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Intellectual disability, X-linked 104(XLID104)

MedGen UID:
934784
Concept ID:
C4310817
Disease or Syndrome
Synonyms: INTELLECTUAL DEVELOPMENTAL DISORDER, X-LINKED 104; XLID104
 
Gene (location): FRMPD4 (Xp22.2)
 
Monarch Initiative: MONDO:0010509
OMIM®: 300983

Definition

Any non-syndromic X-linked intellectual disability in which the cause of the disease is a mutation in the FRMPD4 gene. [from MONDO]

Clinical features

From HPO
Abnormal pinna morphology
MedGen UID:
167800
Concept ID:
C0857379
Congenital Abnormality
An abnormality of the pinna, which is also referred to as the auricle or external ear.
Aggressive behavior
MedGen UID:
1375
Concept ID:
C0001807
Individual Behavior
Behavior or an act aimed at harming a person, animal, or physical property (e.g., acts of physical violence; shouting, swearing, and using harsh language; slashing someone's tires).
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterised by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Delayed ability to walk
MedGen UID:
66034
Concept ID:
C0241726
Finding
A failure to achieve the ability to walk at an appropriate developmental stage. Most children learn to walk in a series of stages, and learn to walk short distances independently between 12 and 15 months.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Hyperactivity
MedGen UID:
98406
Concept ID:
C0424295
Finding
Hyperactivity is a condition characterized by constant and unusually high levels of activity, even in situations where it is deemed inappropriate.
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
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.
Reduced eye contact
MedGen UID:
303190
Concept ID:
C1445953
Finding
A reduced frequency or duration of eye contact.
Delayed gross motor development
MedGen UID:
332508
Concept ID:
C1837658
Finding
A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
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.
Delayed CNS myelination
MedGen UID:
867393
Concept ID:
C4021758
Anatomical Abnormality
Delayed myelination in the central nervous system.
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
Retrognathia
MedGen UID:
19766
Concept ID:
C0035353
Congenital Abnormality
An abnormality in which the mandible is mislocalised posteriorly.
Trigonocephaly
MedGen UID:
82713
Concept ID:
C0265535
Congenital Abnormality
Wedge-shaped, or triangular head, with the apex of the triangle at the midline of the forehead and the base of the triangle at the occiput.
High forehead
MedGen UID:
65991
Concept ID:
C0239676
Finding
An abnormally increased height of the forehead.
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).
Bifid nasal tip
MedGen UID:
140870
Concept ID:
C0426428
Finding
A splitting of the nasal tip. Visually assessable vertical indentation, cleft, or depression of the nasal tip.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Frontal upsweep of hair
MedGen UID:
452910
Concept ID:
C1185616
Finding
Upward and/or sideward growth of anterior hair.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.

Professional guidelines

PubMed

Goldstein DS, Holmes CS, Kaler SG
Neurochem Res 2009 Aug;34(8):1464-8. Epub 2009 Feb 21 doi: 10.1007/s11064-009-9933-8. PMID: 19234788Free PMC Article

Recent clinical studies

Etiology

Rattay TW, Rautenberg M, Söhn AS, Hengel H, Traschütz A, Röben B, Hayer SN, Schüle R, Wiethoff S, Zeltner L, Haack TB, Cegan A, Schöls L, Schleicher E, Peter A
Sci Rep 2020 Sep 15;10(1):15093. doi: 10.1038/s41598-020-71248-8. PMID: 32934269Free PMC Article
Huffnagel IC, Laheji FK, Aziz-Bose R, Tritos NA, Marino R, Linthorst GE, Kemp S, Engelen M, Eichler F
J Clin Endocrinol Metab 2019 Jan 1;104(1):118-126. doi: 10.1210/jc.2018-01307. PMID: 30252065
Pinto D, Pagnamenta AT, Klei L, Anney R, Merico D, Regan R, Conroy J, Magalhaes TR, Correia C, Abrahams BS, Almeida J, Bacchelli E, Bader GD, Bailey AJ, Baird G, Battaglia A, Berney T, Bolshakova N, Bölte S, Bolton PF, Bourgeron T, Brennan S, Brian J, Bryson SE, Carson AR, Casallo G, Casey J, Chung BH, Cochrane L, Corsello C, Crawford EL, Crossett A, Cytrynbaum C, Dawson G, de Jonge M, Delorme R, Drmic I, Duketis E, Duque F, Estes A, Farrar P, Fernandez BA, Folstein SE, Fombonne E, Freitag CM, Gilbert J, Gillberg C, Glessner JT, Goldberg J, Green A, Green J, Guter SJ, Hakonarson H, Heron EA, Hill M, Holt R, Howe JL, Hughes G, Hus V, Igliozzi R, Kim C, Klauck SM, Kolevzon A, Korvatska O, Kustanovich V, Lajonchere CM, Lamb JA, Laskawiec M, Leboyer M, Le Couteur A, Leventhal BL, Lionel AC, Liu XQ, Lord C, Lotspeich L, Lund SC, Maestrini E, Mahoney W, Mantoulan C, Marshall CR, McConachie H, McDougle CJ, McGrath J, McMahon WM, Merikangas A, Migita O, Minshew NJ, Mirza GK, Munson J, Nelson SF, Noakes C, Noor A, Nygren G, Oliveira G, Papanikolaou K, Parr JR, Parrini B, Paton T, Pickles A, Pilorge M, Piven J, Ponting CP, Posey DJ, Poustka A, Poustka F, Prasad A, Ragoussis J, Renshaw K, Rickaby J, Roberts W, Roeder K, Roge B, Rutter ML, Bierut LJ, Rice JP, Salt J, Sansom K, Sato D, Segurado R, Sequeira AF, Senman L, Shah N, Sheffield VC, Soorya L, Sousa I, Stein O, Sykes N, Stoppioni V, Strawbridge C, Tancredi R, Tansey K, Thiruvahindrapduram B, Thompson AP, Thomson S, Tryfon A, Tsiantis J, Van Engeland H, Vincent JB, Volkmar F, Wallace S, Wang K, Wang Z, Wassink TH, Webber C, Weksberg R, Wing K, Wittemeyer K, Wood S, Wu J, Yaspan BL, Zurawiecki D, Zwaigenbaum L, Buxbaum JD, Cantor RM, Cook EH, Coon H, Cuccaro ML, Devlin B, Ennis S, Gallagher L, Geschwind DH, Gill M, Haines JL, Hallmayer J, Miller J, Monaco AP, Nurnberger JI Jr, Paterson AD, Pericak-Vance MA, Schellenberg GD, Szatmari P, Vicente AM, Vieland VJ, Wijsman EM, Scherer SW, Sutcliffe JS, Betancur C
Nature 2010 Jul 15;466(7304):368-72. Epub 2010 Jun 9 doi: 10.1038/nature09146. PMID: 20531469Free PMC Article
Peters C, Charnas LR, Tan Y, Ziegler RS, Shapiro EG, DeFor T, Grewal SS, Orchard PJ, Abel SL, Goldman AI, Ramsay NK, Dusenbery KE, Loes DJ, Lockman LA, Kato S, Aubourg PR, Moser HW, Krivit W
Blood 2004 Aug 1;104(3):881-8. Epub 2004 Apr 8 doi: 10.1182/blood-2003-10-3402. PMID: 15073029
Castellví-Bel S, Milà M
Mol Genet Metab 2001 Feb;72(2):104-8. doi: 10.1006/mgme.2000.3128. PMID: 11161835

Diagnosis

Nagarajan B, Gowda VK, Yoganathan S, Sharawat IK, Srivastava K, Vora N, Badheka R, Danda S, Kalane U, Kaur A, Madaan P, Mehta S, Negi S, Panda PK, Rajadhyaksha S, Saini AG, Saini L, Shah S, Srinivasan VM, Suthar R, Thomas M, Vyas S, Sankhyan N, Sahu JK
Epilepsia Open 2023 Dec;8(4):1383-1404. Epub 2023 Aug 25 doi: 10.1002/epi4.12811. PMID: 37583270Free PMC Article
Rattay TW, Rautenberg M, Söhn AS, Hengel H, Traschütz A, Röben B, Hayer SN, Schüle R, Wiethoff S, Zeltner L, Haack TB, Cegan A, Schöls L, Schleicher E, Peter A
Sci Rep 2020 Sep 15;10(1):15093. doi: 10.1038/s41598-020-71248-8. PMID: 32934269Free PMC Article
Huffnagel IC, Laheji FK, Aziz-Bose R, Tritos NA, Marino R, Linthorst GE, Kemp S, Engelen M, Eichler F
J Clin Endocrinol Metab 2019 Jan 1;104(1):118-126. doi: 10.1210/jc.2018-01307. PMID: 30252065
Schenkel LC, Kernohan KD, McBride A, Reina D, Hodge A, Ainsworth PJ, Rodenhiser DI, Pare G, Bérubé NG, Skinner C, Boycott KM, Schwartz C, Sadikovic B
Epigenetics Chromatin 2017;10:10. Epub 2017 Mar 10 doi: 10.1186/s13072-017-0118-4. PMID: 28293299Free PMC Article
Rogers RC, Stevenson RE, Simensen RJ, Holden KR, Schwartz CE
Dev Med Child Neurol 2008 Feb;50(2):104-11. Epub 2008 Jan 7 doi: 10.1111/j.1469-8749.2007.02022.x. PMID: 18190539

Therapy

Santosh PJ, Bell L, Lievesley K, Singh J, Fiori F
BMC Pediatr 2016 Nov 29;16(1):194. doi: 10.1186/s12887-016-0734-3. PMID: 27899087Free PMC Article
Ahmed MA, Kartha RV, Brundage RC, Cloyd J, Basu C, Carlin BP, Jones RO, Moser AB, Fatemi A, Raymond GV
Br J Clin Pharmacol 2016 Jun;81(6):1058-66. Epub 2016 Apr 3 doi: 10.1111/bcp.12897. PMID: 26836218Free PMC Article
Wémeau JL, Pigeyre M, Proust-Lemoine E, d'Herbomez M, Gottrand F, Jansen J, Visser TJ, Ladsous M
J Clin Endocrinol Metab 2008 Jun;93(6):2084-8. Epub 2008 Mar 11 doi: 10.1210/jc.2007-2719. PMID: 18334584
Peters C, Charnas LR, Tan Y, Ziegler RS, Shapiro EG, DeFor T, Grewal SS, Orchard PJ, Abel SL, Goldman AI, Ramsay NK, Dusenbery KE, Loes DJ, Lockman LA, Kato S, Aubourg PR, Moser HW, Krivit W
Blood 2004 Aug 1;104(3):881-8. Epub 2004 Apr 8 doi: 10.1182/blood-2003-10-3402. PMID: 15073029
Naito E, Ito M, Yokota I, Saijo T, Matsuda J, Osaka H, Kimura S, Kuroda Y
J Inherit Metab Dis 1997 Aug;20(4):539-48. doi: 10.1023/a:1005305614374. PMID: 9266390

Prognosis

Rattay TW, Rautenberg M, Söhn AS, Hengel H, Traschütz A, Röben B, Hayer SN, Schüle R, Wiethoff S, Zeltner L, Haack TB, Cegan A, Schöls L, Schleicher E, Peter A
Sci Rep 2020 Sep 15;10(1):15093. doi: 10.1038/s41598-020-71248-8. PMID: 32934269Free PMC Article
Greene D; NIHR BioResource, Richardson S, Turro E
Am J Hum Genet 2017 Jul 6;101(1):104-114. Epub 2017 Jun 29 doi: 10.1016/j.ajhg.2017.05.015. PMID: 28669401Free PMC Article
Wang Y, Busin R, Reeves C, Bezman L, Raymond G, Toomer CJ, Watkins PA, Snowden A, Moser A, Naidu S, Bibat G, Hewson S, Tam K, Clarke JT, Charnas L, Stetten G, Karczeski B, Cutting G, Steinberg S
Mol Genet Metab 2011 Sep-Oct;104(1-2):160-6. Epub 2011 Jun 22 doi: 10.1016/j.ymgme.2011.05.016. PMID: 21700483
Peters C, Charnas LR, Tan Y, Ziegler RS, Shapiro EG, DeFor T, Grewal SS, Orchard PJ, Abel SL, Goldman AI, Ramsay NK, Dusenbery KE, Loes DJ, Lockman LA, Kato S, Aubourg PR, Moser HW, Krivit W
Blood 2004 Aug 1;104(3):881-8. Epub 2004 Apr 8 doi: 10.1182/blood-2003-10-3402. PMID: 15073029
Walpole SM, Ronce N, Grayson C, Dessay B, Yates JR, Trump D, Toutain A
Hum Genet 1999 May;104(5):410-1. doi: 10.1007/s004390050976. PMID: 10394933

Clinical prediction guides

Nagarajan B, Gowda VK, Yoganathan S, Sharawat IK, Srivastava K, Vora N, Badheka R, Danda S, Kalane U, Kaur A, Madaan P, Mehta S, Negi S, Panda PK, Rajadhyaksha S, Saini AG, Saini L, Shah S, Srinivasan VM, Suthar R, Thomas M, Vyas S, Sankhyan N, Sahu JK
Epilepsia Open 2023 Dec;8(4):1383-1404. Epub 2023 Aug 25 doi: 10.1002/epi4.12811. PMID: 37583270Free PMC Article
Della Vecchia S, Lopergolo D, Trovato R, Pasquariello R, Ferrari AR, Bartolini E
Seizure 2023 Jan;104:32-37. Epub 2022 Nov 29 doi: 10.1016/j.seizure.2022.11.014. PMID: 36476360
Rattay TW, Rautenberg M, Söhn AS, Hengel H, Traschütz A, Röben B, Hayer SN, Schüle R, Wiethoff S, Zeltner L, Haack TB, Cegan A, Schöls L, Schleicher E, Peter A
Sci Rep 2020 Sep 15;10(1):15093. doi: 10.1038/s41598-020-71248-8. PMID: 32934269Free PMC Article
Greene D; NIHR BioResource, Richardson S, Turro E
Am J Hum Genet 2017 Jul 6;101(1):104-114. Epub 2017 Jun 29 doi: 10.1016/j.ajhg.2017.05.015. PMID: 28669401Free PMC Article
Peters C, Charnas LR, Tan Y, Ziegler RS, Shapiro EG, DeFor T, Grewal SS, Orchard PJ, Abel SL, Goldman AI, Ramsay NK, Dusenbery KE, Loes DJ, Lockman LA, Kato S, Aubourg PR, Moser HW, Krivit W
Blood 2004 Aug 1;104(3):881-8. Epub 2004 Apr 8 doi: 10.1182/blood-2003-10-3402. PMID: 15073029

Recent systematic reviews

Della Vecchia S, Lopergolo D, Trovato R, Pasquariello R, Ferrari AR, Bartolini E
Seizure 2023 Jan;104:32-37. Epub 2022 Nov 29 doi: 10.1016/j.seizure.2022.11.014. PMID: 36476360

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