Syndromes associated with deletion of the long arm of chromosome 18[del(18q)]

Mg, Wilson; Jw, Towner; Forsman, Irene; Siris, Evelyn

doi:10.1002/ajmg.1320030207

Cited by 102 publications

(96 citation statements)

References 19 publications

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“…Humans and mice with mutations in Sall1 (SALL1; TownesBrocks disorder) exhibit renal, ear, limb, anal, and cardiac abnormalities (21,25,42,53). Patients with 18q deletion syndrome, that encompasses the SALL3 locus among other genes (26) also exhibit ear, limb, and cardiac as well as face and palatal deficiencies (56). Many of these abnormalities are also found in patients with alterations in Shh signaling.…”

Section: Discussionmentioning

confidence: 99%

Loss of the Sall3 Gene Leads to Palate Deficiency, Abnormalities in Cranial Nerves, and Perinatal Lethality

Parrish

Ott

Lance‐Jones

et al. 2004

Molecular and Cellular Biology

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Members of the Spalt gene family encode putative transcription factors characterized by seven to nine C2H2 zinc finger motifs. Four genes have been identified in mice-Spalt1 to Spalt4 (Sall1 to Sall4). Spalt homologues are widely expressed in neural and mesodermal tissues during early embryogenesis. Sall3 is normally expressed in mice from embryonic day 7 (E7) in the neural ectoderm and primitive streak and subsequently in the brain, peripheral nerves, spinal cord, limb buds, palate, heart, and otic vesicles. We have generated a targeted disruption of Sall3 in mice. Homozygous mutant animals die on the first postnatal day and fail to feed. Examination of the oral structures of these animals revealed that abnormalities were present in the palate and epiglottis from E16.5. In E10.5 embryos, deficiencies in cranial nerves that normally innervate oral structures, particularly the glossopharyngeal nerve (IX), were observed. These studies indicate that Sall3 is required for the development of nerves that are derived from the hindbrain and for the formation of adjacent branchial arch derivatives.

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Section: Discussionmentioning

confidence: 99%

Loss of the Sall3 Gene Leads to Palate Deficiency, Abnormalities in Cranial Nerves, and Perinatal Lethality

Parrish

Ott

Lance‐Jones

et al. 2004

Molecular and Cellular Biology

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“…In addition, 12 cases of terminal or interstitial deletions of 18q specifically involving 18q21.2 have been described, although the inclusion of TCF4 in these deletions has not been confirmed. [15][16][17][18][19][20] Therefore, these cytogenetically described deletions were excluded from further comparison.…”

Section: Review Of Cases With Tcf4 Mutations or Deletions In The Litementioning

confidence: 99%

Genotype–phenotype analysis of TCF4 mutations causing Pitt-Hopkins syndrome shows increased seizure activity with missense mutations

Rosenfeld

Leppig

Ballif

et al. 2009

Genetics in Medicine

101

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Purpose: Pitt-Hopkins syndrome is characterized by severe mental retardation, characteristic dysmorphic features, and susceptibility to childhood-onset seizures and intermittent episodes of hyperventilation. This syndrome is caused by haploinsufficiency of TCF4, which encodes a basic helix-loop-helix transcription factor. Missense, nonsense, splicesite mutations, and gene deletions have been found in individuals with Pitt-Hopkins syndrome. Previous reports have suggested that the PittHopkins syndrome phenotype is independent of mutation or deletion type. Methods: We screened 13,186 individuals with microarray-based comparative genomic hybridization. We also conducted a review of the literature and statistical analysis of the phenotypic features for all individuals with confirmed mutations or deletions of TCF4. Results: We identified seven individuals with TCF4 deletions. All patients have features consistent with Pitt-Hopkins syndrome, although only three have breathing anomalies, and none has seizures. Our review of previously reported cases with TCF4 mutations and deletions showed that all patients with PittHopkins syndrome reported to date have severe psychomotor retardation, the onsets of seizures and hyperventilation episodes are limited to the first decade in most reported patients with Pitt-Hopkins syndrome, hyperventilation episodes are more common than seizures and are seen in the oldest patients, and individuals with missense TCF4 mutations are more likely to develop seizures. Conclusions: On the basis of an analysis of published cases, we propose a genotype-phenotype correlation of increased seizure activity with missense TCF4 mutations. itt-Hopkins syndrome (PTHS, OMIM 610954) was first described in 1978 1 in two individuals and is characterized by specific dysmorphic features (deep-set eyes, broad-beaked nose, wide mouth with bow-shaped upper lip, and widely spaced teeth), childhood-onset hyperventilation episodes, childhood-onset seizures, microcephaly, and severe psychomotor retardation with a happy disposition. It is an autosomal dominant condition caused by haploinsufficiency for TCF4 (transcription factor 4, OMIM 602272) on 18q21.2. [2][3][4] The etiology of PTHS was determined when two groups concurrently screened individuals with PTHS for chromosomal deletions using microarray technology, one with arraybased comparative genomic hybridization (aCGH) 5 and the other with single-nucleotide polymorphism-based molecular karyotyping. 3 Each group described a patient with a de novo deletion involving this gene. Further screening of individuals with PTHS or phenotypic overlap with PTHS found individuals with de novo missense and nonsense mutations in TCF4. 3,5 Subsequently, more individuals have been published with disruptions, deletions, and mutations in TCF4, most with typical PTHS features. 4,6 -10 TCF4 is a transcription factor that belongs to the class I basic helix-loop-helix (bHLH) protein family, also known as the "E-protein" family. These proteins form homo-and heterodimers with other heli...

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“…Mental retardation is found in case reports of all three abnormalities (18p-, 18q-, and 18p tetrasomy), and in one study was estimated at 68% of all 18q deletion subjects [Semrud-Clikeman et al, 2005]. Abnormal EEG findings and epilepsy have been described in case reports for all three chromosomal disorders [Chudley et al, 1974;Wilson et al, 1979;Wilson and Al Saadi, 1989;Schinzel et al, 1991;Chudley et al, 1992;Krasikov et al, 1992;Poissonnier et al, 1992;Engelen et al, 1998;Tinkle et al, 2003;Linnankivi et al, 2006;Swingle et al, 2006;Brenk et al, 2007;Cody et al, 2007]. Many subjects with 18p or 18q deletions display delayed speech, mutism, or articulation difficulties [Thompson et al, 1986;Poissonnier et al, 1992;Grosso et al, 1999;Babovic-Vuksanovic et al, 2004;Wester et al, 2006;Brenk et al, 2007;Cody et al, 2007] and there has been one report of short Neuropsychiatric Genetics attention span in three out of three 18p-subjects [Thompson et al, 1986].…”

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confidence: 93%

Psychiatric syndromes in individuals with chromosome 18 abnormalities

Zavala

Ramirez

Medina

et al. 2009

American J of Med Genetics Pt B

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Chromosome 18 abnormalities are associated with a range of physical abnormalities such as short stature and hearing impairments. Psychiatric manifestations have also been observed. This study focuses on the presentations of psychiatric syndromes as they relate to specific chromosomal abnormalities of chromosome 18. Twenty-five subjects (13 with an 18q deletion, 9 with 18p tetrasomy, and 3 with an 18p deletion), were interviewed by psychiatrists (blind to specific chromosomal abnormality) using the DIGS (subjects 18 and older) or KSADS-PL (subjects under 18). A consensus best estimation diagnostic process was employed to determine psychiatric syndromes. Oligonucleotide Array Comparative Genomic Hybridization (Agilent Technologies) was utilized to define specific regions of chromosome 18 that were deleted or duplicated. These data were further analyzed to determine critical regions of the chromosome as they relate to phenotypic manifestations in these subjects. 58.3% of the chromosome 18q- deletion subjects had depressive symptoms, 58.3% had anxiety symptoms, 25% had manic symptoms, and 25% had psychotic symptoms. 66.6% of the chromosome 18p- deletion subjects had anxiety symptoms, and none had depressive, manic, or psychotic symptoms. Fifty percent of the chromosome 18p tetrasomy subjects had anxiety symptoms, 12.5% had psychotic symptoms, and 12.5% had a mood disorder. All three chromosomal disorders were associated with high anxiety rates. Psychotic, manic and depressive disorders were seen mostly in 18q- subjects and this may be helpful in narrowing regions for candidate genes for these psychiatric conditions.

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Syndromes associated with deletion of the long arm of chromosome 18[del(18q)]

Cited by 102 publications

References 19 publications

Loss of the Sall3 Gene Leads to Palate Deficiency, Abnormalities in Cranial Nerves, and Perinatal Lethality

Loss of the Sall3 Gene Leads to Palate Deficiency, Abnormalities in Cranial Nerves, and Perinatal Lethality

Genotype–phenotype analysis of TCF4 mutations causing Pitt-Hopkins syndrome shows increased seizure activity with missense mutations

Psychiatric syndromes in individuals with chromosome 18 abnormalities

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