Tatton-Brown–Rahman syndrome: Difference between revisions
Aeffenberger (talk | contribs) ←Created page with '{{Short description|Overgrowth syndrome caused by DNMT3A gene mutation}} {{Infobox medical condition | name = {{PAGENAME}} | synonym = DNMT3A overgrowth syndrome | image = | width = | alt = | caption = | pronounce = | field = Medical genetics | symptoms = Intellectual disability, overgrowth, facial dysmorphisms | onset = Present at birth | duration = |...' |
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== Signs and symptoms == |
== Signs and symptoms == |
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TBRS is defined by overgrowth and mild-to-severe [[intellectual disability]]. All individuals with TBRS experience some degree of developmental delay and/or intellectual disability, with 86% of well-documented cases falling in the mild to moderate range. Most individuals with TBRS exhibit [[Human height|stature]], [[Macrocephaly|head circumference]], and [[Overweight|weight]] at least two standard deviations above the mean.<ref name="generev"/> |
TBRS is defined by overgrowth and mild-to-severe [[intellectual disability]]. All individuals with TBRS experience some degree of developmental delay and/or intellectual disability, with 86% of well-documented cases falling in the mild to moderate range. Most individuals with TBRS exhibit increased [[Human height|stature]], [[Macrocephaly|head circumference]], and [[Overweight|weight]] at least two standard deviations above the mean.<ref name="generev"/> |
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Generalized [[Hypermobility (joints)|joint hypermobility]] and [[hypotonia]] are observed in ~75% and ~55% of cases, respectively, and are often associated with musculoskeletal pain and joint instability. Approximately half of individuals exhibit behavioral or psychiatric issues; the most common diagnosis is [[autism spectrum]] disorder.<ref name="pmid29900417"/> [[Febrile seizure]]s and afebrile [[seizure]]s have been reported in ~20% of individuals with TBRS.<ref name="generev"/> |
Generalized [[Hypermobility (joints)|joint hypermobility]] and [[hypotonia]] are observed in ~75% and ~55% of cases, respectively, and are often associated with musculoskeletal pain and joint instability. Approximately half of individuals exhibit behavioral or psychiatric issues; the most common diagnosis is [[autism spectrum]] disorder.<ref name="pmid29900417"/> [[Febrile seizure]]s and afebrile [[seizure]]s have been reported in ~20% of individuals with TBRS.<ref name="generev"/> |
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The facial gestalt of TBRS includes a round face; thick, horizontal, low-set eyebrows; vertically narrow [[palpebral fissure]]s; and prominent [[maxillary central incisor]]s. These often become most clinically recognizable in adolescence.<ref name="pmid29900417"/> |
The facial gestalt of TBRS includes a round face; thick, horizontal, low-set eyebrows; vertically narrow [[palpebral fissure]]s; and prominent [[maxillary central incisor]]s. These features often become most clinically recognizable in adolescence.<ref name="pmid29900417"/> |
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[[Congenital heart defect]]s and [[Aneurysm of sinus of Valsalva|aortic root dilatation]] have been observed in ~10% of cases. Approximately 20% of males with TBRS have [[cryptorchidism]]. [[Vesicoureteral reflux]] and [[hypospadias]] have been reported in some cases.<ref name="generev"/> |
[[Congenital heart defect]]s and [[Aneurysm of sinus of Valsalva|aortic root dilatation]] have been observed in ~10% of cases. Approximately 20% of males with TBRS have [[cryptorchidism]]. [[Vesicoureteral reflux]] and [[hypospadias]] have been reported in some cases.<ref name="generev"/> |
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<ref name="pmid29900417">{{cite journal| author=Tatton-Brown K, Zachariou A, Loveday C, Renwick A, Mahamdallie S | display-authors=etal| title=The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with de novo constitutive DNMT3A variants. | journal=Wellcome Open Res | year= 2018 | volume= 3 | issue= | pages= 46 | pmid=29900417 | doi=10.12688/wellcomeopenres.14430.1 | pmc=5964628}}</ref> |
<ref name="pmid29900417">{{cite journal| author=Tatton-Brown K, Zachariou A, Loveday C, Renwick A, Mahamdallie S | display-authors=etal| title=The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with de novo constitutive DNMT3A variants. | journal=Wellcome Open Res | year= 2018 | volume= 3 | issue= | pages= 46 | pmid=29900417 | doi=10.12688/wellcomeopenres.14430.1 | pmc=5964628}}</ref> |
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<ref name="pmid37795572">{{cite journal| author=Jiménez de la Peña M, Rincón-Pérez I, López-Martín S, Albert J, Martín Fernández-Mayoralas D, Fernández-Perrone AL | display-authors=etal| title=Tatton-Brown-Rahman syndrome: Novel pathogenic variants and new neuroimaging findings. | journal=Am J Med Genet A | year= 2023 | volume= | issue= | pages= | pmid=37795572 | doi=10.1002/ajmg.a.63434}}</ref> |
<ref name="pmid37795572">{{cite journal| author=Jiménez de la Peña M, Rincón-Pérez I, López-Martín S, Albert J, Martín Fernández-Mayoralas D, Fernández-Perrone AL | display-authors=etal| title=Tatton-Brown-Rahman syndrome: Novel pathogenic variants and new neuroimaging findings. | journal=Am J Med Genet A | year= 2023 | volume= | issue= | pages= | pmid=37795572 | doi=10.1002/ajmg.a.63434 |doi-access=free}}</ref> |
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<ref name="pmid37098340">{{cite journal| author=Hamagami N, Wu DY, Clemens AW, Nettles SA, Li A, Gabel HW | title=NSD1 deposits histone H3 lysine 36 dimethylation to pattern non-CG DNA methylation in neurons. | journal=Mol Cell | year= 2023 | volume= 83 | issue= 9 | pages= 1412-1428.e7 | pmid=37098340 | doi=10.1016/j.molcel.2023.04.001 | pmc=10230755}}</ref> |
<ref name="pmid37098340">{{cite journal| author=Hamagami N, Wu DY, Clemens AW, Nettles SA, Li A, Gabel HW | title=NSD1 deposits histone H3 lysine 36 dimethylation to pattern non-CG DNA methylation in neurons. | journal=Mol Cell | year= 2023 | volume= 83 | issue= 9 | pages= 1412-1428.e7 | pmid=37098340 | doi=10.1016/j.molcel.2023.04.001 | pmc=10230755}}</ref> |
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Revision as of 01:25, 10 January 2024
| Tatton-Brown–Rahman syndrome | |
|---|---|
| Other names | DNMT3A overgrowth syndrome |
| Specialty | Medical genetics |
| Symptoms | Intellectual disability, overgrowth, facial dysmorphisms |
| Usual onset | Present at birth |
| Causes | DNMT3A mutation |
| Diagnostic method | Molecular genetic testing |
| Differential diagnosis | Cohen–Gibson syndrome, Fragile X syndrome, Malan syndrome, Simpson–Golabi–Behmel syndrome, Sotos syndrome, Weaver syndrome |
| Treatment | Based on symptoms |
| Frequency | 90 reported cases[1] |
| Named after | Nazneen Rahman |
Tatton-Brown–Rahman syndrome (TBRS) is a rare overgrowth and intellectual disability syndrome caused by autosomal dominant mutations in the DNMT3A gene.[1] The syndrome was first recognized in 2014 by Katrina Tatton-Brown, Nazneen Rahman, and collaborators.[2]
Signs and symptoms
TBRS is defined by overgrowth and mild-to-severe intellectual disability. All individuals with TBRS experience some degree of developmental delay and/or intellectual disability, with 86% of well-documented cases falling in the mild to moderate range. Most individuals with TBRS exhibit increased stature, head circumference, and weight at least two standard deviations above the mean.[1]
Generalized joint hypermobility and hypotonia are observed in ~75% and ~55% of cases, respectively, and are often associated with musculoskeletal pain and joint instability. Approximately half of individuals exhibit behavioral or psychiatric issues; the most common diagnosis is autism spectrum disorder.[3] Febrile seizures and afebrile seizures have been reported in ~20% of individuals with TBRS.[1]
The facial gestalt of TBRS includes a round face; thick, horizontal, low-set eyebrows; vertically narrow palpebral fissures; and prominent maxillary central incisors. These features often become most clinically recognizable in adolescence.[3]
Congenital heart defects and aortic root dilatation have been observed in ~10% of cases. Approximately 20% of males with TBRS have cryptorchidism. Vesicoureteral reflux and hypospadias have been reported in some cases.[1]
Neuroimaging findings may include corpus callosum anomalies, small posterior cranial fossa, asymmetric arcuate and uncinate fasciculi, deep left Sylvian fissure, and increased cortical thickness[4]
Cause
TBRS is caused by autosomal dominant mutations in the DNMT3A gene. Nearly all cases are caused by de novo mutations; rarely, a pathogenic variant can be inherited from an affected parent or an unaffected mosaic parent.[1] DNMT3A overgrowth mutations are hypothesized to interfere with the enzyme's role in H3K36me2-regulated non-CpG DNA methylation activity.[2][5]
Management and prognosis
The majority of individuals with TBRS are in good health. An individual's specific features are treated and managed as indicated. Early childhood intervention and special education (ISFP and IEP in the United States) are recommended.
Because DNMT3A mutations are commonly observed in acute myeloid leukemia, TBRS may be associated with increased cancer risk.[2]
See also
References
- ^ a b c d e f Ostrowski PJ, Tatton-Brown K (2022-06-30). Adam MP, Feldman J, Mirzaa GM; et al. (eds.). "Tatton-Brown-Rahman Syndrome". GeneReviews. Retrieved 2024-01-09.
{{cite web}}: CS1 maint: multiple names: editors list (link) - ^ a b c Tatton-Brown K, Seal S, Ruark E, Harmer J, Ramsay E; et al. (2014). "Mutations in the DNA methyltransferase gene DNMT3A cause an overgrowth syndrome with intellectual disability". Nat Genet. 46 (4): 385–8. doi:10.1038/ng.2917. PMC 3981653. PMID 24614070.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ a b Tatton-Brown K, Zachariou A, Loveday C, Renwick A, Mahamdallie S; et al. (2018). "The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with de novo constitutive DNMT3A variants". Wellcome Open Res. 3: 46. doi:10.12688/wellcomeopenres.14430.1. PMC 5964628. PMID 29900417.
{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Jiménez de la Peña M, Rincón-Pérez I, López-Martín S, Albert J, Martín Fernández-Mayoralas D, Fernández-Perrone AL; et al. (2023). "Tatton-Brown-Rahman syndrome: Novel pathogenic variants and new neuroimaging findings". Am J Med Genet A. doi:10.1002/ajmg.a.63434. PMID 37795572.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Hamagami N, Wu DY, Clemens AW, Nettles SA, Li A, Gabel HW (2023). "NSD1 deposits histone H3 lysine 36 dimethylation to pattern non-CG DNA methylation in neurons". Mol Cell. 83 (9): 1412-1428.e7. doi:10.1016/j.molcel.2023.04.001. PMC 10230755. PMID 37098340.
{{cite journal}}: CS1 maint: multiple names: authors list (link)