmg.a.61305. PMID: 31353810
Pallangyo P, Lyimo F, Nicholaus P, Makungu H, Mtolera M, Mawenya I
J Med Case Rep 2016 Dec 20;10(1):358. doi: 10.1186/s13256-016-1141-y. PMID: 27998308Free PMC Article
Yang MT, Lee WT, Peng SS, Lin HC, Tseng CL, Liang JS, Wang PJ, Shen YZ
Epileptic Disord 2004 Sep;6(3):173-80. PMID: 15504716
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Diagnosis

Schlosser AS, Costa GJC, Silva HSD, Mello JLM, Gomes LO, Onoyama MMO, Costa TMC
Rev Paul Pediatr 2023;41:e2022027. Epub 2023 Mar 13 doi: 10.1590/1984-0462/2023/41/2022027. PMID: 36921175Free PMC Article
Hilbrands R, Keymolen K, Michotte A, Marichal M, Cools F, Goossens A, Veld PI, De Schepper J, Hattersley A, Heimberg H
BMC Med Genet 2017 May 19;18(1):57. doi: 10.1186/s12881-017-0419-2. PMID: 28525974Free PMC Article
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McGahan JP, Nyberg DA, Mack LA
AJR Am J Roentgenol 1990 Jan;154(1):143-8. doi: 10.2214/ajr.154.1.2104699. PMID: 2104699

Therapy

Djermane A, Elmaleh M, Simon D, Poidvin A, Carel JC, Léger J
J Clin Endocrinol Metab 2016 Feb;101(2):635-43. Epub 2015 Nov 20 doi: 10.1210/jc.2015-3108. PMID: 26588450
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Pediatr Endocrinol Rev 2011 Sep;9(1):476-8. PMID: 22783645
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Prognosis

Schlosser AS, Costa GJC, Silva HSD, Mello JLM, Gomes LO, Onoyama MMO, Costa TMC
Rev Paul Pediatr 2023;41:e2022027. Epub 2023 Mar 13 doi: 10.1590/1984-0462/2023/41/2022027. PMID: 36921175Free PMC Article
Kruszka P, Berger SI, Weiss K, Everson JL, Martinez AF, Hong S, Anyane-Yeboa K, Lipinski RJ, Muenke M
Am J Hum Genet 2019 May 2;104(5):990-993. Epub 2019 Apr 18 doi: 10.1016/j.ajhg.2019.03.017. PMID: 31006510Free PMC Article
Essa AA, Feleke LA, Ahmed DM
J Med Case Rep 2018 Jul 7;12(1):207. doi: 10.1186/s13256-018-1647-6. PMID: 29980223Free PMC Article
Mallick S, Panda SS, Ray R, Shukla R, Kabra M, Agarwal R
BMJ Case Rep 2014 Mar 13;2014 doi: 10.1136/bcr-2014-203597. PMID: 24626384Free PMC Article
Martínez-Frías ML, Egüés X, Puras A, Hualde J, de Frutos CA, Bermejo E, Nieto MA, Martínez S
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Clinical prediction guides

Kruszka P, Berger SI, Weiss K, Everson JL, Martinez AF, Hong S, Anyane-Yeboa K, Lipinski RJ, Muenke M
Am J Hum Genet 2019 May 2;104(5):990-993. Epub 2019 Apr 18 doi: 10.1016/j.ajhg.2019.03.017. PMID: 31006510Free PMC Article
Pallangyo P, Lyimo F, Nicholaus P, Makungu H, Mtolera M, Mawenya I
J Med Case Rep 2016 Dec 20;10(1):358. doi: 10.1186/s13256-016-1141-y. PMID: 27998308Free PMC Article
Martínez-Frías ML, Egüés X, Puras A, Hualde J, de Frutos CA, Bermejo E, Nieto MA, Martínez S
Am J Med Genet A 2011 Jan;155A(1):197-202. doi: 10.1002/ajmg.a.33765. PMID: 21204232
Yang MT, Lee WT, Peng SS, Lin HC, Tseng CL, Liang JS, Wang PJ, Shen YZ
Epileptic Disord 2004 Sep;6(3):173-80. PMID: 15504716
Judas M, Rasin MR, Kruslin B, Kostović K, Jukić D, Petanjek Z, Kostović I
Brain Dev 2003 Jan;25(1):32-9. doi: 10.1016/s0387-7604(02)00149-3. PMID: 12536031

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