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3M syndrome 1(3M1)

MedGen UID:
395592
Concept ID:
C2678312
Disease or Syndrome
Synonyms: 3-M Syndrome, CUL7-Related; Three M syndrome 1
 
Gene (location): CUL7 (6p21.1)
 
Monarch Initiative: MONDO:0010117
OMIM®: 273750

Disease characteristics

Excerpted from the GeneReview: Three M Syndrome
Three M syndrome is characterized by severe pre- and postnatal growth deficiency (final height 5-6 SD below the mean; i.e., 120-130 cm), characteristic facies, and normal intelligence. Additional features of three M syndrome include short broad neck, prominent trapezii, deformed sternum, short thorax, square shoulders, winged scapulae, hyperlordosis, short fifth fingers, prominent heels, and loose joints. Males with three M syndrome have hypogonadism and occasionally hypospadias. [from GeneReviews]
Authors:
Melita Irving  |  Muriel Holder-Espinasse   view full author information

Clinical features

From HPO
Decreased testicular size
MedGen UID:
66027
Concept ID:
C0241355
Finding
Reduced volume of the testicle (the male gonad).
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.
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Scapular winging
MedGen UID:
66822
Concept ID:
C0240953
Anatomical Abnormality
Abnormal protrusion of the scapula away from the surface of the back.
Short 5th finger
MedGen UID:
334269
Concept ID:
C1842878
Congenital Abnormality
Hypoplasia (congenital reduction in size) of the fifth finger, also known as the little finger.
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).
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.
Spina bifida occulta
MedGen UID:
36380
Concept ID:
C0080174
Congenital Abnormality
The closed form of spina bifida with incomplete closure of a vertebral body with intact overlying skin.
Joint dislocation
MedGen UID:
41614
Concept ID:
C0012691
Injury or Poisoning
Displacement or malalignment of joints.
Hip dislocation
MedGen UID:
42455
Concept ID:
C0019554
Injury or Poisoning
Displacement of the femur from its normal location in the hip joint.
Hyperlordosis
MedGen UID:
9805
Concept ID:
C0024003
Finding
Abnormally increased curvature (anterior concavity) of the lumbar or cervical spine.
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.
Short thorax
MedGen UID:
140876
Concept ID:
C0426789
Finding
Reduced inferior to superior extent of the thorax.
Short ribs
MedGen UID:
98094
Concept ID:
C0426817
Finding
Reduced rib length.
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.
Slender long bone
MedGen UID:
331446
Concept ID:
C1833144
Finding
Reduced diameter of a long bone.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Increased vertebral height
MedGen UID:
400628
Concept ID:
C1864853
Finding
Increased top to bottom height of vertebral bodies.
Pectus excavatum
MedGen UID:
781174
Concept ID:
C2051831
Finding
A defect of the chest wall characterized by a depression of the sternum, giving the chest ("pectus") a caved-in ("excavatum") appearance.
Hypoplastic pelvis
MedGen UID:
760700
Concept ID:
C3536734
Anatomical Abnormality
Underdevelopment of the bony pelvis.
Neonatal respiratory distress
MedGen UID:
924182
Concept ID:
C4281993
Finding
Respiratory difficulty as newborn.
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
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.
Thick lower lip vermilion
MedGen UID:
326567
Concept ID:
C1839739
Finding
Increased thickness of the lower lip, leading to a prominent appearance of the lower lip. The height of the vermilion of the lower lip in the midline is more than 2 SD above the mean. Alternatively, an apparently increased height of the vermilion of the lower lip in the frontal view (subjective).
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).
Pointed chin
MedGen UID:
336193
Concept ID:
C1844505
Finding
A marked tapering of the lower face to the chin.
Thick eyebrow
MedGen UID:
377914
Concept ID:
C1853487
Finding
Increased density/number and/or increased diameter of eyebrow hairs.
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.

Term Hierarchy

Professional guidelines

PubMed

Karacan Küçükali G, Keskin M, Aycan Z, Savaş-Erdeve Ş, Çetinkaya S
Eur J Med Genet 2023 Oct;66(10):104828. Epub 2023 Sep 4 doi: 10.1016/j.ejmg.2023.104828. PMID: 37673300
Wit JM, Joustra SD, Losekoot M, van Duyvenvoorde HA, de Bruin C
Horm Res Paediatr 2021;94(3-4):81-104. Epub 2021 Jun 4 doi: 10.1159/000516407. PMID: 34091447

Curated

Holder-Espinasse M, Irving M, Cormier-Daire V
Eur J Hum Genet 2011 Sep;19(9) Epub 2011 Mar 2 doi: 10.1038/ejhg.2011.32. PMID: 21364696Free PMC Article

Recent clinical studies

Etiology

Wang X, He Y, Wang X, Kong X, Lin Y, Yao Y, Huang Y
Mol Genet Genomic Med 2024 Jan;12(1):e2284. Epub 2023 Oct 25 doi: 10.1002/mgg3.2284. PMID: 37877343Free PMC Article
Tüysüz B, Alp Ünkar Z, Turan H, Gezdirici A, Uludağ Alkaya D, Kasap B, Yeşil G, Vural M, Ercan O
Eur J Med Genet 2021 Dec;64(12):104346. Epub 2021 Sep 28 doi: 10.1016/j.ejmg.2021.104346. PMID: 34597859
Shapiro L, Chatterjee S, Ramadan DG, Davies KM, Savage MO, Metherell LA, Storr HL
Eur J Endocrinol 2017 Dec;177(6):485-501. Epub 2017 Sep 4 doi: 10.1530/EJE-17-0453. PMID: 28870985
Abell SK, Shorakae S, Harrison CL, Hiam D, Moreno-Asso A, Stepto NK, De Courten B, Teede HJ
Diabetes Metab Res Rev 2017 Nov;33(8) Epub 2017 Sep 15 doi: 10.1002/dmrr.2926. PMID: 28806491
Boldt K, van Reeuwijk J, Lu Q, Koutroumpas K, Nguyen TM, Texier Y, van Beersum SE, Horn N, Willer JR, Mans DA, Dougherty G, Lamers IJ, Coene KL, Arts HH, Betts MJ, Beyer T, Bolat E, Gloeckner CJ, Haidari K, Hetterschijt L, Iaconis D, Jenkins D, Klose F, Knapp B, Latour B, Letteboer SJ, Marcelis CL, Mitic D, Morleo M, Oud MM, Riemersma M, Rix S, Terhal PA, Toedt G, van Dam TJ, de Vrieze E, Wissinger Y, Wu KM, Apic G, Beales PL, Blacque OE, Gibson TJ, Huynen MA, Katsanis N, Kremer H, Omran H, van Wijk E, Wolfrum U, Kepes F, Davis EE, Franco B, Giles RH, Ueffing M, Russell RB, Roepman R; UK10K Rare Diseases Group
Nat Commun 2016 May 13;7:11491. doi: 10.1038/ncomms11491. PMID: 27173435Free PMC Article

Diagnosis

Wang X, He Y, Wang X, Kong X, Lin Y, Yao Y, Huang Y
Mol Genet Genomic Med 2024 Jan;12(1):e2284. Epub 2023 Oct 25 doi: 10.1002/mgg3.2284. PMID: 37877343Free PMC Article
Karacan Küçükali G, Keskin M, Aycan Z, Savaş-Erdeve Ş, Çetinkaya S
Eur J Med Genet 2023 Oct;66(10):104828. Epub 2023 Sep 4 doi: 10.1016/j.ejmg.2023.104828. PMID: 37673300
Tüysüz B, Alp Ünkar Z, Turan H, Gezdirici A, Uludağ Alkaya D, Kasap B, Yeşil G, Vural M, Ercan O
Eur J Med Genet 2021 Dec;64(12):104346. Epub 2021 Sep 28 doi: 10.1016/j.ejmg.2021.104346. PMID: 34597859
Wit JM, Joustra SD, Losekoot M, van Duyvenvoorde HA, de Bruin C
Horm Res Paediatr 2021;94(3-4):81-104. Epub 2021 Jun 4 doi: 10.1159/000516407. PMID: 34091447
Clayton PE, Hanson D, Magee L, Murray PG, Saunders E, Abu-Amero SN, Moore GE, Black GC
Clin Endocrinol (Oxf) 2012 Sep;77(3):335-42. doi: 10.1111/j.1365-2265.2012.04428.x. PMID: 22624670

Therapy

Karacan Küçükali G, Keskin M, Aycan Z, Savaş-Erdeve Ş, Çetinkaya S
Eur J Med Genet 2023 Oct;66(10):104828. Epub 2023 Sep 4 doi: 10.1016/j.ejmg.2023.104828. PMID: 37673300
Yang M, Patni N
J Pediatr Endocrinol Metab 2020 Dec 16;33(12):1609-1612. Epub 2020 Aug 17 doi: 10.1515/jpem-2020-0278. PMID: 32924381
Abell SK, Shorakae S, Harrison CL, Hiam D, Moreno-Asso A, Stepto NK, De Courten B, Teede HJ
Diabetes Metab Res Rev 2017 Nov;33(8) Epub 2017 Sep 15 doi: 10.1002/dmrr.2926. PMID: 28806491
Keskin M, Muratoğlu Şahin N, Kurnaz E, Bayramoğlu E, Savaş Erdeve Ş, Aycan Z, Çetinkaya S
J Clin Res Pediatr Endocrinol 2017 Mar 1;9(1):91-94. Epub 2016 Oct 31 doi: 10.4274/jcrpe.3238. PMID: 27796265Free PMC Article
Clayton PE, Hanson D, Magee L, Murray PG, Saunders E, Abu-Amero SN, Moore GE, Black GC
Clin Endocrinol (Oxf) 2012 Sep;77(3):335-42. doi: 10.1111/j.1365-2265.2012.04428.x. PMID: 22624670

Prognosis

Yang M, Patni N
J Pediatr Endocrinol Metab 2020 Dec 16;33(12):1609-1612. Epub 2020 Aug 17 doi: 10.1515/jpem-2020-0278. PMID: 32924381
Shapiro L, Chatterjee S, Ramadan DG, Davies KM, Savage MO, Metherell LA, Storr HL
Eur J Endocrinol 2017 Dec;177(6):485-501. Epub 2017 Sep 4 doi: 10.1530/EJE-17-0453. PMID: 28870985
Abell SK, Shorakae S, Harrison CL, Hiam D, Moreno-Asso A, Stepto NK, De Courten B, Teede HJ
Diabetes Metab Res Rev 2017 Nov;33(8) Epub 2017 Sep 15 doi: 10.1002/dmrr.2926. PMID: 28806491
Boldt K, van Reeuwijk J, Lu Q, Koutroumpas K, Nguyen TM, Texier Y, van Beersum SE, Horn N, Willer JR, Mans DA, Dougherty G, Lamers IJ, Coene KL, Arts HH, Betts MJ, Beyer T, Bolat E, Gloeckner CJ, Haidari K, Hetterschijt L, Iaconis D, Jenkins D, Klose F, Knapp B, Latour B, Letteboer SJ, Marcelis CL, Mitic D, Morleo M, Oud MM, Riemersma M, Rix S, Terhal PA, Toedt G, van Dam TJ, de Vrieze E, Wissinger Y, Wu KM, Apic G, Beales PL, Blacque OE, Gibson TJ, Huynen MA, Katsanis N, Kremer H, Omran H, van Wijk E, Wolfrum U, Kepes F, Davis EE, Franco B, Giles RH, Ueffing M, Russell RB, Roepman R; UK10K Rare Diseases Group
Nat Commun 2016 May 13;7:11491. doi: 10.1038/ncomms11491. PMID: 27173435Free PMC Article

Clinical prediction guides

Karacan Küçükali G, Keskin M, Aycan Z, Savaş-Erdeve Ş, Çetinkaya S
Eur J Med Genet 2023 Oct;66(10):104828. Epub 2023 Sep 4 doi: 10.1016/j.ejmg.2023.104828. PMID: 37673300
Tüysüz B, Alp Ünkar Z, Turan H, Gezdirici A, Uludağ Alkaya D, Kasap B, Yeşil G, Vural M, Ercan O
Eur J Med Genet 2021 Dec;64(12):104346. Epub 2021 Sep 28 doi: 10.1016/j.ejmg.2021.104346. PMID: 34597859
Woolley SA, Hayes SE, Shariflou MR, Nicholas FW, Willet CE, O'Rourke BA, Tammen I
BMC Genet 2020 Sep 15;21(1):106. doi: 10.1186/s12863-020-00913-8. PMID: 32933480Free PMC Article
Abell SK, Shorakae S, Harrison CL, Hiam D, Moreno-Asso A, Stepto NK, De Courten B, Teede HJ
Diabetes Metab Res Rev 2017 Nov;33(8) Epub 2017 Sep 15 doi: 10.1002/dmrr.2926. PMID: 28806491
Boldt K, van Reeuwijk J, Lu Q, Koutroumpas K, Nguyen TM, Texier Y, van Beersum SE, Horn N, Willer JR, Mans DA, Dougherty G, Lamers IJ, Coene KL, Arts HH, Betts MJ, Beyer T, Bolat E, Gloeckner CJ, Haidari K, Hetterschijt L, Iaconis D, Jenkins D, Klose F, Knapp B, Latour B, Letteboer SJ, Marcelis CL, Mitic D, Morleo M, Oud MM, Riemersma M, Rix S, Terhal PA, Toedt G, van Dam TJ, de Vrieze E, Wissinger Y, Wu KM, Apic G, Beales PL, Blacque OE, Gibson TJ, Huynen MA, Katsanis N, Kremer H, Omran H, van Wijk E, Wolfrum U, Kepes F, Davis EE, Franco B, Giles RH, Ueffing M, Russell RB, Roepman R; UK10K Rare Diseases Group
Nat Commun 2016 May 13;7:11491. doi: 10.1038/ncomms11491. PMID: 27173435Free PMC Article

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