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Syndromic X-linked intellectual disability 14(MRXS14)

MedGen UID:
372646
Concept ID:
C1970822
Disease or Syndrome
Synonyms: INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED, SYNDROMIC 14; MRXS14
 
Gene (location): UPF3B (Xq24)
 
Monarch Initiative: MONDO:0010398
OMIM®: 300676

Definition

Any X-linked syndromic intellectual disability in which the cause of the disease is a mutation in the UPF3B gene. [from MONDO]

Clinical features

From HPO
Long foot
MedGen UID:
154365
Concept ID:
C0576225
Finding
Increased back to front length of the foot.
Long palm
MedGen UID:
869005
Concept ID:
C4023422
Finding
For children from birth to 16 years of age the length of the palm is more than the 97th centile; or, the length of the palm appears relatively long compared to the finger length or the limb length.
Tall stature
MedGen UID:
69137
Concept ID:
C0241240
Finding
A height above that which is expected according to age and gender norms.
Slender build
MedGen UID:
376828
Concept ID:
C1850573
Finding
Asthenic habitus refers to a slender build with long limbs, an angular profile, and prominent muscles or bones.
Chronic constipation
MedGen UID:
98325
Concept ID:
C0401149
Sign or Symptom
Constipation for longer than three months with fewer than 3 bowel movements per week, straining, lumpy or hard stools, and a sensation of anorectal obstruction or incomplete defecation.
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Autistic behavior
MedGen UID:
163547
Concept ID:
C0856975
Mental or Behavioral Dysfunction
Persistent deficits in social interaction and communication and interaction as well as a markedly restricted repertoire of activity and interest as well as repetitive patterns of behavior.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Pectus carinatum
MedGen UID:
57643
Concept ID:
C0158731
Finding
A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum.
Hypoplasia of the maxilla
MedGen UID:
66804
Concept ID:
C0240310
Congenital Abnormality
Abnormally small dimension of the Maxilla. Usually creating a malocclusion or malalignment between the upper and lower teeth or resulting in a deficient amount of projection of the base of the nose and lower midface region.
Narrow chest
MedGen UID:
96528
Concept ID:
C0426790
Finding
Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder.
Pectus excavatum
MedGen UID:
781174
Concept ID:
C2051831
Finding
A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Hypernasal speech
MedGen UID:
99115
Concept ID:
C0454555
Finding
A type of speech characterized by the presence of an abnormally increased nasal airflow during speech associated with structural abnormality of the nasal passages.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Long face
MedGen UID:
324419
Concept ID:
C1836047
Finding
Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective).
Prominent forehead
MedGen UID:
373291
Concept ID:
C1837260
Finding
Forward prominence of the entire forehead, due to protrusion of the frontal bone.
Narrow face
MedGen UID:
373334
Concept ID:
C1837463
Finding
Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective).
Prominent nasal bridge
MedGen UID:
343051
Concept ID:
C1854113
Finding
Anterior positioning of the nasal root in comparison to the usual positioning for age.

Professional guidelines

PubMed

Vilvarajan S, McDonald M, Douglas L, Newham J, Kirkland R, Tzannes G, Tay D, Christodoulou J, Thompson S, Ellaway C
Genes (Basel) 2023 Aug 11;14(8) doi: 10.3390/genes14081607. PMID: 37628658Free PMC Article
Bozarth XL, Lopez J, Fang H, Lee-Eng J, Duan Z, Deng X
Genes (Basel) 2023 Mar 31;14(4) doi: 10.3390/genes14040852. PMID: 37107610Free PMC Article
Buchanan CB, Stallworth JL, Joy AE, Dixon RE, Scott AE, Beisang AA, Benke TA, Glaze DG, Haas RH, Heydemann PT, Jones MD, Lane JB, Lieberman DN, Marsh ED, Neul JL, Peters SU, Ryther RC, Skinner SA, Standridge SM, Kaufmann WE, Percy AK
J Neurodev Disord 2022 May 14;14(1):31. doi: 10.1186/s11689-022-09432-2. PMID: 35568815Free PMC Article

Recent clinical studies

Etiology

Shepherdson JL, Hutchison K, Don DW, McGillivray G, Choi TI, Allan CA, Amor DJ, Banka S, Basel DG, Buch LD, Carere DA, Carroll R, Clayton-Smith J, Crawford A, Dunø M, Faivre L, Gilfillan CP, Gold NB, Gripp KW, Hobson E, Holtz AM, Innes AM, Isidor B, Jackson A, Katsonis P, Amel Riazat Kesh L; Genomics England Research Consortium, Küry S, Lecoquierre F, Lockhart P, Maraval J, Matsumoto N, McCarrier J, McCarthy J, Miyake N, Moey LH, Németh AH, Østergaard E, Patel R, Pope K, Posey JE, Schnur RE, Shaw M, Stolerman E, Taylor JP, Wadman E, Wakeling E, White SM, Wong LC, Lupski JR, Lichtarge O, Corbett MA, Gecz J, Nicolet CM, Farnham PJ, Kim CH, Shinawi M
Am J Hum Genet 2024 Mar 7;111(3):487-508. Epub 2024 Feb 6 doi: 10.1016/j.ajhg.2024.01.007. PMID: 38325380Free PMC Article
Vilvarajan S, McDonald M, Douglas L, Newham J, Kirkland R, Tzannes G, Tay D, Christodoulou J, Thompson S, Ellaway C
Genes (Basel) 2023 Aug 11;14(8) doi: 10.3390/genes14081607. PMID: 37628658Free PMC Article
Storey E
Semin Neurol 2014 Jul;34(3):280-92. Epub 2014 Sep 5 doi: 10.1055/s-0034-1386766. PMID: 25192506
Lisik MZ, Sieron AL
Med Sci Monit 2008 Nov;14(11):RA221-9. PMID: 18971887
Raymond GV
Curr Opin Neurol 2001 Dec;14(6):783-7. doi: 10.1097/00019052-200112000-00017. PMID: 11723389

Diagnosis

Eichler F, Duncan CN, Musolino PL, Lund TC, Gupta AO, De Oliveira S, Thrasher AJ, Aubourg P, Kühl JS, Loes DJ, Amartino H, Smith N, Folloni Fernandes J, Sevin C, Sankar R, Hussain SA, Gissen P, Dalle JH, Platzbecker U, Downey GF, McNeil E, Demopoulos L, Dietz AC, Thakar HL, Orchard PJ, Williams DA
N Engl J Med 2024 Oct 10;391(14):1302-1312. doi: 10.1056/NEJMoa2400442. PMID: 39383459
Vilvarajan S, McDonald M, Douglas L, Newham J, Kirkland R, Tzannes G, Tay D, Christodoulou J, Thompson S, Ellaway C
Genes (Basel) 2023 Aug 11;14(8) doi: 10.3390/genes14081607. PMID: 37628658Free PMC Article
Küry S, Zhang J, Besnard T, Caro-Llopis A, Zeng X, Robert SM, Josiah SS, Kiziltug E, Denommé-Pichon AS, Cogné B, Kundishora AJ, Hao LT, Li H, Stevenson RE, Louie RJ, Deb W, Torti E, Vignard V, McWalter K, Raymond FL, Rajabi F, Ranza E, Grozeva D, Coury SA, Blanc X, Brischoux-Boucher E, Keren B, Õunap K, Reinson K, Ilves P, Wentzensen IM, Barr EE, Guihard SH, Charles P, Seaby EG, Monaghan KG, Rio M, van Bever Y, van Slegtenhorst M, Chung WK, Wilson A, Quinquis D, Bréhéret F, Retterer K, Lindenbaum P, Scalais E, Rhodes L, Stouffs K, Pereira EM, Berger SM, Milla SS, Jaykumar AB, Cobb MH, Panchagnula S, Duy PQ, Vincent M, Mercier S, Gilbert-Dussardier B, Le Guillou X, Audebert-Bellanger S, Odent S, Schmitt S, Boisseau P, Bonneau D, Toutain A, Colin E, Pasquier L, Redon R, Bouman A, Rosenfeld JA, Friez MJ, Pérez-Peña H, Akhtar Rizvi SR, Haider S, Antonarakis SE, Schwartz CE, Martínez F, Bézieau S, Kahle KT, Isidor B
Genet Med 2022 Sep;24(9):1941-1951. Epub 2022 Jun 9 doi: 10.1016/j.gim.2022.05.009. PMID: 35678782
Storey E
Semin Neurol 2014 Jul;34(3):280-92. Epub 2014 Sep 5 doi: 10.1055/s-0034-1386766. PMID: 25192506
Raymond GV
Curr Opin Neurol 2001 Dec;14(6):783-7. doi: 10.1097/00019052-200112000-00017. PMID: 11723389

Therapy

Eichler F, Duncan CN, Musolino PL, Lund TC, Gupta AO, De Oliveira S, Thrasher AJ, Aubourg P, Kühl JS, Loes DJ, Amartino H, Smith N, Folloni Fernandes J, Sevin C, Sankar R, Hussain SA, Gissen P, Dalle JH, Platzbecker U, Downey GF, McNeil E, Demopoulos L, Dietz AC, Thakar HL, Orchard PJ, Williams DA
N Engl J Med 2024 Oct 10;391(14):1302-1312. doi: 10.1056/NEJMoa2400442. PMID: 39383459
Curie A, Lion-François L, Valayannopoulos V, Perreton N, Gavanon M, Touil N, Brun-Laurisse A, Gheurbi F, Buchy M, Halep H, Cheillan D, Mercier C, Brassier A, Desnous B, Kassai B, De Lonlay P, Des Portes V
Neurology 2024 Apr 23;102(8):e209243. Epub 2024 Mar 26 doi: 10.1212/WNL.0000000000209243. PMID: 38531017
Zung A, Sonntag N, Schweizer U, Banne E, Braun D
J Clin Endocrinol Metab 2024 Sep 16;109(10):2589-2601. doi: 10.1210/clinem/dgae146. PMID: 38469646
Buchanan CB, Stallworth JL, Joy AE, Dixon RE, Scott AE, Beisang AA, Benke TA, Glaze DG, Haas RH, Heydemann PT, Jones MD, Lane JB, Lieberman DN, Marsh ED, Neul JL, Peters SU, Ryther RC, Skinner SA, Standridge SM, Kaufmann WE, Percy AK
J Neurodev Disord 2022 May 14;14(1):31. doi: 10.1186/s11689-022-09432-2. PMID: 35568815Free PMC Article
van Geest FS, Groeneweg S, van den Akker ELT, Bacos I, Barca D, van den Berg SAA, Bertini E, Brunner D, Brunetti-Pierri N, Cappa M, Cappuccio G, Chatterjee K, Chesover AD, Christian P, Coutant R, Craiu D, Crock P, Dewey C, Dica A, Dimitri P, Dubey R, Enderli A, Fairchild J, Gallichan J, Garibaldi LR, George B, Hackenberg A, Heinrich B, Huynh T, Kłosowska A, Lawson-Yuen A, Linder-Lucht M, Lyons G, Monti Lora F, Moran C, Müller KE, Paone L, Paul PG, Polak M, Porta F, Reinauer C, de Rijke YB, Seckold R, Menevşe TS, Simm P, Simon A, Spada M, Stoupa A, Szeifert L, Tonduti D, van Toor H, Turan S, Vanderniet J, de Waart M, van der Wal R, van der Walt A, van Wermeskerken AM, Wierzba J, Zibordi F, Zung A, Peeters RP, Visser WE
J Clin Endocrinol Metab 2022 Feb 17;107(3):e1136-e1147. doi: 10.1210/clinem/dgab750. PMID: 34679181Free PMC Article

Prognosis

Eichler F, Duncan CN, Musolino PL, Lund TC, Gupta AO, De Oliveira S, Thrasher AJ, Aubourg P, Kühl JS, Loes DJ, Amartino H, Smith N, Folloni Fernandes J, Sevin C, Sankar R, Hussain SA, Gissen P, Dalle JH, Platzbecker U, Downey GF, McNeil E, Demopoulos L, Dietz AC, Thakar HL, Orchard PJ, Williams DA
N Engl J Med 2024 Oct 10;391(14):1302-1312. doi: 10.1056/NEJMoa2400442. PMID: 39383459
Vilvarajan S, McDonald M, Douglas L, Newham J, Kirkland R, Tzannes G, Tay D, Christodoulou J, Thompson S, Ellaway C
Genes (Basel) 2023 Aug 11;14(8) doi: 10.3390/genes14081607. PMID: 37628658Free PMC Article
Steele JL, Morrow MM, Sarnat HB, Alkhunaizi E, Brandt T, Chitayat DA, DeFilippo CP, Douglas GV, Dubbs HA, Elloumi HZ, Glassford MR, Hannibal MC, Héron B, Kim LE, Marco EJ, Mignot C, Monaghan KG, Myers KA, Parikh S, Quinonez SC, Rajabi F, Shankar SP, Shinawi MS, van de Kamp JJP, Veerapandiyan A, Waldman AT, Graf WD
Pediatr Neurol 2022 Jan;126:65-73. Epub 2021 Oct 18 doi: 10.1016/j.pediatrneurol.2021.10.008. PMID: 34740135
van Geest FS, Groeneweg S, van den Akker ELT, Bacos I, Barca D, van den Berg SAA, Bertini E, Brunner D, Brunetti-Pierri N, Cappa M, Cappuccio G, Chatterjee K, Chesover AD, Christian P, Coutant R, Craiu D, Crock P, Dewey C, Dica A, Dimitri P, Dubey R, Enderli A, Fairchild J, Gallichan J, Garibaldi LR, George B, Hackenberg A, Heinrich B, Huynh T, Kłosowska A, Lawson-Yuen A, Linder-Lucht M, Lyons G, Monti Lora F, Moran C, Müller KE, Paone L, Paul PG, Polak M, Porta F, Reinauer C, de Rijke YB, Seckold R, Menevşe TS, Simm P, Simon A, Spada M, Stoupa A, Szeifert L, Tonduti D, van Toor H, Turan S, Vanderniet J, de Waart M, van der Wal R, van der Walt A, van Wermeskerken AM, Wierzba J, Zibordi F, Zung A, Peeters RP, Visser WE
J Clin Endocrinol Metab 2022 Feb 17;107(3):e1136-e1147. doi: 10.1210/clinem/dgab750. PMID: 34679181Free PMC Article
Lisik MZ, Sieron AL
Med Sci Monit 2008 Nov;14(11):RA221-9. PMID: 18971887

Clinical prediction guides

Shepherdson JL, Hutchison K, Don DW, McGillivray G, Choi TI, Allan CA, Amor DJ, Banka S, Basel DG, Buch LD, Carere DA, Carroll R, Clayton-Smith J, Crawford A, Dunø M, Faivre L, Gilfillan CP, Gold NB, Gripp KW, Hobson E, Holtz AM, Innes AM, Isidor B, Jackson A, Katsonis P, Amel Riazat Kesh L; Genomics England Research Consortium, Küry S, Lecoquierre F, Lockhart P, Maraval J, Matsumoto N, McCarrier J, McCarthy J, Miyake N, Moey LH, Németh AH, Østergaard E, Patel R, Pope K, Posey JE, Schnur RE, Shaw M, Stolerman E, Taylor JP, Wadman E, Wakeling E, White SM, Wong LC, Lupski JR, Lichtarge O, Corbett MA, Gecz J, Nicolet CM, Farnham PJ, Kim CH, Shinawi M
Am J Hum Genet 2024 Mar 7;111(3):487-508. Epub 2024 Feb 6 doi: 10.1016/j.ajhg.2024.01.007. PMID: 38325380Free PMC Article
Rowland ME, Jiang Y, Shafiq S, Ghahramani A, Pena-Ortiz MA, Dumeaux V, Bérubé NG
Nat Commun 2023 Nov 4;14(1):7090. doi: 10.1038/s41467-023-42752-y. PMID: 37925436Free PMC Article
Jain V, Foo SH, Chooi S, Moss C, Goodwin R, Berland S, Clarke AJ, Davies SJ, Corrin S, Murch O, Doyle S, Graham GE, Greenhalgh L, Holder SE, Johnson D, Kumar A, Ladda RL, Sell S, Begtrup A, Lynch SA, McCann E, Østern R, Pottinger C, Splitt M, Fry AE
Eur J Hum Genet 2023 Dec;31(12):1421-1429. Epub 2023 Sep 14 doi: 10.1038/s41431-023-01447-0. PMID: 37704779Free PMC Article
Vilvarajan S, McDonald M, Douglas L, Newham J, Kirkland R, Tzannes G, Tay D, Christodoulou J, Thompson S, Ellaway C
Genes (Basel) 2023 Aug 11;14(8) doi: 10.3390/genes14081607. PMID: 37628658Free PMC Article
Moortgat S, Berland S, Aukrust I, Maystadt I, Baker L, Benoit V, Caro-Llopis A, Cooper NS, Debray FG, Faivre L, Gardeitchik T, Haukanes BI, Houge G, Kivuva E, Martinez F, Mehta SG, Nassogne MC, Powell-Hamilton N, Pfundt R, Rosello M, Prescott T, Vasudevan P, van Loon B, Verellen-Dumoulin C, Verloes A, Lippe CV, Wakeling E, Wilkie AOM, Wilson L, Yuen A, Study D, Low KJ, Newbury-Ecob RA
Eur J Hum Genet 2018 Jan;26(1):64-74. Epub 2017 Nov 27 doi: 10.1038/s41431-017-0038-6. PMID: 29180823Free PMC Article

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