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3p- syndrome

MedGen UID:
1643555
Concept ID:
C4706503
Disease or Syndrome
Synonyms: 3p deletion syndrome; Chromosome 3, deletion 3p; Chromosome 3, monosomy 3p; Chromosome 3, monosomy 3p25; Chromosome 3pter-p25 deletion syndrome; Del(3p) syndrome; Deletion 3p; Deletion 3p25; Monosomy 3p
SNOMED CT: Distal monosomy 3p syndrome (763528002); Distal 3p deletion (763528002); Distal monosomy 3p (763528002); 3p syndrome (763528002)
 
Monarch Initiative: MONDO:0013424
OMIM®: 613792
Orphanet: ORPHA1620

Definition

Characteristic features of the distal 3p- syndrome include low birth weight, microcephaly, trigonocephaly, hypotonia, psychomotor and growth retardation, ptosis, telecanthus, downslanting palpebral fissures, and micrognathia. Postaxial polydactyly, renal anomalies, cleft palate, congenital heart defects (especially atrioventricular septal defects), preauricular pits, sacral dimple, and gastrointestinal anomalies are variable features. Although intellectual deficits are almost invariably associated with cytogenetically visible 3p deletions, rare patients with a 3p26-p25 deletion and normal intelligence or only mild abnormalities have been described (summary by Shuib et al., 2009). [from OMIM]

Additional description

From MedlinePlus Genetics
3p deletion syndrome is a condition that results from a chromosomal change in which a small piece of chromosome 3 is deleted in each cell. The deletion occurs at the end of the short (p) arm of the chromosome. This chromosomal change often leads to intellectual disability, developmental delay, and abnormal physical features.

Individuals with 3p deletion syndrome typically have severe to profound intellectual disability. Most have delayed development of language skills as well as motor skills such as crawling and walking. While affected individuals learn to walk in childhood, their language ability usually remains limited. Some individuals with 3p deletion syndrome have obsessive-compulsive disorder (OCD) or features of autism spectrum disorders, which are conditions characterized by impaired communication and social interaction.

The physical signs and symptoms of 3p deletion syndrome vary greatly. Many affected individuals have slow growth, an abnormally small head (microcephaly), a small jaw (micrognathia), droopy eyelids (ptosis), malformed ears or nose, and widely spaced eyes (hypertelorism). Other frequent features include skin folds covering the inner corner of the eyes (epicanthal folds), extra fingers or toes (polydactyly), and an opening in the roof of the mouth (cleft palate). Additionally, individuals with 3p deletion syndrome may have seizures, weak muscle tone (hypotonia), intestinal abnormalities, or congenital heart defects.  https://medlineplus.gov/genetics/condition/3p-deletion-syndrome

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Abnormal renal morphology
MedGen UID:
1633142
Concept ID:
C4551596
Anatomical Abnormality
Any structural anomaly of the kidney.
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.
Tapered finger
MedGen UID:
98098
Concept ID:
C0426886
Finding
The gradual reduction in girth of the finger from proximal to distal.
Overlapping toe
MedGen UID:
182531
Concept ID:
C0920299
Anatomical Abnormality
Describes a foot digit resting on the dorsal surface of an adjacent digit when the foot is at rest. Initially clawing may be dynamic and only noticeable on walking. Over time the plantar plate tears, subluxation occurs at the metatarsophalangeal joint (MTPJ), and the deformity becomes permanent.
Atrioventricular canal defect
MedGen UID:
235591
Concept ID:
C1389016
Anatomical Abnormality
A defect of the atrioventricular septum of the heart.
Abnormal cardiovascular system morphology
MedGen UID:
892473
Concept ID:
C4049796
Anatomical Abnormality
Any structural anomaly of the heart and blood vessels.
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.
Small for gestational age
MedGen UID:
65920
Concept ID:
C0235991
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the 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).
Growth delay
MedGen UID:
99124
Concept ID:
C0456070
Pathologic Function
A deficiency or slowing down of growth pre- and postnatally.
Postnatal growth retardation
MedGen UID:
395343
Concept ID:
C1859778
Finding
Slow or limited growth after birth.
Imperforate anus
MedGen UID:
1997
Concept ID:
C0003466
Congenital Abnormality
Congenital absence of the anus, i.e., the opening at the bottom end of the intestinal tract.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Gastroesophageal reflux
MedGen UID:
1368658
Concept ID:
C4317146
Finding
A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Overfolded helix
MedGen UID:
325239
Concept ID:
C1837731
Finding
A condition in which the helix is folded over to a greater degree than normal. That is, excessive curling of the helix edge, whereby the free edge is parallel to the plane of the ear.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
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.
EEG abnormality
MedGen UID:
56235
Concept ID:
C0151611
Finding
Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp.
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.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
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.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
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.
Retrognathia
MedGen UID:
19766
Concept ID:
C0035353
Congenital Abnormality
An abnormality in which the mandible is mislocalised posteriorly.
Brachycephaly
MedGen UID:
113165
Concept ID:
C0221356
Congenital Abnormality
An abnormality of skull shape characterized by a decreased anterior-posterior diameter. That is, a cephalic index greater than 81%. Alternatively, an apparently shortened anteroposterior dimension (length) of the head compared to width.
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.
Trigonocephaly
MedGen UID:
82713
Concept ID:
C0265535
Congenital Abnormality
Wedge-shaped, or triangular head, with the apex of the triangle at the midline of the forehead and the base of the triangle at the occiput.
Flat occiput
MedGen UID:
332439
Concept ID:
C1837402
Finding
Reduced convexity of the occiput (posterior part of skull).
Prominent metopic ridge
MedGen UID:
387953
Concept ID:
C1857949
Finding
Vertical bony ridge positioned in the midline of the forehead.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Blepharophimosis
MedGen UID:
2670
Concept ID:
C0005744
Anatomical Abnormality
A fixed reduction in the vertical distance between the upper and lower eyelids with short palpebral fissures.
Bulbous nose
MedGen UID:
66013
Concept ID:
C0240543
Finding
Increased volume and globular shape of the anteroinferior aspect of the nose.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
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.
Broad nasal tip
MedGen UID:
98424
Concept ID:
C0426429
Finding
Increase in width of the nasal tip.
Thin vermilion border
MedGen UID:
108294
Concept ID:
C0578038
Finding
Height of the vermilion of the medial part of the lip more than 2 SD below the mean, or apparently reduced height of the vermilion of the lip in the frontal view. The vermilion is the red part of the lips (and confusingly, the vermilion itself is also often referred to as being equivalent the lips).
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).
Triangular face
MedGen UID:
324383
Concept ID:
C1835884
Finding
Facial contour, as viewed from the front, triangular in shape, with breadth at the temples and tapering to a narrow chin.
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Anteverted nares
MedGen UID:
326648
Concept ID:
C1840077
Finding
Anteriorly-facing nostrils viewed with the head in the Frankfurt horizontal and the eyes of the observer level with the eyes of the subject. This gives the appearance of an upturned nose (upturned nasal tip).
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Prominent nasal bridge
MedGen UID:
343051
Concept ID:
C1854113
Finding
Anterior positioning of the nasal root in comparison to the usual positioning for age.
Low hanging columella
MedGen UID:
344656
Concept ID:
C1856119
Finding
Columella extending inferior to the level of the nasal base, when viewed from the side.
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.
Thin upper lip vermilion
MedGen UID:
355352
Concept ID:
C1865017
Finding
Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective).
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.
Highly arched eyebrow
MedGen UID:
358357
Concept ID:
C1868571
Finding
Increased height of the central portion of the eyebrow, forming a crescent, semicircular, or inverted U shape.
Periorbital fullness
MedGen UID:
1710990
Concept ID:
C4760994
Finding
Increase in periorbital soft tissue.
Preauricular pit
MedGen UID:
120587
Concept ID:
C0266610
Congenital Abnormality
Small indentation anterior to the insertion of the ear.
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.
Synophrys
MedGen UID:
98132
Concept ID:
C0431447
Congenital Abnormality
Meeting of the medial eyebrows in the midline.
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).
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).
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.
Macular hypoplasia
MedGen UID:
340322
Concept ID:
C1849412
Finding
Underdevelopment of the macula lutea.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGV3p- syndrome

Professional guidelines

PubMed

Hausvater A, Spruill TM, Xia Y, Smilowitz NR, Arabadjian M, Shah B, Park K, Giesler C, Marzo K, Thomas D, Wei J, Trost J, Mehta PK, Har B, Bainey KR, Zhong H, Hochman JS, Reynolds HR
J Am Coll Cardiol 2023 Oct 24;82(17):1649-1658. doi: 10.1016/j.jacc.2023.08.028. PMID: 37852694Free PMC Article
Akpek EK, Wirta DL, Downing JE, Tauber J, Sheppard JD, Ciolino JB, Meides AS, Krösser S
JAMA Ophthalmol 2023 May 1;141(5):459-466. doi: 10.1001/jamaophthalmol.2023.0709. PMID: 37022717Free PMC Article
Adrogué HJ, Tucker BM, Madias NE
JAMA 2022 Jul 19;328(3):280-291. doi: 10.1001/jama.2022.11176. PMID: 35852524

Recent clinical studies

Etiology

Lu S, Wei X, Chen B, Chen J, Zhang L, Yang M, Sun Z, Shi Y, Kong Y, Liu S, Li Y
Acta Otolaryngol 2021 Jun;141(6):551-556. Epub 2021 Apr 5 doi: 10.1080/00016489.2021.1906947. PMID: 33819124
Dikow N, Maas B, Karch S, Granzow M, Janssen JW, Jauch A, Hinderhofer K, Sutter C, Schubert-Bast S, Anderlid BM, Dallapiccola B, Van der Aa N, Moog U
Am J Med Genet A 2014 Dec;164A(12):3061-8. Epub 2014 Sep 24 doi: 10.1002/ajmg.a.36761. PMID: 25256099
Verloes A, Bremond-Gignac D, Isidor B, David A, Baumann C, Leroy MA, Stevens R, Gillerot Y, Héron D, Héron B, Benzacken B, Lacombe D, Brunner H, Bitoun P
Am J Med Genet A 2006 Jun 15;140(12):1285-96. doi: 10.1002/ajmg.a.31270. PMID: 16700052
Phipps ME, Latif F, Prowse A, Payne SJ, Dietz-Band J, Leversha M, Affara NA, Moore AT, Tolmie J, Schinzel A
Hum Mol Genet 1994 Jun;3(6):903-8. doi: 10.1093/hmg/3.6.903. PMID: 7951234
Charrow J, Cohen MM, Meeker D
Am J Med Genet 1981;8(4):431-6. doi: 10.1002/ajmg.1320080408. PMID: 7246613

Diagnosis

Alzahrani AS, Bin Nafisah A, Alswailem M, Moria Y, Poprawski D, Al-Hindi H, Pacak K
Front Endocrinol (Lausanne) 2023;14:1273093. Epub 2023 Dec 13 doi: 10.3389/fendo.2023.1273093. PMID: 38152133Free PMC Article
Lu S, Wei X, Chen B, Chen J, Zhang L, Yang M, Sun Z, Shi Y, Kong Y, Liu S, Li Y
Acta Otolaryngol 2021 Jun;141(6):551-556. Epub 2021 Apr 5 doi: 10.1080/00016489.2021.1906947. PMID: 33819124
Verloes A, Bremond-Gignac D, Isidor B, David A, Baumann C, Leroy MA, Stevens R, Gillerot Y, Héron D, Héron B, Benzacken B, Lacombe D, Brunner H, Bitoun P
Am J Med Genet A 2006 Jun 15;140(12):1285-96. doi: 10.1002/ajmg.a.31270. PMID: 16700052
Jenderny J, Poetsch M, Hoeltzenbein M, Friedrich U, Jauch A
Eur J Hum Genet 1998 Sep-Oct;6(5):439-44. doi: 10.1038/sj.ejhg.5200217. PMID: 9801868
Knight LA, Yong MH, Tan M, Ng IS
J Med Genet 1995 Dec;32(12):994-5. doi: 10.1136/jmg.32.12.994. PMID: 8825934Free PMC Article

Therapy

Alzahrani AS, Bin Nafisah A, Alswailem M, Moria Y, Poprawski D, Al-Hindi H, Pacak K
Front Endocrinol (Lausanne) 2023;14:1273093. Epub 2023 Dec 13 doi: 10.3389/fendo.2023.1273093. PMID: 38152133Free PMC Article
Phipps ME, Latif F, Prowse A, Payne SJ, Dietz-Band J, Leversha M, Affara NA, Moore AT, Tolmie J, Schinzel A
Hum Mol Genet 1994 Jun;3(6):903-8. doi: 10.1093/hmg/3.6.903. PMID: 7951234

Prognosis

Verloes A, Bremond-Gignac D, Isidor B, David A, Baumann C, Leroy MA, Stevens R, Gillerot Y, Héron D, Héron B, Benzacken B, Lacombe D, Brunner H, Bitoun P
Am J Med Genet A 2006 Jun 15;140(12):1285-96. doi: 10.1002/ajmg.a.31270. PMID: 16700052
Phipps ME, Latif F, Prowse A, Payne SJ, Dietz-Band J, Leversha M, Affara NA, Moore AT, Tolmie J, Schinzel A
Hum Mol Genet 1994 Jun;3(6):903-8. doi: 10.1093/hmg/3.6.903. PMID: 7951234
Charrow J, Cohen MM, Meeker D
Am J Med Genet 1981;8(4):431-6. doi: 10.1002/ajmg.1320080408. PMID: 7246613

Clinical prediction guides

Dijkhuizen T, van Essen T, van der Vlies P, Verheij JB, Sikkema-Raddatz B, van der Veen AY, Gerssen-Schoorl KB, Buys CH, Kok K
Am J Med Genet A 2006 Nov 15;140(22):2482-7. doi: 10.1002/ajmg.a.31487. PMID: 17036314
Drumheller T, McGillivray BC, Behrner D, MacLeod P, McFadden DE, Roberson J, Venditti C, Chorney K, Chorney M, Smith DI
J Med Genet 1996 Oct;33(10):842-7. doi: 10.1136/jmg.33.10.842. PMID: 8933338Free PMC Article
Knight LA, Yong MH, Tan M, Ng IS
J Med Genet 1995 Dec;32(12):994-5. doi: 10.1136/jmg.32.12.994. PMID: 8825934Free PMC Article
Charrow J, Cohen MM, Meeker D
Am J Med Genet 1981;8(4):431-6. doi: 10.1002/ajmg.1320080408. PMID: 7246613

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