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MEDNIK syndrome(MEDNIK)

MedGen UID:
322893
Concept ID:
C1836330
Disease or Syndrome
Synonyms: ERYTHROKERATODERMIA VARIABILIS, KAMOURASKA TYPE; MEDNIK
SNOMED CT: Intellectual disability, enteropathy, deafness, peripheral neuropathy, ichthyosis, keratoderma syndrome (722035007); MEDNIK syndrome (722035007); MEDNIK (mental retardation, enteropathy, deafness, peripheral neuropathy, ichtyosis, keratodermia) syndrome (722035007); Erythrokeratodermia variabilis 3 (722035007); Erythrokeratodermia variabilis Kamouraska type (722035007)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): AP1S1 (7q22.1)
 
Monarch Initiative: MONDO:0012251
OMIM®: 609313
Orphanet: ORPHA171851

Definition

MEDNIK syndrome is a severe multisystem disorder characterized by impaired intellectual development, enteropathy, deafness, peripheral neuropathy, ichthyosis, and keratoderma (summary by Montpetit et al., 2008). Patients with MEDNIK exhibit distinct dysmorphic features, including high forehead, upslanting palpebral fissures, depressed nasal bridge, and low-set ears, as well as growth retardation and moderate to severe intellectual disability, with brain atrophy on imaging. Other features include sensorineural deafness, enteropathy with congenital diarrhea, abnormalities of copper metabolism associated with liver disease, and ichthyosis, hyperkeratosis, and erythroderma. Peripheral neuropathy has also been observed in adult patients (Martinelli et al., 2013). MEDNIK syndrome shows phenotypic similarities to CEDNIK syndrome (609528). [from OMIM]

Clinical features

From HPO
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Cholestasis
MedGen UID:
925
Concept ID:
C0008370
Disease or Syndrome
Impairment of bile flow due to obstruction in bile ducts.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Cirrhosis of liver
MedGen UID:
7368
Concept ID:
C0023890
Disease or Syndrome
A chronic disorder of the liver in which liver tissue becomes scarred and is partially replaced by regenerative nodules and fibrotic tissue resulting in loss of liver function.
Volvulus
MedGen UID:
21892
Concept ID:
C0042961
Disease or Syndrome
Abnormal twisting of a portion of intestine around itself or around a stalk of mesentery tissue.
Hepatic fibrosis
MedGen UID:
116093
Concept ID:
C0239946
Disease or Syndrome
The presence of excessive fibrous connective tissue in the liver. Fibrosis is a reparative or reactive process.
Jejunal atresia
MedGen UID:
75603
Concept ID:
C0266175
Congenital Abnormality
Jejunal atresia is the most common cause of bowel obstruction in the newborn. In this condition, because of agenesis of the mesentery, the distal small bowel comes straight off the caecum and twists around the marginal artery, suggesting a maypole, a Christmas tree, or an apple peel at operation. Obliteration of the superior mesenteric artery may underlie this malformation.
Microcolon
MedGen UID:
82734
Concept ID:
C0266200
Congenital Abnormality
A colon of abnormally small caliber.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Peripheral neuropathy
MedGen UID:
18386
Concept ID:
C0031117
Disease or Syndrome
Peripheral neuropathy is a general term for any disorder of the peripheral nervous system. The main clinical features used to classify peripheral neuropathy are distribution, type (mainly demyelinating versus mainly axonal), duration, and course.
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.
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.
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.
Increased circulating very long-chain fatty acid concentration
MedGen UID:
1788690
Concept ID:
C5539740
Finding
Increased concentration of very long-chain fatty acids in the blood circulation. Very long-chain fatty acids are fatty acids (FAs) with a chain-length of 22 or more carbons.
High forehead
MedGen UID:
65991
Concept ID:
C0239676
Finding
An abnormally increased height of the forehead.
Upslanted palpebral fissure
MedGen UID:
98390
Concept ID:
C0423109
Finding
The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age.
Ichthyosis
MedGen UID:
7002
Concept ID:
C0020757
Disease or Syndrome
An abnormality of the skin characterized the presence of excessive amounts of dry surface scales on the skin resulting from an abnormality of keratinization.
Erythema
MedGen UID:
11999
Concept ID:
C0041834
Disease or Syndrome
Redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin.
Cataract
MedGen UID:
39462
Concept ID:
C0086543
Disease or Syndrome
A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMEDNIK syndrome
Follow this link to review classifications for MEDNIK syndrome in Orphanet.

Recent clinical studies

Diagnosis

Lu JG, Namjoshi SS, Niehaus AD, Tahata S, Lee CU, Wang L, McDonnell E, Seely M, Martin MG, Hazard FK
Pediatr Dev Pathol 2023 Jul-Aug;26(4):406-410. Epub 2023 Jun 6 doi: 10.1177/10935266231177402. PMID: 37278357
Klee KMC, Janecke AR, Civan HA, Rosipal Š, Heinz-Erian P, Huber LA, Müller T, Vogel GF
Hum Genet 2020 Oct;139(10):1247-1259. Epub 2020 Apr 18 doi: 10.1007/s00439-020-02168-w. PMID: 32306098Free PMC Article
Overeem AW, Klappe K, Parisi S, Klöters-Planchy P, Mataković L, du Teil Espina M, Drouin CA, Weiss KH, van IJzendoorn SCD
J Hepatol 2019 Aug;71(2):344-356. Epub 2019 Apr 6 doi: 10.1016/j.jhep.2019.03.031. PMID: 30965071
Incecik F, Bisgin A, Yılmaz M
Metab Brain Dis 2018 Dec;33(6):2065-2068. Epub 2018 Sep 23 doi: 10.1007/s11011-018-0313-4. PMID: 30244301
Kaler SG
Handb Clin Neurol 2013;113:1745-54. doi: 10.1016/B978-0-444-59565-2.00045-9. PMID: 23622398Free PMC Article

Therapy

Martinelli D, Dionisi-Vici C
Ann N Y Acad Sci 2014 May;1314:55-63. Epub 2014 Apr 22 doi: 10.1111/nyas.12426. PMID: 24754424
Kaler SG
Handb Clin Neurol 2013;113:1745-54. doi: 10.1016/B978-0-444-59565-2.00045-9. PMID: 23622398Free PMC Article
Martinelli D, Travaglini L, Drouin CA, Ceballos-Picot I, Rizza T, Bertini E, Carrozzo R, Petrini S, de Lonlay P, El Hachem M, Hubert L, Montpetit A, Torre G, Dionisi-Vici C
Brain 2013 Mar;136(Pt 3):872-81. Epub 2013 Feb 18 doi: 10.1093/brain/awt012. PMID: 23423674

Prognosis

Rackova M, Mattera R, Svaton M, Fencl F, Kanderova V, Spicakova K, Park SY, Fabian O, Koblizek M, Fronkova E, Bonifacino JS, Skvarova Kramarzova K
J Mol Med (Berl) 2024 Nov;102(11):1343-1353. Epub 2024 Sep 13 doi: 10.1007/s00109-024-02482-0. PMID: 39269494Free PMC Article
Incecik F, Bisgin A, Yılmaz M
Metab Brain Dis 2018 Dec;33(6):2065-2068. Epub 2018 Sep 23 doi: 10.1007/s11011-018-0313-4. PMID: 30244301
Kaler SG
Handb Clin Neurol 2013;113:1745-54. doi: 10.1016/B978-0-444-59565-2.00045-9. PMID: 23622398Free PMC Article

Clinical prediction guides

Rackova M, Mattera R, Svaton M, Fencl F, Kanderova V, Spicakova K, Park SY, Fabian O, Koblizek M, Fronkova E, Bonifacino JS, Skvarova Kramarzova K
J Mol Med (Berl) 2024 Nov;102(11):1343-1353. Epub 2024 Sep 13 doi: 10.1007/s00109-024-02482-0. PMID: 39269494Free PMC Article
Klee KMC, Janecke AR, Civan HA, Rosipal Š, Heinz-Erian P, Huber LA, Müller T, Vogel GF
Hum Genet 2020 Oct;139(10):1247-1259. Epub 2020 Apr 18 doi: 10.1007/s00439-020-02168-w. PMID: 32306098Free PMC Article
Incecik F, Bisgin A, Yılmaz M
Metab Brain Dis 2018 Dec;33(6):2065-2068. Epub 2018 Sep 23 doi: 10.1007/s11011-018-0313-4. PMID: 30244301
Bonnemaison ML, Bäck N, Duffy ME, Ralle M, Mains RE, Eipper BA
J Biol Chem 2015 Aug 28;290(35):21264-79. Epub 2015 Jul 13 doi: 10.1074/jbc.M115.641027. PMID: 26170456Free PMC Article
Puri PK, Reddi DM, Spencer-Manzon M, Deak K, Steele SU, Mikati MA
Arch Dermatol 2012 Jan;148(1):73-8. Epub 2011 Sep 19 doi: 10.1001/archdermatol.2011.281. PMID: 21931015

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