18q deletions: Clinical, molecular, and brain MRI findings of 14 individuals

Linnankivi, Tarja; Tienari, Pentti J.; Somer, Mirja; Kähkönen, Marketta; Lönnqvist, Tuula; Valanne, Leena; Pihko, Helena

doi:10.1002/ajmg.a.31072

Cited by 67 publications

(85 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Exceptions to this include Pelizaeus-Merzbacher disease 25,26 and chromosome 18q22.3-q23 deletions, 27 both of which may be associated with nystagmus. Nystagmus can be associated with various diseases, such as vestibular or cerebellar dysfunction or may be inherited, either as an isolated finding (congenital idiopathic/motor nystagmus) or related to sensory defects of the retina or anterior visual pathways, such as albinism or retinal dystrophy.…”

Section: Discussionmentioning

confidence: 99%

“…28 A single gene, FRMD7 at Xq26.2 (NYS1), has been identified as causing congenital nystagmus, [29][30][31] although other loci, including NYS5, NYS2 at 6p12, NYS3 at 7p11, NYS4 at 13q31-q33 and 18q exist. 27,[32][33][34][35][36] Detailed eye assessments of individuals from families 74, V and 683 demonstrated many common features, such as early age of onset of nystagmus, horizontal nystagmus present in all directions of gaze, pendular or increasing velocity waveforms, mildly reduced VA and absence of sensory defects. The consistent finding of gaze-evoked nystagmus indicates a dysfunction of the neural integrator, which is required for all conjugate eye movements.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

CASK mutations are frequent in males and cause X-linked nystagmus and variable XLMR phenotypes

et al. 2009

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CASK mutations are frequent in males and cause X-linked nystagmus and variable XLMR phenotypes

et al. 2009

View full text Add to dashboard Cite

“…Autoimmune disease and low levels of Immunoglobulin A have been reported in some cases of the 18q-syndrome [9]. Distal 18q-is involved in neural development [10]. This is the first patient reported to have this chromosomal deletion in addition to very high levels of IgE and severe atopic dermatitis.…”

Section: Discussionmentioning

confidence: 78%

Is It Hyper IgE Syndrome Or Something Else?

Yasharpour

2014

MOJI

View full text Add to dashboard Cite

Submit Manuscript | http://medcraveonline.com MOJ Immunologytesting was significantly positive for Bermuda grass, cat dander, dog dander, house dust, egg white, and egg yolk. Stool ova and parasites were negative in addition to specific IgE to anisakis and IgG to strongyloides. Levels of IgA were 284 mg/dl, IgG 1720mg/ dl, IgM 63 mg/dl.B cell subsets were also evaluated. Marginal zone B and class switch memory B cells are low. Transitional B cells and CD21 low are high. The other subsets were within the normal range. What is the differential diagnosis of an elevated IgE level?The differential diagnosis of elevated IgE level is extensive. In this discussion we will include those causes that can be associated with levels greater than 5000 IU/ml (Table 1). Inflammatory Causes Kimura diseaseKimura disease is a rare, benign inflammatory disease most frequently affecting Asian men in the third decade of life. Presenting symptoms include regional lymphadenopathy and adenitis of the face and neck. Laboratory studies reveal peripheral eosinophilia, and elevated total IgE levels reported in case reports as greater than 5,000 IU/ml [1]. Churg-Strauss syndromeChurg-Strauss syndrome features extravascular granulomatosis, eosinophilic vasculitis of small and mediumsized vessels, severe peripheral eosinophilia, and elevated IgE levels usually up to 5,000 IU/ml [2]. Allergic Causes Atopic dermatitisIn atopic dermatitis, IgE levels may be elevated, even to more than 10,000 IU/mL. There is increased susceptibility to cutaneous infections, but more invasive infections should prompt an evaluation for immunodeficiency. Importantly, the IgE level in patients with atopic dermatitis has reactivity to a broad range of food and inhalant allergens [3]. Case Presentation Chief complaintPersistently elevated IgE level in a patient with atopic dermatitis History of present illnessOur patient is a 39 year old male who was referred to our clinic for evaluation of an extremely elevated IgE level. He had been followed by an outside allergist for severe atopic dermatitis, asthma and upon their evaluation was found to have extremely elevated levels of IgE, beyond the level expected in a patient with atopic dermatitis. He complained of nasal congestion, itching and sneezing. There was no history of recurrent staphylococcal skin or pulmonary infections. In addition, he did not have a history of viral diseases or prolonged illness. Medical historyReview of our patient's history revealed that he had bilateral foot surgery as a child and hearing loss since the age of ten. He also has developmental delay and mental retardation. Physical examinationPhysical examination was notable for a diffuse eczematoid skin rash, complicated by excoriation and lichenification especially on his upper and lower extremities, face, and groin. In addition he had dysmorphic facial features, proximal thumbs, and single palmar creases. He did not have coarse facies, scoliosis or delayed shedding of the primary teeth. Family historyHe has a sister with historical cat allergy, ...

show abstract

“…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

View full text Add to dashboard Cite

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...

show abstract

18q deletions: Clinical, molecular, and brain MRI findings of 14 individuals

Cited by 67 publications

References 25 publications

CASK mutations are frequent in males and cause X-linked nystagmus and variable XLMR phenotypes

CASK mutations are frequent in males and cause X-linked nystagmus and variable XLMR phenotypes

Is It Hyper IgE Syndrome Or Something Else?

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

Contact Info

Product

Resources

About