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Paraplegia-intellectual disability-hyperkeratosis syndrome

MedGen UID:
411554
Concept ID:
C2745996
Disease or Syndrome
Synonyms: Fitzsimmons-McLachlan-Gilbert syndrome; Mental retardation with spastic paraplegia and palmoplantar hyperkeratosis
SNOMED CT: Fitzsimmons McLachlan Gilbert syndrome (722209002); Spastic paraplegia, intellectual disability, palmoplantar hyperkeratosis syndrome (722209002)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Monarch Initiative: MONDO:0010662
OMIM®: 309560
Orphanet: ORPHA2824

Definition

This syndrome has characteristics of intellectual deficit, spasticity in the lower limbs (spastic paraplegia), pes cavus deformity of both feet, an abnormal gait, and palmar and plantar hyperkeratosis. It has been reported in four brothers. The mother of the affected boys had normal intelligence, plantar hyperkeratosis and a strong facial resemblance to her retarded sons. Her three daughters were normal. This syndrome most likely an X-linked recessive condition. [from SNOMEDCT_US]

Clinical features

From HPO
Palmoplantar keratosis
MedGen UID:
44017
Concept ID:
C0022596
Disease or Syndrome
Abnormal thickening of the skin localized to the palm of the hand and the sole of the foot.
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight).
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.
Spastic paraplegia
MedGen UID:
20882
Concept ID:
C0037772
Disease or Syndrome
Spasticity and weakness of the leg and hip muscles.
Tremor
MedGen UID:
21635
Concept ID:
C0040822
Sign or Symptom
An unintentional, oscillating to-and-fro muscle movement about a joint axis.
Brisk reflexes
MedGen UID:
382164
Concept ID:
C2673700
Finding
Tendon reflexes that are noticeably more active than usual (conventionally denoted 3+ on clinical examination). Brisk reflexes may or may not indicate a neurological lesion. They are distinguished from hyperreflexia by the fact that hyerreflexia is characterized by hyperactive repeating (clonic) reflexes, which are considered to be always abnormal.
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.
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).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • Paraplegia-intellectual disability-hyperkeratosis syndrome
Follow this link to review classifications for Paraplegia-intellectual disability-hyperkeratosis syndrome in Orphanet.

Professional guidelines

PubMed

Styne DM, Arslanian SA, Connor EL, Farooqi IS, Murad MH, Silverstein JH, Yanovski JA
J Clin Endocrinol Metab 2017 Mar 1;102(3):709-757. doi: 10.1210/jc.2016-2573. PMID: 28359099Free PMC Article
Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, Decaux G, Fenske W, Hoorn EJ, Ichai C, Joannidis M, Soupart A, Zietse R, Haller M, van der Veer S, Van Biesen W, Nagler E; Hyponatraemia Guideline Development Group
Eur J Endocrinol 2014 Mar;170(3):G1-47. Epub 2014 Feb 25 doi: 10.1530/EJE-13-1020. PMID: 24569125
Verbalis JG, Goldsmith SR, Greenberg A, Korzelius C, Schrier RW, Sterns RH, Thompson CJ
Am J Med 2013 Oct;126(10 Suppl 1):S1-42. doi: 10.1016/j.amjmed.2013.07.006. PMID: 24074529

Recent clinical studies

Etiology

Keith KA, Reed LK, Nguyen A, Qaiser R
Neurosurg Clin N Am 2022 Jan;33(1):135-148. doi: 10.1016/j.nec.2021.09.010. PMID: 34801137
Bautista G
Neoreviews 2021 Apr;22(4):e250-e257. doi: 10.1542/neo.22-4-e250. PMID: 33795400
Valdebran M, Wine Lee L
Curr Opin Pediatr 2020 Aug;32(4):498-505. doi: 10.1097/MOP.0000000000000925. PMID: 32692048
Poh TY, Mac Aogáin M, Chan AK, Yii AC, Yong VF, Tiew PY, Koh MS, Chotirmall SH
Expert Rev Respir Med 2017 Apr;11(4):285-298. Epub 2017 Mar 24 doi: 10.1080/17476348.2017.1305895. PMID: 28282995
Cereda A, Carey JC
Orphanet J Rare Dis 2012 Oct 23;7:81. doi: 10.1186/1750-1172-7-81. PMID: 23088440Free PMC Article

Diagnosis

Koster MJ, Samec MJ, Warrington KJ
J Clin Rheumatol 2023 Sep 1;29(6):298-306. Epub 2022 Oct 17 doi: 10.1097/RHU.0000000000001905. PMID: 36251488
Keith KA, Reed LK, Nguyen A, Qaiser R
Neurosurg Clin N Am 2022 Jan;33(1):135-148. doi: 10.1016/j.nec.2021.09.010. PMID: 34801137
De Wel B, Claeys KG
Curr Opin Neurol 2021 Oct 1;34(5):714-720. doi: 10.1097/WCO.0000000000000963. PMID: 34914668
Geenen KR, Patel S, Thiele EA
Dev Med Child Neurol 2021 Mar;63(3):259-262. Epub 2020 Oct 31 doi: 10.1111/dmcn.14723. PMID: 33135153
Diñeiro M, Capín R, Cifuentes GÁ, Fernández-Vega B, Villota E, Otero A, Santiago A, Pruneda PC, Castillo D, Viejo-Díaz M, Hernando I, Durán NS, Álvarez R, Lago CG, Ordóñez GR, Fernández-Vega Á, Cabanillas R, Cadiñanos J
Acta Ophthalmol 2020 Dec;98(8):e1034-e1048. Epub 2020 Jun 1 doi: 10.1111/aos.14479. PMID: 32483926Free PMC Article

Therapy

Dou Z, Xia Y, Zhang J, Li Y, Zhang Y, Zhao L, Huang Z, Sun H, Wu L, Han D, Liu Y
Front Endocrinol (Lausanne) 2021;12:728032. Epub 2021 Dec 23 doi: 10.3389/fendo.2021.728032. PMID: 35002950Free PMC Article
Saha S, Roy P, Corbitt C, Kakar SS
Cells 2021 Jun 28;10(7) doi: 10.3390/cells10071613. PMID: 34203240Free PMC Article
Geenen KR, Patel S, Thiele EA
Dev Med Child Neurol 2021 Mar;63(3):259-262. Epub 2020 Oct 31 doi: 10.1111/dmcn.14723. PMID: 33135153
Kagan R, Kellogg-Spadt S, Parish SJ
Drugs Aging 2019 Oct;36(10):897-908. doi: 10.1007/s40266-019-00700-w. PMID: 31452067Free PMC Article
Sosa-Reina MD, Nunez-Nagy S, Gallego-Izquierdo T, Pecos-Martín D, Monserrat J, Álvarez-Mon M
Biomed Res Int 2017;2017:2356346. Epub 2017 Sep 20 doi: 10.1155/2017/2356346. PMID: 29291206Free PMC Article

Prognosis

Fardeau C, Alafaleq M, Dhaenens CM, Dollfus H, Koné-Paut I, Grunewald O, Morel JB, Titah C, Saadoun D, Lazeran PO, Meunier I
Clin Genet 2023 Apr;103(4):453-458. Epub 2022 Dec 30 doi: 10.1111/cge.14286. PMID: 36543582
Košutova P, Mikolka P
Physiol Res 2021 Dec 30;70(Suppl4):S567-S583. doi: 10.33549/physiolres.934767. PMID: 35199544Free PMC Article
Cristescu Teodor R, Mihaltan FD
Rom J Ophthalmol 2019 Jan-Mar;63(1):2-9. PMID: 31198891Free PMC Article
Park CY, Lee JK, Chuck RS
BMC Ophthalmol 2018 Oct 25;18(1):276. doi: 10.1186/s12886-018-0939-3. PMID: 30359246Free PMC Article
Damgaard Sandahl T
Dan Med J 2014 Oct;61(10):B4755. PMID: 25283626

Clinical prediction guides

Boßelmann CM
Seizure 2021 Nov;92:230-233. Epub 2021 Sep 27 doi: 10.1016/j.seizure.2021.09.019. PMID: 34607271
Nazerian P, Mueller C, Soeiro AM, Leidel BA, Salvadeo SAT, Giachino F, Vanni S, Grimm K, Oliveira MT Jr, Pivetta E, Lupia E, Grifoni S, Morello F; ADvISED Investigators
Circulation 2018 Jan 16;137(3):250-258. Epub 2017 Oct 13 doi: 10.1161/CIRCULATIONAHA.117.029457. PMID: 29030346
Clemens RK, Pfammatter T, Meier TO, Alomari AI, Amann-Vesti BR
Vasa 2015 Mar;44(2):92-105. doi: 10.1024/0301-1526/a000414. PMID: 25698387
Gallentine WB, Mikati MA
J Clin Neurophysiol 2012 Oct;29(5):408-19. doi: 10.1097/WNP.0b013e31826bd92a. PMID: 23027098
Wijdicks EF, Bamlet WR, Maramattom BV, Manno EM, McClelland RL
Ann Neurol 2005 Oct;58(4):585-93. doi: 10.1002/ana.20611. PMID: 16178024

Recent systematic reviews

Freitas DA, Souza-Santos R, Carvalho LMA, Barros WB, Neves LM, Brasil P, Wakimoto MD
PLoS One 2020;15(12):e0242367. Epub 2020 Dec 15 doi: 10.1371/journal.pone.0242367. PMID: 33320867Free PMC Article
Sosa-Reina MD, Nunez-Nagy S, Gallego-Izquierdo T, Pecos-Martín D, Monserrat J, Álvarez-Mon M
Biomed Res Int 2017;2017:2356346. Epub 2017 Sep 20 doi: 10.1155/2017/2356346. PMID: 29291206Free PMC Article
Sorensen CJ, DeSanto K, Borgelt L, Phillips KT, Monte AA
J Med Toxicol 2017 Mar;13(1):71-87. Epub 2016 Dec 20 doi: 10.1007/s13181-016-0595-z. PMID: 28000146Free PMC Article
Canavan TN, Mathes EF, Frieden I, Shinkai K
J Am Acad Dermatol 2015 Feb;72(2):239-45. doi: 10.1016/j.jaad.2014.06.026. PMID: 25592340
Terelak-Borys B, Skonieczna K, Grabska-Liberek I
Med Sci Monit 2012 Aug;18(8):RA138-144. doi: 10.12659/msm.883260. PMID: 22847215Free PMC Article

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