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3MC syndrome 3(3MC3)

MedGen UID:
208657
Concept ID:
C0796032
Disease or Syndrome
Synonyms: Facial clefting syndrome Gypsy type; Malpuech facial clefting syndrome; Malpuech syndrome
 
Gene (location): COLEC10 (8q24.12)
 
Monarch Initiative: MONDO:0009554
OMIM®: 248340
Orphanet: ORPHA2453

Definition

The term '3MC syndrome' encompasses 4 rare autosomal recessive disorders that were previously designated the Carnevale, Mingarelli, Malpuech, and Michels syndromes, respectively. The main features of these syndromes are facial dysmorphism that includes hypertelorism, blepharophimosis, blepharoptosis, and highly arched eyebrows, which are present in 70 to 95% of cases. Cleft lip and palate, postnatal growth deficiency, cognitive impairment, and hearing loss are also consistent findings, occurring in 40 to 68% of cases. Craniosynostosis, radioulnar synostosis, and genital and vesicorenal anomalies occur in 20 to 30% of cases. Rare features include anterior chamber defects, cardiac anomalies, caudal appendage, umbilical hernia (omphalocele), and diastasis recti (summary by Rooryck et al., 2011). For a discussion of genetic heterogeneity of 3MC syndrome, see 3MC1 (257920). [from OMIM]

Additional description

From MedlinePlus Genetics
3MC syndrome is a disorder characterized by unusual facial features and problems affecting other tissues and organs.

3MC syndrome encompasses four disorders that were formerly considered to be separate: Mingarelli, Malpeuch, Michels, and Carnevale syndromes. Researchers now generally consider these disorders to be part of the same condition, which is called 3MC based on the initials of the older condition names.

The distinctive facial features of people with 3MC syndrome include widely spaced eyes (hypertelorism), a narrowing of the eye opening (blepharophimosis), droopy eyelids (ptosis), highly arched eyebrows, and an opening in the upper lip (cleft lip) with an opening in the roof of the mouth (cleft palate).

Other common features of 3MC syndrome include developmental delay, intellectual disability, hearing loss, and slow growth after birth resulting in short stature. Less often, individuals with 3MC syndrome can have abnormal fusion of certain bones in the skull (craniosynostosis) or forearm (radioulnar synostosis); an outgrowth of the tailbone (caudal appendage); a soft out-pouching around the belly-button (an umbilical hernia); and abnormalities of the kidneys, bladder, or genitals.  https://medlineplus.gov/genetics/condition/3mc-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).
Horseshoe kidney
MedGen UID:
65140
Concept ID:
C0221353
Congenital Abnormality
A connection of the right and left kidney by an isthmus of functioning renal parenchyma or fibrous tissue that crosses the midline.
Bifid scrotum
MedGen UID:
90968
Concept ID:
C0341787
Congenital Abnormality
Midline indentation or cleft of the scrotum.
Penoscrotal hypospadias
MedGen UID:
105291
Concept ID:
C0452147
Congenital Abnormality
A severe form of hypospadias in which the urethral opening is located at the junction of the penis and scrotum.
Micropenis
MedGen UID:
1633603
Concept ID:
C4551492
Congenital Abnormality
Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.
Preaxial polydactyly
MedGen UID:
87498
Concept ID:
C0345354
Congenital Abnormality
A form of polydactyly in which the extra digit or digits are localized on the side of the thumb or great toe.
Clinodactyly
MedGen UID:
1644094
Concept ID:
C4551485
Congenital Abnormality
An angulation of a digit at an interphalangeal joint in the plane of the palm (finger) or sole (toe).
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.
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.
Abnormal pinna morphology
MedGen UID:
167800
Concept ID:
C0857379
Congenital Abnormality
An abnormality of the pinna, which is also referred to as the auricle or external ear.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Auricular pit
MedGen UID:
868280
Concept ID:
C4022672
Finding
Small indentation in the lower part of the ascending helix, concha, or in the crus helix.
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.
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.
Radioulnar synostosis
MedGen UID:
57861
Concept ID:
C0158761
Congenital Abnormality
An abnormal osseous union (fusion) between the radius and the ulna.
Diastasis recti
MedGen UID:
113171
Concept ID:
C0221766
Disease or Syndrome
A separation of the rectus abdominis muscle into right and left halves (which are normally joined at the midline at the linea alba).
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.
Cleft upper lip
MedGen UID:
40327
Concept ID:
C0008924
Congenital Abnormality
A gap or groove in the upper lip. This is a congenital defect resulting from nonfusion of tissues of the lip during embryonal development.
Tessier cleft
MedGen UID:
146898
Concept ID:
C0685787
Congenital Abnormality
A congenital malformation with a cleft (gap or opening) in the face.
Epicanthus inversus
MedGen UID:
224913
Concept ID:
C1303003
Finding
A fold of skin starting at or just below the medial aspect of the lower lid and arching upward to cover, extend in front of and lateral to the medial canthus.
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.
Cleft palate
MedGen UID:
756015
Concept ID:
C2981150
Congenital Abnormality
Cleft palate is a developmental defect of the palate resulting from a failure of fusion of the palatine processes and manifesting as a separation of the roof of the mouth (soft and hard palate).
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.
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).
Corneal opacity
MedGen UID:
40485
Concept ID:
C0010038
Finding
A reduction of corneal clarity.
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).

Professional guidelines

Recent clinical studies

Etiology

Fatti G, Ngorima-Mabhena N, Tiam A, Tukei BB, Kasu T, Muzenda T, Maile K, Lombard C, Chasela C, Grimwood A
J Int AIDS Soc 2021 Oct;24 Suppl 6(Suppl 6):e25819. doi: 10.1002/jia2.25819. PMID: 34713614Free PMC Article
Selman L, Hansen S
Immunobiology 2012 Sep;217(9):851-63. Epub 2012 Feb 4 doi: 10.1016/j.imbio.2011.12.008. PMID: 22475410
Selman L, Henriksen ML, Brandt J, Palarasah Y, Waters A, Beales PL, Holmskov U, Jørgensen TJ, Nielsen C, Skjodt K, Hansen S
J Immunol Methods 2012 Jan 31;375(1-2):182-8. Epub 2011 Oct 20 doi: 10.1016/j.jim.2011.10.010. PMID: 22301270Free PMC Article

Diagnosis

Ashton CJ, Perveen R, Beaman G, Crisponi G, González-Del Angel A, Garza-Mayén G, Alcántara-Ortigoza MA, O'Sullivan J, Clayton-Smith J
Clin Dysmorphol 2023 Jan 1;32(1):7-13. Epub 2022 Nov 28 doi: 10.1097/MCD.0000000000000443. PMID: 36503917
Graul-Neumann LM, Mensah MA, Klopocki E, Uebe S, Ekici AB, Thiel CT, Reis A, Zweier C
Eur J Med Genet 2018 Jul;61(7):363-368. Epub 2018 Jan 31 doi: 10.1016/j.ejmg.2018.01.016. PMID: 29407414
Selman L, Henriksen ML, Brandt J, Palarasah Y, Waters A, Beales PL, Holmskov U, Jørgensen TJ, Nielsen C, Skjodt K, Hansen S
J Immunol Methods 2012 Jan 31;375(1-2):182-8. Epub 2011 Oct 20 doi: 10.1016/j.jim.2011.10.010. PMID: 22301270Free PMC Article
Titomanlio L, Bennaceur S, Bremond-Gignac D, Baumann C, Dupuy O, Verloes A
Am J Med Genet A 2005 Sep 1;137A(3):332-5. doi: 10.1002/ajmg.a.30878. PMID: 16096999

Therapy

Fatti G, Ngorima-Mabhena N, Tiam A, Tukei BB, Kasu T, Muzenda T, Maile K, Lombard C, Chasela C, Grimwood A
J Int AIDS Soc 2021 Oct;24 Suppl 6(Suppl 6):e25819. doi: 10.1002/jia2.25819. PMID: 34713614Free PMC Article

Clinical prediction guides

Hansen SW, Ohtani K, Roy N, Wakamiya N
Immunobiology 2016 Oct;221(10):1058-67. Epub 2016 Jun 2 doi: 10.1016/j.imbio.2016.05.012. PMID: 27377710
Venkatraman Girija U, Furze CM, Gingras AR, Yoshizaki T, Ohtani K, Marshall JE, Wallis AK, Schwaeble WJ, El-Mezgueldi M, Mitchell DA, Moody PC, Wakamiya N, Wallis R
BMC Biol 2015 Apr 17;13:27. doi: 10.1186/s12915-015-0136-2. PMID: 25912189Free PMC Article
Selman L, Hansen S
Immunobiology 2012 Sep;217(9):851-63. Epub 2012 Feb 4 doi: 10.1016/j.imbio.2011.12.008. PMID: 22475410
Ohata H, Tetsuka T, Hayashi H, Onozaki K, Okamoto T
Microbiol Immunol 2003;47(5):363-70. doi: 10.1111/j.1348-0421.2003.tb03408.x. PMID: 12825898

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