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3MC syndrome 2(3MC2)

MedGen UID:
167115
Concept ID:
C0796279
Disease or Syndrome
Synonyms: Carnevale Krajewska Fischetto syndrome; Carnevale syndrome; Oculo-skeletal-abdominal syndrome; OSA syndrome; Ptosis of eyelids with diastasis recti and hip dysplasia
 
Gene (location): COLEC11 (2p25.3)
 
Monarch Initiative: MONDO:0009927
OMIM®: 265050
Orphanet: ORPHA2998

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.
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.
Limited elbow movement
MedGen UID:
337930
Concept ID:
C1849955
Finding
Postnatal growth retardation
MedGen UID:
395343
Concept ID:
C1859778
Finding
Slow or limited growth after birth.
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Torticollis
MedGen UID:
11859
Concept ID:
C0040485
Sign or Symptom
Torticollis is a twisted neck as a result of shortening of sternocleidomastoid muscle. This short and fibrotic muscle pulls the head laterally and rotates the chin and face to the opposite end. Facial asymmetry may be a manifestation (summary by Engin et al., 1997).
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.
Craniosynostosis syndrome
MedGen UID:
1163
Concept ID:
C0010278
Disease or Syndrome
Craniosynostosis refers to the premature closure of the cranial sutures. Primary craniosynostosis refers to the closure of one or more sutures due to abnormalities in skull development, and secondary craniosynostosis results from failure of brain growth.
Hip dislocation
MedGen UID:
42455
Concept ID:
C0019554
Injury or Poisoning
Displacement of the femur from its normal location in the hip joint.
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).
Hypoplasia of the musculature
MedGen UID:
66010
Concept ID:
C0240414
Finding
Underdevelopment of the musculature.
Skull asymmetry
MedGen UID:
140861
Concept ID:
C0424690
Finding
Abnormal vertebral morphology
MedGen UID:
371742
Concept ID:
C1834129
Anatomical Abnormality
An abnormality of one or more of the vertebrae.
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.
Prominence of the premaxilla
MedGen UID:
412683
Concept ID:
C2749369
Finding
Prominent positioning of the premaxilla in relation to the rest of the maxilla, the facial skeleton, or mandible. Not necessarily caused by an increase in size (hypertrophy of) the premaxilla.
Caudal appendage
MedGen UID:
478747
Concept ID:
C3277117
Finding
The presence of a tail-like skin appendage located adjacent to the sacrum.
Abnormality of the vertebral column
MedGen UID:
892426
Concept ID:
C4021789
Anatomical Abnormality
Any abnormality of the vertebral column.
Partial abdominal muscle agenesis
MedGen UID:
870771
Concept ID:
C4025228
Finding
Failure to form of portions of the abdominal musculature.
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.
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).
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
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.
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.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Broad philtrum
MedGen UID:
344210
Concept ID:
C1854111
Finding
Distance between the philtral ridges, measured just above the vermilion border, more than 2 standard deviations above the mean, or alternatively, an apparently increased distance between the ridges of the philtrum.
Prominent nasal bridge
MedGen UID:
343051
Concept ID:
C1854113
Finding
Anterior positioning of the nasal root in comparison to the usual positioning for age.
Depressed nasal tip
MedGen UID:
347214
Concept ID:
C1859717
Finding
Decreased distance from the nasal tip to the nasal base.
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.
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).
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.

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, 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

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

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

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
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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