Cytogenetics and holoprosencephaly: A chromosomal microarray study of 222 individuals with holoprosencephaly

Hu, Tommy; Kruszka, Paul; Martinez, Ariel F.; Ming, Jeffrey E.; Shabason, Emily K.; Raam, Manu S.; Shaikh, Tamim H.; Pineda-Álvarez, Daniel E.; Muenke, Maximilian

doi:10.1002/ajmg.c.31622

Cited by 6 publications

(6 citation statements)

References 59 publications

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“…These include chromosomal abnormalities (e.g., trisomy 13 and trisomy 18), chromosomal rearrangements, copy number variations, or gene mutations. The gene mutations are typically in one of the four major HPE causative genes, namely SHH , ZIC2 , SIX3 , and TGIF1 , although other candidate genes have been proposed . In our survey, all chromosomal abnormalities were related to Chromosome 7, 13, or 18.…”

Section: Discussionmentioning

confidence: 82%

Nationwide epidemiological survey of holoprosencephaly in Japan

Abe

Araki

Sobajima

et al. 2020

Pediatrics International

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Background: Holoprosencephaly (HPE) is a congenital malformation with an estimated prevalence of 0.10-6.06 per 10 000 births but with no nationwide data specific to Japan. Methods: This nationwide retrospective questionnaire survey was conducted from 2011 to 2013. All 467 training hospitals for perinatal and neonatal care certified by the Japan Society of Perinatal and Neonatal Medicine were contacted. The birth prevalence rate (BPR) was assessed from the primary survey and clinical characteristics from the secondary survey. Results: We received valid responses from 253 hospitals in the primary survey (54.6%). Of 390 342 live births, 60 were diagnosed with HPE (23 males and 37 females), resulting in an actual BPR of 1.54 per 10 000 live births. The point estimate for HPE cases was 100 (95% confidence interval [CI]: 80.7-120), and the estimated BPR of HPE was calculated to be 0.32 per 10 000 live births (95% CI: 0.26-0.38) based on 3 117 853 live births according to Japanese national statistics during the study period. In the secondary survey, we obtained data for 49 cases (19 males and 30 females). Of these, 20 were alobar (40.8%), 20 were semilobar (40.8%), five were lobar (10.4%), and four were of unknown type. Genetic examination was performed in 37 of the 49 HPE patients and revealed that chromosomes 13, 18, and 7 were affected in eight, six, and four patients, respectively. Conclusions: This is the most extensive survey on holoprosencephaly to date in Japan. The estimated BPR was consistent with that reported in previous research.

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Section: Discussionmentioning

confidence: 82%

Nationwide epidemiological survey of holoprosencephaly in Japan

Abe

Araki

Sobajima

et al. 2020

Pediatrics International

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“…Deletions or duplications involving various regions of 13q, and del (18p), del (7) (q36), dup (3) (p24-pter), del (2) (p21), and del (21) (q22.3) have been frequently reported. 10,51…”

Section: Chromosomal Abnormalitiesmentioning

confidence: 99%

Holoprosencephaly

Huisman,

Huisman

2024

Newborn

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Holoprosencephaly (HPE) is a complex malformation of the forebrain resulting from failed or incomplete division of the forebrain during the embryonic period. It is the most frequently seen developmental abnormality of the forebrain in humans; the incidence is nearly 1 of every 250 human embryos. However, most of these embryos do not survive and are lost to miscarriage. At birth, the prevalence is 1 in 8,000-10,000 live births and stillbirths. In HPE, the cleavage of the forebrain (prosencephalon) into the right and left hemispheres, deep brain structures, and the olfactory and optic bulbs and tracts remains incomplete. These central nervous system (CNS) defects develop during the first few 2-3 weeks of the fetal period. The etiopathogenesis is unclear, although both syndromic and isolated HPE can be heritable. The condition involves multiple systems, including the central nervous system, eyes, hearing, olfactory, gastrointestinal system, and genital tracts can be most severely affected. No specific treatment is known. Careful clinical and genetic evaluation is necessary for symptomatic management and for counseling families. In this article, we present our own clinical and imaging experience and combine it with an extensive search in the databases PubMed, EMBASE, and Scopus. To avoid bias, keywords were identified from discussions in our own group and from PubMed's Medical Subject Heading (MeSH) thesaurus.

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“…Pathogenic structural chromosome abnormalities, i.e., copy number variants (CNVs), are found in 10–14% of individuals with HPE [ 6 , 52 , 54 ]. Though they have been reported in virtually all chromosomes, causal structural chromosomal anomalies frequently involve regions harboring known HPE genes.…”

Section: Etiologymentioning

confidence: 99%

“…Though they have been reported in virtually all chromosomes, causal structural chromosomal anomalies frequently involve regions harboring known HPE genes. For example, CNVs involving chromosome 18p11.3, which include TGIF1 , a HPE gene, have been reported in many patients [ 54 ]. Similarly, recurrent CNVs in 2p21, which includes SIX3 , have been published [ 54 ].…”

Section: Etiologymentioning

confidence: 99%

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Holoprosencephaly: Review of Embryology, Clinical Phenotypes, Etiology and Management

et al. 2023

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Holoprosencephaly (HPE) is the most common malformation of the prosencephalon in humans. It is characterized by a continuum of structural brain anomalies resulting from the failure of midline cleavage of the prosencephalon. The three classic subtypes of HPE are alobar, semilobar and lobar, although a few additional categories have been added to this original classification. The severity of the clinical phenotype is broad and usually mirrors the radiologic and associated facial features. The etiology of HPE includes both environmental and genetic factors. Disruption of sonic hedgehog (SHH) signaling is the main pathophysiologic mechanism underlying HPE. Aneuploidies, chromosomal copy number variants and monogenic disorders are identified in a large proportion of HPE patients. Despite the high postnatal mortality and the invariable presence of developmental delay, recent advances in diagnostic methods and improvements in patient management over the years have helped to increase survival rates. In this review, we provide an overview of the current knowledge related to HPE, and discuss the classification, clinical features, genetic and environmental etiologies and management.

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Cytogenetics and holoprosencephaly: A chromosomal microarray study of 222 individuals with holoprosencephaly

Cited by 6 publications

References 59 publications

Nationwide epidemiological survey of holoprosencephaly in Japan

Nationwide epidemiological survey of holoprosencephaly in Japan

Holoprosencephaly

Holoprosencephaly: Review of Embryology, Clinical Phenotypes, Etiology and Management

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