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Microcephaly, short stature, and limb abnormalities(MISSLA)

MedGen UID:
1613834
Concept ID:
C4539873
Disease or Syndrome
Synonyms: MICROCEPHALY, SHORT STATURE, AND LIMB ABNORMALITIES; MISSLA
 
Gene (location): DONSON (21q22.11)
 
Monarch Initiative: MONDO:0060533
OMIM®: 617604
Orphanet: ORPHA572773

Definition

MISSLA is an autosomal recessive disorder characterized by intrauterine growth retardation, microcephaly, variable short stature, and limb abnormalities mainly affecting the upper limb and radial ray. Affected individuals typically have mild intellectual disability, but may have normal development (summary by Reynolds et al., 2017). [from OMIM]

Clinical features

From HPO
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Dislocated radial head
MedGen UID:
488814
Concept ID:
C0265563
Congenital Abnormality
A dislocation of the head of the radius from its socket in the elbow joint.
Mesomelia
MedGen UID:
107808
Concept ID:
C0549306
Congenital Abnormality
Shortening of the middle parts of the limbs (forearm and lower leg) in relation to the upper and terminal segments.
Hypoplasia of the radius
MedGen UID:
672334
Concept ID:
C0685381
Congenital Abnormality
Underdevelopment of the radius.
Short metacarpal
MedGen UID:
323064
Concept ID:
C1837084
Anatomical Abnormality
Diminished length of one or more metacarpal bones in relation to the others of the same hand or to the contralateral metacarpal.
Clinodactyly of the 5th finger
MedGen UID:
340456
Concept ID:
C1850049
Congenital Abnormality
Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger).
Patellar aplasia
MedGen UID:
401474
Concept ID:
C1868578
Congenital Abnormality
Absence of the patella.
Fetal growth restriction
MedGen UID:
4693
Concept ID:
C0015934
Pathologic Function
An abnormal restriction of fetal growth with fetal weight below the tenth percentile for gestational age.
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).
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.
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.
Simplified gyral pattern
MedGen UID:
413664
Concept ID:
C2749675
Finding
An abnormality of the cerebral cortex with fewer gyri but with normal cortical thickness. This pattern is usually often associated with congenital microcephaly.
Radioulnar synostosis
MedGen UID:
57861
Concept ID:
C0158761
Congenital Abnormality
An abnormal osseous union (fusion) between the radius and the ulna.
Delayed skeletal maturation
MedGen UID:
108148
Concept ID:
C0541764
Finding
A decreased rate of skeletal maturation. Delayed skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Abnormal rib morphology
MedGen UID:
330763
Concept ID:
C1842083
Anatomical Abnormality
An anomaly of the rib.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Convex nasal ridge
MedGen UID:
66809
Concept ID:
C0240538
Finding
Nasal ridge curving anteriorly to an imaginary line that connects the nasal root and tip. The nose appears often also prominent, and the columella low.
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.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVMicrocephaly, short stature, and limb abnormalities

Professional guidelines

PubMed

Han J, Yang YD, He Y, Liu WJ, Zhen L, Pan M, Yang X, Zhang VW, Liao C, Li DZ
Prenat Diagn 2020 Apr;40(5):577-584. Epub 2020 Feb 10 doi: 10.1002/pd.5653. PMID: 31994750

Recent clinical studies

Etiology

Luk HM, Yeung KS, Wong WL, Chung BH, Tong TM, Lo IF
Hong Kong Med J 2016 Dec;22(6):526-33. Epub 2016 Jul 29 doi: 10.12809/hkmj154750. PMID: 27468965
Ganjavi H, Siu VM, Speevak M, MacDonald PA
BMJ Case Rep 2014 Nov 12;2014 doi: 10.1136/bcr-2014-207501. PMID: 25391829Free PMC Article
Beets L, Rodríguez-Fonseca C, Hennekam RC
Am J Med Genet A 2014 Sep;164A(9):2300-9. Epub 2014 Jul 2 doi: 10.1002/ajmg.a.36654. PMID: 24989455
Willems M, Geneviève D, Borck G, Baumann C, Baujat G, Bieth E, Edery P, Farra C, Gerard M, Héron D, Leheup B, Le Merrer M, Lyonnet S, Martin-Coignard D, Mathieu M, Thauvin-Robinet C, Verloes A, Colleaux L, Munnich A, Cormier-Daire V
J Med Genet 2010 Dec;47(12):797-802. Epub 2009 Jul 29 doi: 10.1136/jmg.2009.067298. PMID: 19643772
Wulfsberg EA, Campbell AB, Lurie IW, Eanet KR
Am J Med Genet 1996 Jun 28;63(4):554-7. doi: 10.1002/(SICI)1096-8628(19960628)63:4<554::AID-AJMG8>3.0.CO;2-O. PMID: 8826434

Diagnosis

Enomoto Y, Tsurusaki Y, Yokoi T, Abe-Hatano C, Ida K, Naruto T, Mitsui J, Tsuji S, Morishita S, Kurosawa K
Eur J Med Genet 2020 Jan;63(1):103610. Epub 2018 Dec 30 doi: 10.1016/j.ejmg.2018.12.015. PMID: 30602132
Karaca E, Posey JE, Bostwick B, Liu P, Gezdirici A, Yesil G, Coban Akdemir Z, Bayram Y, Harms FL, Meinecke P, Alawi M, Bacino CA, Sutton VR, Kortüm F, Lupski JR
Am J Med Genet A 2019 Oct;179(10):2056-2066. Epub 2019 Aug 13 doi: 10.1002/ajmg.a.61315. PMID: 31407851Free PMC Article
Luk HM, Yeung KS, Wong WL, Chung BH, Tong TM, Lo IF
Hong Kong Med J 2016 Dec;22(6):526-33. Epub 2016 Jul 29 doi: 10.12809/hkmj154750. PMID: 27468965
Ganjavi H, Siu VM, Speevak M, MacDonald PA
BMJ Case Rep 2014 Nov 12;2014 doi: 10.1136/bcr-2014-207501. PMID: 25391829Free PMC Article
Ravel A, Chouery E, Stora S, Jalkh N, Villard L, Temtamy S, Mégarbané A
Am J Med Genet A 2011 Apr;155A(4):880-4. Epub 2011 Mar 17 doi: 10.1002/ajmg.a.33879. PMID: 21416592

Therapy

Ganjavi H, Siu VM, Speevak M, MacDonald PA
BMJ Case Rep 2014 Nov 12;2014 doi: 10.1136/bcr-2014-207501. PMID: 25391829Free PMC Article
Zlotogora J, Dagan J, Ganen A, Abu-Libdeh M, Ben-Neriah Z, Cohen T
J Med Genet 1997 Oct;34(10):813-6. doi: 10.1136/jmg.34.10.813. PMID: 9350812Free PMC Article

Prognosis

Zorn M, Kühnisch J, Bachmann S, Seifert W
Sci Rep 2022 Jun 11;12(1):9686. doi: 10.1038/s41598-022-13717-w. PMID: 35690661Free PMC Article
Kantaputra PN, Dejkhamron P, Intachai W, Ngamphiw C, Kawasaki K, Ohazama A, Krisanaprakornkit S, Olsen B, Tongsima S, Ketudat Cairns JR
Eur J Orthod 2021 Jan 29;43(1):45-50. doi: 10.1093/ejo/cjaa023. PMID: 32255174
Grote LE, Repnikova EA, Amudhavalli SM
Am J Med Genet A 2015 Dec;167A(12):3219-25. Epub 2015 Sep 11 doi: 10.1002/ajmg.a.37368. PMID: 26360630
Mumtaz S, Yıldız E, Jabeen S, Khan A, Tolun A, Malik S
Am J Med Genet A 2015 Dec;167A(12):3148-52. Epub 2015 Sep 3 doi: 10.1002/ajmg.a.37299. PMID: 26333564
Ganjavi H, Siu VM, Speevak M, MacDonald PA
BMJ Case Rep 2014 Nov 12;2014 doi: 10.1136/bcr-2014-207501. PMID: 25391829Free PMC Article

Clinical prediction guides

Zorn M, Kühnisch J, Bachmann S, Seifert W
Sci Rep 2022 Jun 11;12(1):9686. doi: 10.1038/s41598-022-13717-w. PMID: 35690661Free PMC Article
Kantaputra PN, Dejkhamron P, Intachai W, Ngamphiw C, Kawasaki K, Ohazama A, Krisanaprakornkit S, Olsen B, Tongsima S, Ketudat Cairns JR
Eur J Orthod 2021 Jan 29;43(1):45-50. doi: 10.1093/ejo/cjaa023. PMID: 32255174
Karaca E, Posey JE, Bostwick B, Liu P, Gezdirici A, Yesil G, Coban Akdemir Z, Bayram Y, Harms FL, Meinecke P, Alawi M, Bacino CA, Sutton VR, Kortüm F, Lupski JR
Am J Med Genet A 2019 Oct;179(10):2056-2066. Epub 2019 Aug 13 doi: 10.1002/ajmg.a.61315. PMID: 31407851Free PMC Article
Luk HM, Yeung KS, Wong WL, Chung BH, Tong TM, Lo IF
Hong Kong Med J 2016 Dec;22(6):526-33. Epub 2016 Jul 29 doi: 10.12809/hkmj154750. PMID: 27468965
Frydman M, Katz M, Cabot SG, Soen G, Kauschansky A, Sirota L
Am J Med Genet 1997 Aug 22;71(3):251-7. doi: 10.1002/(sici)1096-8628(19970822)71:3<251::aid-ajmg1>3.0.co;2-x. PMID: 9268091

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