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Peripheral neuropathy, autosomal recessive, with or without impaired intellectual development(PNRIID)

MedGen UID:
1648480
Concept ID:
C4748283
Disease or Syndrome
Synonyms: PERIPHERAL NEUROPATHY, AUTOSOMAL RECESSIVE, WITH OR WITHOUT IMPAIRED INTELLECTUAL DEVELOPMENT; PNRIID
 
Gene (location): MCM3AP (21q22.3)
 
Monarch Initiative: MONDO:0029131
OMIM®: 618124

Definition

Autosomal recessive peripheral neuropathy with or without impaired intellectual development is an early childhood-onset neurologic disorder characterized by slowly progressive distal motor impairment resulting in gait difficulties, often with loss of ambulation, and difficulties using the hands in most patients. Most affected individuals also have impaired intellectual development, although some have normal cognition. Electrophysiologic testing and sural nerve biopsy are most compatible with an axonal motor neuropathy; some patients may show signs of demyelination. Additional features may include eye movement abnormalities, claw hands, foot deformities, and scoliosis (summary by Ylikallio et al., 2017). [from OMIM]

Clinical features

From HPO
Premature ovarian insufficiency
MedGen UID:
9963
Concept ID:
C0025322
Disease or Syndrome
Amenorrhea due to loss of ovarian function before the age of 40. Primary ovarian inssuficiency (POI) is a state of female hypergonadotropic hypogonadism. It can manifest as primary amenorrhea with onset before menarche or secondary amenorrhea.
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).
Areflexia of lower limbs
MedGen UID:
347285
Concept ID:
C1856694
Finding
Inability to elicit tendon reflexes in the lower limbs.
Foot dorsiflexor weakness
MedGen UID:
356163
Concept ID:
C1866141
Finding
Weakness of the muscles responsible for dorsiflexion of the foot, that is, of the movement of the toes towards the shin. The foot dorsiflexors include the tibialis anterior, the extensor hallucis longus, the extensor digitorum longus, and the peroneus tertius muscles.
Split hand
MedGen UID:
397570
Concept ID:
C2699510
Congenital Abnormality
A condition in which middle parts of the hand (fingers and metacarpals) are missing giving a cleft appearance. The severity is very variable ranging from slightly hypoplastic middle fingers over absent middle fingers as far as oligo- or monodactyl hands.
Obesity
MedGen UID:
18127
Concept ID:
C0028754
Disease or Syndrome
Accumulation of substantial excess body fat.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
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).
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.
Unsteady gait
MedGen UID:
68544
Concept ID:
C0231686
Finding
A shaky or wobbly manner of walking.
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.
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.
Obstructive sleep apnea syndrome
MedGen UID:
101045
Concept ID:
C0520679
Disease or Syndrome
Obstructive sleep apnea is a common, chronic, complex disease associated with serious cardiovascular and neuropsychologic sequelae and with substantial social and economic costs (Palmer et al., 2003).
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Sensorimotor neuropathy
MedGen UID:
207266
Concept ID:
C1112256
Disease or Syndrome
Peripheral axonal neuropathy
MedGen UID:
266071
Concept ID:
C1263857
Disease or Syndrome
An abnormality characterized by disruption of the normal functioning of peripheral axons.
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
Impaired pain sensation
MedGen UID:
373348
Concept ID:
C1837522
Finding
Reduced ability to perceive painful stimuli.
Distal sensory impairment
MedGen UID:
335722
Concept ID:
C1847584
Finding
An abnormal reduction in sensation in the distal portions of the extremities.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
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.
Distal muscle weakness
MedGen UID:
140883
Concept ID:
C0427065
Finding
Reduced strength of the musculature of the distal extremities.
High, narrow palate
MedGen UID:
324787
Concept ID:
C1837404
Finding
The presence of a high and narrow palate.
Ophthalmoplegia
MedGen UID:
45205
Concept ID:
C0029089
Sign or Symptom
Paralysis of one or more extraocular muscles that are responsible for eye movements.
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.
Abnormality of eye movement
MedGen UID:
99227
Concept ID:
C0497202
Finding
An abnormality in voluntary or involuntary eye movements or their control.

Professional guidelines

PubMed

Keary CJ, McDougle CJ
Expert Rev Neurother 2023 Jul-Dec;23(9):835-844. Epub 2023 Aug 21 doi: 10.1080/14737175.2023.2245568. PMID: 37599585
Frank AJ, Dagogo-Jack I, Dobre IA, Tait S, Schumacher L, Fintelmann FJ, Fingerman LM, Keane FK, Montesi SB
Oncologist 2023 Jan 18;28(1):12-22. doi: 10.1093/oncolo/oyac226. PMID: 36426803Free PMC Article
O'Shea TM
Clin Obstet Gynecol 2008 Dec;51(4):816-28. doi: 10.1097/GRF.0b013e3181870ba7. PMID: 18981805Free PMC Article

Recent clinical studies

Etiology

Fink JK
Handb Clin Neurol 2023;196:59-88. doi: 10.1016/B978-0-323-98817-9.00022-3. PMID: 37620092
Zambon AA, Pini V, Bosco L, Falzone YM, Munot P, Muntoni F, Previtali SC
Brain 2023 Mar 1;146(3):806-822. doi: 10.1093/brain/awac452. PMID: 36445400Free PMC Article
Murala S, Nagarajan E, Bollu PC
Neurol Sci 2021 Mar;42(3):883-894. Epub 2021 Jan 13 doi: 10.1007/s10072-020-04981-7. PMID: 33439395
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Rogers EE, Hintz SR
Semin Perinatol 2016 Dec;40(8):497-509. Epub 2016 Nov 16 doi: 10.1053/j.semperi.2016.09.002. PMID: 27865437

Diagnosis

Fink JK
Handb Clin Neurol 2023;196:59-88. doi: 10.1016/B978-0-323-98817-9.00022-3. PMID: 37620092
Kramarz C, Rossor AM
J Neurol 2022 Sep;269(9):5187-5191. Epub 2022 May 21 doi: 10.1007/s00415-022-11164-1. PMID: 35596796Free PMC Article
Murala S, Nagarajan E, Bollu PC
Neurol Sci 2021 Mar;42(3):883-894. Epub 2021 Jan 13 doi: 10.1007/s10072-020-04981-7. PMID: 33439395
Ashrafi MR, Amanat M, Garshasbi M, Kameli R, Nilipour Y, Heidari M, Rezaei Z, Tavasoli AR
Expert Rev Neurother 2020 Jan;20(1):65-84. Epub 2019 Dec 12 doi: 10.1080/14737175.2020.1699060. PMID: 31829048
Morena J, Gupta A, Hoyle JC
Int J Mol Sci 2019 Jul 12;20(14) doi: 10.3390/ijms20143419. PMID: 31336816Free PMC Article

Therapy

Thapar A, Eyre O, Patel V, Brent D
Lancet 2022 Aug 20;400(10352):617-631. Epub 2022 Aug 5 doi: 10.1016/S0140-6736(22)01012-1. PMID: 35940184
Samanta D
Pediatr Neurol 2020 Apr;105:3-9. Epub 2019 Nov 30 doi: 10.1016/j.pediatrneurol.2019.10.009. PMID: 32057594
Morena J, Gupta A, Hoyle JC
Int J Mol Sci 2019 Jul 12;20(14) doi: 10.3390/ijms20143419. PMID: 31336816Free PMC Article
Bailey RL, West KP Jr, Black RE
Ann Nutr Metab 2015;66 Suppl 2:22-33. Epub 2015 Jun 2 doi: 10.1159/000371618. PMID: 26045325
Colver A, Fairhurst C, Pharoah PO
Lancet 2014 Apr 5;383(9924):1240-9. Epub 2013 Nov 20 doi: 10.1016/S0140-6736(13)61835-8. PMID: 24268104

Prognosis

Pipis M, Feely SME, Polke JM, Skorupinska M, Perez L, Shy RR, Laura M, Morrow JM, Moroni I, Pisciotta C, Taroni F, Vujovic D, Lloyd TE, Acsadi G, Yum SW, Lewis RA, Finkel RS, Herrmann DN, Day JW, Li J, Saporta M, Sadjadi R, Walk D, Burns J, Muntoni F, Ramchandren S, Horvath R, Johnson NE, Züchner S, Pareyson D, Scherer SS, Rossor AM, Shy ME, Reilly MM; Inherited Neuropathies Consortium - Rare Disease Clinical Research Network (INC-RDCRN)
Brain 2020 Dec 1;143(12):3589-3602. doi: 10.1093/brain/awaa323. PMID: 33415332Free PMC Article
Rogers EE, Hintz SR
Semin Perinatol 2016 Dec;40(8):497-509. Epub 2016 Nov 16 doi: 10.1053/j.semperi.2016.09.002. PMID: 27865437
O'Shea TM
Clin Obstet Gynecol 2008 Dec;51(4):816-28. doi: 10.1097/GRF.0b013e3181870ba7. PMID: 18981805Free PMC Article
Amaral DG, Schumann CM, Nordahl CW
Trends Neurosci 2008 Mar;31(3):137-45. Epub 2008 Feb 6 doi: 10.1016/j.tins.2007.12.005. PMID: 18258309
Hamel C
Orphanet J Rare Dis 2006 Oct 11;1:40. doi: 10.1186/1750-1172-1-40. PMID: 17032466Free PMC Article

Clinical prediction guides

Dominik N, Magri S, Currò R, Abati E, Facchini S, Corbetta M, Macpherson H, Di Bella D, Sarto E, Stevanovski I, Chintalaphani SR, Akcimen F, Manini A, Vegezzi E, Quartesan I, Montgomery KA, Pirota V, Crespan E, Perini C, Grupelli GP, Tomaselli PJ, Marques W; Genomics England Research Consortium, Shaw J, Polke J, Salsano E, Fenu S, Pareyson D, Pisciotta C, Tofaris GK, Nemeth AH, Ealing J, Radunovic A, Kearney S, Kumar KR, Vucic S, Kennerson M, Reilly MM, Houlden H, Deveson I, Tucci A, Taroni F, Cortese A
Brain 2023 Dec 1;146(12):5060-5069. doi: 10.1093/brain/awad240. PMID: 37450567Free PMC Article
Dupré M, Hermann R, Froment Tilikete C
Cerebellum 2021 Oct;20(5):687-700. Epub 2020 Oct 4 doi: 10.1007/s12311-020-01192-w. PMID: 33011895Free PMC Article
Pipis M, Feely SME, Polke JM, Skorupinska M, Perez L, Shy RR, Laura M, Morrow JM, Moroni I, Pisciotta C, Taroni F, Vujovic D, Lloyd TE, Acsadi G, Yum SW, Lewis RA, Finkel RS, Herrmann DN, Day JW, Li J, Saporta M, Sadjadi R, Walk D, Burns J, Muntoni F, Ramchandren S, Horvath R, Johnson NE, Züchner S, Pareyson D, Scherer SS, Rossor AM, Shy ME, Reilly MM; Inherited Neuropathies Consortium - Rare Disease Clinical Research Network (INC-RDCRN)
Brain 2020 Dec 1;143(12):3589-3602. doi: 10.1093/brain/awaa323. PMID: 33415332Free PMC Article
Fakhro KA
Adv Neurobiol 2020;24:83-96. doi: 10.1007/978-3-030-30402-7_3. PMID: 32006357
Amaral DG, Schumann CM, Nordahl CW
Trends Neurosci 2008 Mar;31(3):137-45. Epub 2008 Feb 6 doi: 10.1016/j.tins.2007.12.005. PMID: 18258309

Recent systematic reviews

Olusanya BO, Smythe T, Ogbo FA, Nair MKC, Scher M, Davis AC
Front Public Health 2023;11:1122009. Epub 2023 Feb 16 doi: 10.3389/fpubh.2023.1122009. PMID: 36891340Free PMC Article
Desaunay P, Eude LG, Dreyfus M, Alexandre C, Fedrizzi S, Alexandre J, Uguz F, Guénolé F
Paediatr Drugs 2023 May;25(3):247-265. Epub 2023 Feb 28 doi: 10.1007/s40272-023-00561-2. PMID: 36853497
Sacchi C, Marino C, Nosarti C, Vieno A, Visentin S, Simonelli A
JAMA Pediatr 2020 Aug 1;174(8):772-781. doi: 10.1001/jamapediatrics.2020.1097. PMID: 32453414Free PMC Article
Ruano L, Melo C, Silva MC, Coutinho P
Neuroepidemiology 2014;42(3):174-83. Epub 2014 Mar 5 doi: 10.1159/000358801. PMID: 24603320
Arbesman M, Bazyk S, Nochajski SM
Am J Occup Ther 2013 Nov-Dec;67(6):e120-30. doi: 10.5014/ajot.2013.008359. PMID: 24195907

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