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Meckel syndrome, type 10(MKS10)

MedGen UID:
481666
Concept ID:
C3280036
Disease or Syndrome
Synonyms: B9D2-Related Meckel Syndrome; MKS10
 
Gene (location): B9D2 (19q13.2)
 
Monarch Initiative: MONDO:0013609
OMIM®: 614175

Definition

Meckel syndrome is a disorder with severe signs and symptoms that affect many parts of the body. The most common features are enlarged kidneys with numerous fluid-filled cysts; an occipital encephalocele, which is a sac-like protrusion of the brain through an opening at the back of the skull; and the presence of extra fingers and toes (polydactyly). Most affected individuals also have a buildup of scar tissue (fibrosis) in the liver.

Because of their serious health problems, most individuals with Meckel syndrome die before or shortly after birth. Most often, affected infants die of respiratory problems or kidney failure.

Other signs and symptoms of Meckel syndrome vary widely among affected individuals. Numerous abnormalities of the brain and spinal cord (central nervous system) have been reported in people with Meckel syndrome, including a group of birth defects known as neural tube defects. These defects occur when a structure called the neural tube, a layer of cells that ultimately develops into the brain and spinal cord, fails to close completely during the first few weeks of embryonic development. Meckel syndrome can also cause problems with development of the eyes and other facial features, heart, bones, urinary system, and genitalia. [from MedlinePlus Genetics]

Clinical features

From HPO
Hypospadias
MedGen UID:
163083
Concept ID:
C0848558
Congenital Abnormality
Abnormal position of urethral meatus on the ventral penile shaft (underside) characterized by displacement of the urethral meatus from the tip of the glans penis to the ventral surface of the penis, scrotum, or perineum.
Renal cyst
MedGen UID:
854361
Concept ID:
C3887499
Disease or Syndrome
A fluid filled sac in the kidney.
Micropenis
MedGen UID:
1633603
Concept ID:
C4551492
Congenital Abnormality
Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.
Postaxial polydactyly
MedGen UID:
67394
Concept ID:
C0220697
Congenital Abnormality
Polydactyly refers to the occurrence of supernumerary digits and is the most frequent of congenital hand and foot deformities. Based on the location of the extra digits, polydactyly can be classified into preaxial, involving the thumb or great toe; postaxial, affecting the fifth digit; and central, involving the 3 central digits. Postaxial polydactyly (PAP) is further subclassified into 2 types: in type A, a well-formed extra digit articulates with the fifth or a sixth metacarpal, whereas in type B, a rudimentary, poorly developed extra digit is present (summary by Umm-e-Kalsoom et al., 2012). Genetic Heterogeneity of Postaxial Polydactyly Other forms of postaxial polydactyly type A include PAPA2 (602085) on chromosome 13q21; PAPA3 (607324) on chromosome 19p13; PAPA4 (608562) on chromosome 7q22; PAPA5 (263450) on chromosome 13q13; PAPA6 (615226), caused by mutation in the ZNF141 gene (194648) on chromosome 4p16; PAPA7 (617642), caused by mutation in the IQCE gene (617631) on chromosome 7p22; PAPA8 (618123), caused by mutation in the GLI1 gene (165220) on chromosome 12q13; PAPA9 (618219), caused by mutation in the CIBAR1 gene (617273) on chromosome 8q22; and PAPA10 (618498), caused by mutation in the KIAA0825 gene (617266) on chromosome 5q15.
Ulnar deviation of the hand
MedGen UID:
66031
Concept ID:
C0241521
Finding
Divergence of the longitudinal axis of the hand at the wrist in a posterior (ulnar) direction (i.e., towards the little finger).
Postaxial hand polydactyly
MedGen UID:
609221
Concept ID:
C0431904
Congenital Abnormality
Supernumerary digits located at the ulnar side of the hand (that is, on the side with the fifth finger).
Postaxial foot polydactyly
MedGen UID:
384489
Concept ID:
C2112129
Finding
Polydactyly of the foot most commonly refers to the presence of six toes on one foot. Postaxial polydactyly affects the lateral ray and the duplication may range from a well-formed articulated digit to a rudimentary digit.
Malformation of the hepatic ductal plate
MedGen UID:
346605
Concept ID:
C1857519
Finding
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.
Anencephaly
MedGen UID:
8068
Concept ID:
C0002902
Congenital Abnormality
Anencephaly is a condition that prevents the normal development of the brain and the bones of the skull. This condition results when a structure called the neural tube fails to close during the first few weeks of embryonic development. The neural tube is a layer of cells that ultimately develops into the brain and spinal cord. Because anencephaly is caused by abnormalities of the neural tube, it is classified as a neural tube defect.\n\nBecause the neural tube fails to close properly, the developing brain and spinal cord are exposed to the amniotic fluid that surrounds the fetus in the womb. This exposure causes the nervous system tissue to break down (degenerate). As a result, people with anencephaly are missing large parts of the brain called the cerebrum and cerebellum. These brain regions are necessary for thinking, hearing, vision, emotion, and coordinating movement. The bones of the skull are also missing or incompletely formed.\n\nBecause these nervous system abnormalities are so severe, almost all babies with anencephaly die before birth or within a few hours or days after birth.
Occipital encephalocele
MedGen UID:
4935
Concept ID:
C0014067
Congenital Abnormality
A type of encephalocele (that is, a a protrusion of part of the cranial contents including brain tissue through a congenital opening in the cranium, typically covered with skin or mucous membrane) in the occipital region of the skull. Occipital encephalocele presents as a midline swelling over the occipital bone. It is usually covered with normal full-thickness scalp.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Cerebellar hypoplasia
MedGen UID:
120578
Concept ID:
C0266470
Congenital Abnormality
Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time.
Dilated fourth ventricle
MedGen UID:
376050
Concept ID:
C1847117
Finding
An abnormal dilatation of the fourth cerebral ventricle.
Molar tooth sign on MRI
MedGen UID:
400670
Concept ID:
C1865060
Finding
An abnormal appearance of the midbrain in axial magnetic resonance imaging in which the elongated superior cerebellar peduncles give the midbrain an appearance reminiscent of a molar or wisdom tooth.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Camptodactyly
MedGen UID:
195780
Concept ID:
C0685409
Congenital Abnormality
The distal interphalangeal joint and/or the proximal interphalangeal joint of the fingers or toes cannot be extended to 180 degrees by either active or passive extension.
Dandy-Walker malformation
MedGen UID:
419183
Concept ID:
C2931867
Congenital Abnormality
A congenital brain malformation typically characterized by incomplete formation of the cerebellar vermis, dilation of the fourth ventricle, and enlargement of the posterior fossa. In layman's terms, Dandy Walker malformation is a cyst in the cerebellum (typically symmetrical) that is involved with the fourth ventricle. This may interfere with the ability to drain cerebrospinal fluid from the brain, resulting in hydrocephalus. Dandy Walker cysts are formed during early embryonic development, while the brain forms. The cyst in the cerebellum typically has several blood vessels running through it connecting to the brain, thereby prohibiting surgical removal.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Narrow palpebral fissure
MedGen UID:
382506
Concept ID:
C2675021
Finding
Reduction in the vertical distance between the upper and lower eyelids.
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
Bifid uvula
MedGen UID:
1646931
Concept ID:
C4551488
Congenital Abnormality
Uvula separated into two parts most easily seen at the tip.
Sacral dimple
MedGen UID:
98428
Concept ID:
C0426848
Finding
A cutaneous indentation resulting from tethering of the skin to underlying structures (bone) of the intergluteal cleft.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).

Recent clinical studies

Etiology

Simonini C, Floeck A, Strizek B, Mueller A, Gembruch U, Geipel A
Arch Gynecol Obstet 2022 Jul;306(1):71-83. Epub 2021 Oct 1 doi: 10.1007/s00404-021-06265-7. PMID: 34596737Free PMC Article
Shaheen R, Shamseldin HE, Loucks CM, Seidahmed MZ, Ansari S, Ibrahim Khalil M, Al-Yacoub N, Davis EE, Mola NA, Szymanska K, Herridge W, Chudley AE, Chodirker BN, Schwartzentruber J, Majewski J, Katsanis N, Poizat C, Johnson CA, Parboosingh J, Boycott KM, Innes AM, Alkuraya FS
Am J Hum Genet 2014 Jan 2;94(1):73-9. Epub 2013 Dec 19 doi: 10.1016/j.ajhg.2013.11.010. PMID: 24360803Free PMC Article
Barker AR, Thomas R, Dawe HR
Organogenesis 2014 Jan 1;10(1):96-107. Epub 2013 Dec 9 doi: 10.4161/org.27375. PMID: 24322779Free PMC Article
Travaglini L, Brancati F, Silhavy J, Iannicelli M, Nickerson E, Elkhartoufi N, Scott E, Spencer E, Gabriel S, Thomas S, Ben-Zeev B, Bertini E, Boltshauser E, Chaouch M, Cilio MR, de Jong MM, Kayserili H, Ogur G, Poretti A, Signorini S, Uziel G, Zaki MS; International JSRD Study Group, Johnson C, Attié-Bitach T, Gleeson JG, Valente EM
Eur J Hum Genet 2013 Oct;21(10):1074-8. Epub 2013 Feb 6 doi: 10.1038/ejhg.2012.305. PMID: 23386033Free PMC Article
Risteli L, von Koskull H, Autio-Harmainen H, Risteli J
Clin Chim Acta 1985 Apr 30;147(3):283-90. doi: 10.1016/0009-8981(85)90211-6. PMID: 2581726

Diagnosis

Junior JHMF, Junior SP, Pustilnik HN, de Almeida Leão L, da Paz MGDS, Araujo TB, de Deus FOG, Alcântara T, Dourado JC, de Avellar LM
Childs Nerv Syst 2024 Jul;40(7):2161-2168. Epub 2024 Mar 9 doi: 10.1007/s00381-024-06346-3. PMID: 38459147
Simonini C, Floeck A, Strizek B, Mueller A, Gembruch U, Geipel A
Arch Gynecol Obstet 2022 Jul;306(1):71-83. Epub 2021 Oct 1 doi: 10.1007/s00404-021-06265-7. PMID: 34596737Free PMC Article
Bruechle NO, Steuernagel P, Zerres K, Kurth I, Eggermann T, Knopp C
Pediatr Nephrol 2017 Oct;32(10):1989-1992. Epub 2017 Jun 15 doi: 10.1007/s00467-017-3710-8. PMID: 28620746
Travaglini L, Brancati F, Silhavy J, Iannicelli M, Nickerson E, Elkhartoufi N, Scott E, Spencer E, Gabriel S, Thomas S, Ben-Zeev B, Bertini E, Boltshauser E, Chaouch M, Cilio MR, de Jong MM, Kayserili H, Ogur G, Poretti A, Signorini S, Uziel G, Zaki MS; International JSRD Study Group, Johnson C, Attié-Bitach T, Gleeson JG, Valente EM
Eur J Hum Genet 2013 Oct;21(10):1074-8. Epub 2013 Feb 6 doi: 10.1038/ejhg.2012.305. PMID: 23386033Free PMC Article
Risteli L, von Koskull H, Autio-Harmainen H, Risteli J
Clin Chim Acta 1985 Apr 30;147(3):283-90. doi: 10.1016/0009-8981(85)90211-6. PMID: 2581726

Prognosis

Junior JHMF, Junior SP, Pustilnik HN, de Almeida Leão L, da Paz MGDS, Araujo TB, de Deus FOG, Alcântara T, Dourado JC, de Avellar LM
Childs Nerv Syst 2024 Jul;40(7):2161-2168. Epub 2024 Mar 9 doi: 10.1007/s00381-024-06346-3. PMID: 38459147
Molin A, Benoist G, Jeanne-Pasquier C, Elkartoufi N, Litzer J, Decamp M, Gruchy N, Durand-Malbruny M, Begorre M, Attie-Bitach T, Leporrier N
Eur J Med Genet 2013 Oct;56(10):580-3. Epub 2013 Aug 15 doi: 10.1016/j.ejmg.2013.08.002. PMID: 23954617

Clinical prediction guides

Simonini C, Floeck A, Strizek B, Mueller A, Gembruch U, Geipel A
Arch Gynecol Obstet 2022 Jul;306(1):71-83. Epub 2021 Oct 1 doi: 10.1007/s00404-021-06265-7. PMID: 34596737Free PMC Article
Barker AR, Thomas R, Dawe HR
Organogenesis 2014 Jan 1;10(1):96-107. Epub 2013 Dec 9 doi: 10.4161/org.27375. PMID: 24322779Free PMC Article
Molin A, Benoist G, Jeanne-Pasquier C, Elkartoufi N, Litzer J, Decamp M, Gruchy N, Durand-Malbruny M, Begorre M, Attie-Bitach T, Leporrier N
Eur J Med Genet 2013 Oct;56(10):580-3. Epub 2013 Aug 15 doi: 10.1016/j.ejmg.2013.08.002. PMID: 23954617
Leightner AC, Hommerding CJ, Peng Y, Salisbury JL, Gainullin VG, Czarnecki PG, Sussman CR, Harris PC
Hum Mol Genet 2013 May 15;22(10):2024-40. Epub 2013 Feb 7 doi: 10.1093/hmg/ddt054. PMID: 23393159Free PMC Article
Travaglini L, Brancati F, Silhavy J, Iannicelli M, Nickerson E, Elkhartoufi N, Scott E, Spencer E, Gabriel S, Thomas S, Ben-Zeev B, Bertini E, Boltshauser E, Chaouch M, Cilio MR, de Jong MM, Kayserili H, Ogur G, Poretti A, Signorini S, Uziel G, Zaki MS; International JSRD Study Group, Johnson C, Attié-Bitach T, Gleeson JG, Valente EM
Eur J Hum Genet 2013 Oct;21(10):1074-8. Epub 2013 Feb 6 doi: 10.1038/ejhg.2012.305. PMID: 23386033Free PMC Article

Recent systematic reviews

Junior JHMF, Junior SP, Pustilnik HN, de Almeida Leão L, da Paz MGDS, Araujo TB, de Deus FOG, Alcântara T, Dourado JC, de Avellar LM
Childs Nerv Syst 2024 Jul;40(7):2161-2168. Epub 2024 Mar 9 doi: 10.1007/s00381-024-06346-3. PMID: 38459147