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3M syndrome 3(3M3)

MedGen UID:
481776
Concept ID:
C3280146
Disease or Syndrome
Synonyms: 3-M Syndrome, CCDC8-Related; Three M syndrome 3
 
Gene (location): CCDC8 (19q13.32)
 
Monarch Initiative: MONDO:0013627
OMIM®: 614205

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

Additional description

From OMIM
3M syndrome is characterized by poor postnatal growth and distinctive facial features, including triangular facies, frontal bossing, fleshy tipped nose, and fleshy lips. Other features may include skeletal anomalies and prominent heels (summary by Hanson et al., 2011). For a general phenotypic description and a discussion of genetic heterogeneity of 3M syndrome, see 3M1 (273750).  http://www.omim.org/entry/614205

Clinical features

From HPO
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).
Prominent calcaneus
MedGen UID:
866740
Concept ID:
C4021088
Anatomical Abnormality
Protruding heel bone, or calcaneus.
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.
Decreased body weight
MedGen UID:
375512
Concept ID:
C1844806
Finding
Abnormally low body weight.
Protruding ear
MedGen UID:
343309
Concept ID:
C1855285
Finding
Angle formed by the plane of the ear and the mastoid bone greater than the 97th centile for age (objective); or, outer edge of the helix more than 2 cm from the mastoid at the point of maximum distance (objective).
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.
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 ability of a joint to move beyond its normal range of motion.
Increased vertebral height
MedGen UID:
400628
Concept ID:
C1864853
Finding
Increased top to bottom height of vertebral bodies.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Hip dysplasia
MedGen UID:
1640560
Concept ID:
C4551649
Congenital Abnormality
The presence of developmental dysplasia of the hip.
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.
Thick vermilion border
MedGen UID:
332232
Concept ID:
C1836543
Finding
Increased width of the skin of vermilion border region of upper lip.
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.
Midface retrusion
MedGen UID:
339938
Concept ID:
C1853242
Anatomical Abnormality
Posterior positions and/or vertical shortening of the infraorbital and perialar regions, or increased concavity of the face and/or reduced nasolabial angle.
Prominent nasal tip
MedGen UID:
383839
Concept ID:
C1856118
Finding
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

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
Simsek-Kiper PO, Taskiran E, Kosukcu C, Arslan UE, Cormier-Daire V, Gonc N, Ozon A, Alikasifoglu A, Kandemir N, Utine GE, Alanay Y, Alikasifoglu M, Boduroglu K
Am J Med Genet A 2019 Jul;179(7):1157-1172. Epub 2019 Apr 13 doi: 10.1002/ajmg.a.61154. PMID: 30980518
Holder-Espinasse M, Irving M, Cormier-Daire V
Eur J Hum Genet 2014 Apr;22(4) Epub 2013 Jul 31 doi: 10.1038/ejhg.2013.156. PMID: 23900270Free PMC Article

Recent clinical studies

Etiology

Khachnaoui-Zaafrane K, Ouertani I, Zanati A, Kandara H, Maazoul F, Mrad R
Eur J Med Genet 2022 Mar;65(3):104448. Epub 2022 Feb 9 doi: 10.1016/j.ejmg.2022.104448. PMID: 35150935
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
Andrews A, Maharaj A, Cottrell E, Chatterjee S, Shah P, Denvir L, Dumic K, Bossowski A, Mushtaq T, Vukovic R, Didi M, Shaw N, Metherell LA, Savage MO, Storr HL
J Clin Endocrinol Metab 2021 Oct 21;106(11):e4716-e4733. doi: 10.1210/clinem/dgab437. PMID: 34136918Free PMC Article
Simsek-Kiper PO, Taskiran E, Kosukcu C, Arslan UE, Cormier-Daire V, Gonc N, Ozon A, Alikasifoglu A, Kandemir N, Utine GE, Alanay Y, Alikasifoglu M, Boduroglu K
Am J Med Genet A 2019 Jul;179(7):1157-1172. Epub 2019 Apr 13 doi: 10.1002/ajmg.a.61154. PMID: 30980518
Meazza C, Lausch E, Pagani S, Bozzola E, Calcaterra V, Superti-Furga A, Silengo M, Bozzola M
Ital J Pediatr 2013 Mar 21;39:21. doi: 10.1186/1824-7288-39-21. PMID: 23517720Free PMC Article

Diagnosis

Andrews A, Maharaj A, Cottrell E, Chatterjee S, Shah P, Denvir L, Dumic K, Bossowski A, Mushtaq T, Vukovic R, Didi M, Shaw N, Metherell LA, Savage MO, Storr HL
J Clin Endocrinol Metab 2021 Oct 21;106(11):e4716-e4733. doi: 10.1210/clinem/dgab437. PMID: 34136918Free PMC Article
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
Simsek-Kiper PO, Taskiran E, Kosukcu C, Arslan UE, Cormier-Daire V, Gonc N, Ozon A, Alikasifoglu A, Kandemir N, Utine GE, Alanay Y, Alikasifoglu M, Boduroglu K
Am J Med Genet A 2019 Jul;179(7):1157-1172. Epub 2019 Apr 13 doi: 10.1002/ajmg.a.61154. PMID: 30980518
Hu X, Li H, Gui B, Xu Y, Wang J, Li N, Su J, Zhang S, Song Y, Wang Y, Luo J, Fan X, Wang J, Chen S, Gong C, Shen Y
Clin Chim Acta 2017 Nov;474:159-164. Epub 2017 Sep 29 doi: 10.1016/j.cca.2017.09.022. PMID: 28969986
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

Lee IK, Lim HH, Kim YM
Yonsei Med J 2020 Nov;61(11):981-985. doi: 10.3349/ymj.2020.61.11.981. PMID: 33107243Free PMC Article
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
Meazza C, Lausch E, Pagani S, Bozzola E, Calcaterra V, Superti-Furga A, Silengo M, Bozzola M
Ital J Pediatr 2013 Mar 21;39:21. doi: 10.1186/1824-7288-39-21. PMID: 23517720Free 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

Andrews A, Maharaj A, Cottrell E, Chatterjee S, Shah P, Denvir L, Dumic K, Bossowski A, Mushtaq T, Vukovic R, Didi M, Shaw N, Metherell LA, Savage MO, Storr HL
J Clin Endocrinol Metab 2021 Oct 21;106(11):e4716-e4733. doi: 10.1210/clinem/dgab437. PMID: 34136918Free PMC Article
Lee IK, Lim HH, Kim YM
Yonsei Med J 2020 Nov;61(11):981-985. doi: 10.3349/ymj.2020.61.11.981. PMID: 33107243Free PMC Article
Hu L, Wang X, Jin T, Han Y, Liu J, Jiang M, Yan S, Fu X, An B, Huang S
J Clin Lab Anal 2020 Jul;34(7):e23265. Epub 2020 Mar 6 doi: 10.1002/jcla.23265. PMID: 32141654Free 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
Meazza C, Lausch E, Pagani S, Bozzola E, Calcaterra V, Superti-Furga A, Silengo M, Bozzola M
Ital J Pediatr 2013 Mar 21;39:21. doi: 10.1186/1824-7288-39-21. PMID: 23517720Free PMC Article

Clinical prediction guides

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
Lee IK, Lim HH, Kim YM
Yonsei Med J 2020 Nov;61(11):981-985. doi: 10.3349/ymj.2020.61.11.981. PMID: 33107243Free PMC Article
Simsek-Kiper PO, Taskiran E, Kosukcu C, Arslan UE, Cormier-Daire V, Gonc N, Ozon A, Alikasifoglu A, Kandemir N, Utine GE, Alanay Y, Alikasifoglu M, Boduroglu K
Am J Med Genet A 2019 Jul;179(7):1157-1172. Epub 2019 Apr 13 doi: 10.1002/ajmg.a.61154. PMID: 30980518
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
Meazza C, Lausch E, Pagani S, Bozzola E, Calcaterra V, Superti-Furga A, Silengo M, Bozzola M
Ital J Pediatr 2013 Mar 21;39:21. doi: 10.1186/1824-7288-39-21. PMID: 23517720Free PMC Article

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