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Chromosome 4q21 deletion syndrome

MedGen UID:
462106
Concept ID:
C3150756
Disease or Syndrome
Synonym: CHROMOSOME 4q21 DELETION SYNDROME
Modes of inheritance:
Unknown inheritance
MedGen UID:
989040
Concept ID:
CN307042
Finding
Source: Orphanet
Hereditary clinical entity whose mode of inheritance is unknown.
Not genetically inherited
MedGen UID:
988794
Concept ID:
CN307044
Finding
Source: Orphanet
clinical entity without genetic inheritance.
 
Monarch Initiative: MONDO:0013292
OMIM®: 613509
Orphanet: ORPHA238750

Definition

The 4q21 microdeletion syndrome is a newly described syndrome associated with facial dysmorphism, progressive growth restriction, severe intellectual deficit and absent or severely delayed speech. [from ORDO]

Clinical features

From HPO
Severe short stature
MedGen UID:
3931
Concept ID:
C0013336
Disease or Syndrome
A severe degree of short stature, more than -4 SD from the mean corrected for age and sex.
Postnatal growth retardation
MedGen UID:
395343
Concept ID:
C1859778
Finding
Slow or limited growth after birth.
Sensorineural hearing impairment
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.
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.
Cerebral hypoplasia
MedGen UID:
343321
Concept ID:
C1855330
Finding
Underdevelopment of the cerebrum.
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.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Dolichocephaly
MedGen UID:
65142
Concept ID:
C0221358
Congenital Abnormality
An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture.
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.
Narrow mouth
MedGen UID:
44435
Concept ID:
C0026034
Congenital Abnormality
Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective).
Broad forehead
MedGen UID:
338610
Concept ID:
C1849089
Finding
Width of the forehead or distance between the frontotemporales is more than two standard deviations above the mean (objective); or apparently increased distance between the two sides of the forehead.
Short philtrum
MedGen UID:
350006
Concept ID:
C1861324
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD below the mean. Alternatively, an apparently decreased distance between nasal base and midline upper lip vermilion border.
Long philtrum
MedGen UID:
351278
Concept ID:
C1865014
Finding
Distance between nasal base and midline upper lip vermilion border more than 2 SD above the mean. Alternatively, an apparently increased distance between nasal base and midline upper lip vermilion border.
Downturned corners of mouth
MedGen UID:
356471
Concept ID:
C1866195
Anatomical Abnormality
A morphological abnormality of the mouth in which the angle of the mouth is downturned. The oral commissures are positioned inferior to the midline labial fissure.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVChromosome 4q21 deletion syndrome
Follow this link to review classifications for Chromosome 4q21 deletion syndrome in Orphanet.

Recent clinical studies

Etiology

Cameron F, Xu J, Jung J, Prasad C
Can J Neurol Sci 2013 Nov;40(6):777-82. doi: 10.1017/s0317167100015882. PMID: 24257216
Wiśniowiecka-Kowalnik B, Kastory-Bronowska M, Bartnik M, Derwińska K, Dymczak-Domini W, Szumbarska D, Ziemka E, Szczałuba K, Sykulski M, Gambin T, Gambin A, Shaw CA, Mazurczak T, Obersztyn E, Bocian E, Stankiewicz P
Eur J Hum Genet 2013 Jun;21(6):620-5. Epub 2012 Oct 3 doi: 10.1038/ejhg.2012.219. PMID: 23032108Free PMC Article
Jones AC, Yamamura Y, Almasy L, Bohlega S, Elibol B, Hubble J, Kuzuhara S, Uchida M, Yanagi T, Weeks DE, Nygaard TG
Am J Hum Genet 1998 Jul;63(1):80-7. doi: 10.1086/301937. PMID: 9634534Free PMC Article

Diagnosis

Giguet-Valard AG, Thevenin C, Dreux S, Decatrelle V, Juve ML, Yazza S, Adenet C, Lesueur M, Bouvagnet P, Gueneret M
Mol Genet Genomic Med 2024 Feb;12(2):e2397. doi: 10.1002/mgg3.2397. PMID: 38351708Free PMC Article
Hu X, Chen X, Wu B, Soler IM, Chen S, Shen Y
Am J Med Genet A 2017 Jan;173(1):120-125. Epub 2016 Sep 8 doi: 10.1002/ajmg.a.37965. PMID: 27604828
Cameron F, Xu J, Jung J, Prasad C
Can J Neurol Sci 2013 Nov;40(6):777-82. doi: 10.1017/s0317167100015882. PMID: 24257216
Bhoj E, Halbach S, McDonald-McGinn D, Tan C, Lande R, Waggoner D, Zackai E
Am J Med Genet A 2013 Sep;161A(9):2327-33. Epub 2013 Aug 2 doi: 10.1002/ajmg.a.36061. PMID: 23913759
Lipska BS, Brzeskwiniewicz M, Wierzba J, Morzuchi L, Piotrowski A, Limon J
Genet Couns 2011;22(4):353-63. PMID: 22303795

Therapy

Martínez F, Tomás M, Millán JM, Fernández A, Palau F, Prieto F
J Med Genet 1998 Apr;35(4):284-7. doi: 10.1136/jmg.35.4.284. PMID: 9598720Free PMC Article

Prognosis

Maldžienė Ž, Vaitėnienė EM, Aleksiūnienė B, Utkus A, Preikšaitienė E
BMC Med Genomics 2020 Apr 16;13(1):63. doi: 10.1186/s12920-020-0711-4. PMID: 32299451Free PMC Article
Cameron F, Xu J, Jung J, Prasad C
Can J Neurol Sci 2013 Nov;40(6):777-82. doi: 10.1017/s0317167100015882. PMID: 24257216
Tsang E, Rupps R, McGillivray B, Eydoux P, Marra M, Arbour L, Langlois S, Friedman JM, Zahir FR
Am J Med Genet A 2012 Oct;158A(10):2606-9. Epub 2012 Aug 17 doi: 10.1002/ajmg.a.35568. PMID: 22903878
Giannikou K, Fryssira H, Oikonomakis V, Syrmou A, Kosma K, Tzetis M, Kitsiou-Tzeli S, Kanavakis E
Gene 2012 Sep 15;506(2):360-8. Epub 2012 Jul 2 doi: 10.1016/j.gene.2012.06.060. PMID: 22766398
Nowaczyk MJ, Teshima IE, Siegel-Bartelt J, Clarke JT
Am J Med Genet 1997 Apr 14;69(4):400-5. PMID: 9098490

Clinical prediction guides

Maldžienė Ž, Vaitėnienė EM, Aleksiūnienė B, Utkus A, Preikšaitienė E
BMC Med Genomics 2020 Apr 16;13(1):63. doi: 10.1186/s12920-020-0711-4. PMID: 32299451Free PMC Article
Li LL, Zhang HG, Shao XG, Gao JC, Zhang HY, Liu RZ
Genet Mol Res 2016 Jul 14;15(2) doi: 10.4238/gmr.15028403. PMID: 27421024
Lipska BS, Brzeskwiniewicz M, Wierzba J, Morzuchi L, Piotrowski A, Limon J
Genet Couns 2011;22(4):353-63. PMID: 22303795
Terada Y, Imoto I, Nagai H, Suwa K, Momoi M, Tajiri T, Onda M, Inazawa J, Emi M
Am J Med Genet 2001 Oct 1;103(2):176-80. doi: 10.1002/ajmg.1521. PMID: 11568928
Grimbacher B, Dutra AS, Holland SM, Fischer RE, Pao M, Gallin JI, Puck JM
Genet Med 1999 Jul-Aug;1(5):213-8. doi: 10.1097/00125817-199907000-00008. PMID: 11256675

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