CFSMR
MCID: CRN212
MIFTS: 43

Craniofacial Dysmorphism, Skeletal Anomalies, and Mental Retardation Syndrome (CFSMR)

Categories: Bone diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Craniofacial Dysmorphism, Skeletal Anomalies, and Mental...

MalaCards integrated aliases for Craniofacial Dysmorphism, Skeletal Anomalies, and Mental Retardation Syndrome:

Name: Craniofacial Dysmorphism, Skeletal Anomalies, and Mental Retardation Syndrome 56 25 36 29 6
Cerebrofaciothoracic Dysplasia 56 52 25 58 73 39 71
Cfsmr 56 25 73
Cerebro Facio Thoracic Dysplasia 52 29
Cerebro-Facio-Thoracic Dysplasia 25 73
Pascual-Castroviejo Syndrome 52 25
Tmco1 Defect Syndrome 25 73
Dysmorphism, Craniofacial, Skeletal Anomalies, and Mental Retardation Syndrome 39
Craniofacial Dysmorphism, Skeletal Anomalies and Mental Retardation Syndrome 73
Pascual-Castroviejo Syndrome Type 1 58
Musculoskeletal Abnormalities 43
Pascual Castroviejo Syndrome 71
Cftd 25

Characteristics:

Orphanet epidemiological data:

58
cerebrofaciothoracic dysplasia
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
variable phenotype
patients from old order amish community and turkey have been reported
onset prenatally or at birth


HPO:

31
craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare bone diseases
Developmental anomalies during embryogenesis


Summaries for Craniofacial Dysmorphism, Skeletal Anomalies, and Mental...

Genetics Home Reference : 25 Cerebro-facio-thoracic dysplasia is a rare condition characterized by abnormal development (dysplasia) of the brain (cerebro) and structures in the face (facio) and torso (thoracic). The problems with development lead to the key features of cerebro-facio-thoracic dysplasia, which include severe intellectual disability, distinctive facial features, and abnormalities of the ribs and spinal bones (vertebrae). In addition to intellectual disability, individuals with cerebro-facio-thoracic dysplasia have delayed development of speech and movement (motor) skills, and in some, these skills never develop. Nearly one-quarter of affected individuals never learn to speak and almost half are unable to walk. Weak muscle tone (hypotonia) and difficulty feeding occur in some affected infants. People with cerebro-facio-thoracic dysplasia can have behavioral problems, such as anxiety, autism spectrum disorder, or self-injuring behavior; however, many people with the condition are described as friendly and good-natured. Distinctive facial features common in cerebro-facio-thoracic dysplasia include a wide, short skull (brachycephaly); highly arched eyebrows or eyebrows that grow together in the middle (synophrys); widely spaced eyes (hypertelorism); a wide nasal bridge; low-set ears; an upper lip with pronounced curves (Cupid's bow upper lip); and small teeth (microdontia). Some affected individuals have overgrowth of the gums (gingival hyperplasia), an opening in the roof of the mouth (cleft palate), or a split in the upper lip (cleft lip). Problems with bone development in the torso (thorax) commonly leads to bone abnormalities such as two or more ribs that are joined together (fused) or ribs that are abnormally shaped with two prongs at one end (bifid ribs). Many people with cerebro-facio-thoracic dysplasia have abnormal side-to-side curvature of the spine (scoliosis) due to malformation of the vertebrae; some vertebrae may also be fused. Additionally, the shoulder blades can be affected in people with this condition. A wide variety of other features can occur in cerebro-facio-thoracic dysplasia, such as abnormalities involving the eyes, skin, or hair. Heart defects, digestive problems, or genitourinary problems (such as abnormal kidneys or reproductive organs) can also occur. Affected individuals may also have bone or joint abnormalities in other parts of the body.

MalaCards based summary : Craniofacial Dysmorphism, Skeletal Anomalies, and Mental Retardation Syndrome, also known as cerebrofaciothoracic dysplasia, is related to congenital fiber-type disproportion and zttk syndrome. An important gene associated with Craniofacial Dysmorphism, Skeletal Anomalies, and Mental Retardation Syndrome is TMCO1 (Transmembrane And Coiled-Coil Domains 1). The drugs Levodopa and Dopamine have been mentioned in the context of this disorder. Affiliated tissues include bone, eye and kidney, and related phenotypes are intellectual disability and hypertelorism

KEGG : 36 Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome (CFSMR) is an autosomal recessive disease caused by TMCO1 deficiency. The function of TMCO1 is unknown, however, a critical role for TMCO1 in early fetal growth and development has been suggested.

UniProtKB/Swiss-Prot : 73 Craniofacial dysmorphism, skeletal anomalies and mental retardation syndrome: A disorder characterized by craniofacial and skeletal anomalies, associated with mental retardation. Typical craniofacial dysmorphism include brachycephaly, highly arched bushy eyebrows, synophrys, long eyelashes, low-set ears, microdontism of primary teeth, and generalized gingival hyperplasia, whereas Sprengel deformity of scapula, fusion of spine, rib abnormities, pectus excavatum, and pes planus represent skeletal anomalies.

More information from OMIM: 213980

Related Diseases for Craniofacial Dysmorphism, Skeletal Anomalies, and Mental...

Diseases related to Craniofacial Dysmorphism, Skeletal Anomalies, and Mental Retardation Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 86)
# Related Disease Score Top Affiliating Genes
1 congenital fiber-type disproportion 12.3
2 zttk syndrome 12.0
3 phace association 11.8
4 minicore myopathy with external ophthalmoplegia 11.2
5 spinocerebellar ataxia, autosomal recessive 8 11.2
6 imagawa-matsumoto syndrome 11.2
7 arthrogryposis, distal, type 7 11.0
8 costello syndrome 11.0
9 wrinkly skin syndrome 11.0
10 mental retardation, x-linked, syndromic, bain type 11.0
11 lowe oculocerebrorenal syndrome 11.0
12 neurodevelopmental disorder with ataxic gait, absent speech, and decreased cortical white matter 11.0
13 waardenburg's syndrome 11.0
14 49, xxxxx 11.0
15 hemangioma 10.7
16 posterior fossa malformation 10.6
17 sturge-weber syndrome 10.4
18 dandy-walker syndrome 10.4
19 cerebellar hypoplasia 10.4
20 hydrocephalus 10.4
21 visual epilepsy 10.4
22 hemangioma of liver 10.4
23 weber syndrome 10.4
24 seizure disorder 10.4
25 myopathy 10.4
26 cleft palate, isolated 10.3
27 hypertelorism 10.3
28 alacrima, achalasia, and mental retardation syndrome 10.3
29 atrial standstill 1 10.2
30 dilated cardiomyopathy 10.2
31 autosomal recessive disease 10.2
32 ptosis 10.2
33 clubfoot 10.2
34 hypothyroidism 10.2
35 myopathy, congenital, with fiber-type disproportion 10.2
36 scoliosis 10.2
37 microcephaly 10.2
38 cleft lip 10.2
39 juvenile rheumatoid arthritis 9.9
40 carpal tunnel syndrome 9.8
41 down syndrome 9.8
42 juvenile arthritis 9.8
43 muscular dystrophy 9.8
44 headache 9.8
45 fibrosis of extraocular muscles, congenital, 1 9.7
46 diaphragmatic hernia, congenital 9.7
47 spondyloepiphyseal dysplasia with congenital joint dislocations 9.7
48 migraine with or without aura 1 9.7
49 pectus excavatum 9.7
50 rheumatoid arthritis 9.7

Graphical network of the top 20 diseases related to Craniofacial Dysmorphism, Skeletal Anomalies, and Mental Retardation Syndrome:



Diseases related to Craniofacial Dysmorphism, Skeletal Anomalies, and Mental Retardation Syndrome

Symptoms & Phenotypes for Craniofacial Dysmorphism, Skeletal Anomalies, and Mental...

Human phenotypes related to Craniofacial Dysmorphism, Skeletal Anomalies, and Mental Retardation Syndrome:

58 31 (show top 50) (show all 81)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 hypertelorism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000316
3 short neck 58 31 hallmark (90%) Very frequent (99-80%) HP:0000470
4 thick eyebrow 58 31 hallmark (90%) Very frequent (99-80%) HP:0000574
5 brachycephaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0000248
6 wide mouth 58 31 hallmark (90%) Very frequent (99-80%) HP:0000154
7 low-set, posteriorly rotated ears 58 31 hallmark (90%) Very frequent (99-80%) HP:0000368
8 hemivertebrae 58 31 hallmark (90%) Very frequent (99-80%) HP:0002937
9 rib fusion 58 31 hallmark (90%) Very frequent (99-80%) HP:0000902
10 narrow chest 58 31 hallmark (90%) Very frequent (99-80%) HP:0000774
11 midface retrusion 58 31 hallmark (90%) Very frequent (99-80%) HP:0011800
12 wide nose 58 31 hallmark (90%) Very frequent (99-80%) HP:0000445
13 bifid ribs 58 31 hallmark (90%) Very frequent (99-80%) HP:0000892
14 broad philtrum 58 31 hallmark (90%) Very frequent (99-80%) HP:0000289
15 hypoplasia of the corpus callosum 58 31 hallmark (90%) Very frequent (99-80%) HP:0002079
16 scoliosis 58 31 occasional (7.5%) Frequent (79-30%) HP:0002650
17 macrocephaly 58 31 frequent (33%) Frequent (79-30%) HP:0000256
18 short nose 58 31 frequent (33%) Frequent (79-30%) HP:0003196
19 coarse hair 58 31 frequent (33%) Frequent (79-30%) HP:0002208
20 short stature 58 31 frequent (33%) Frequent (79-30%) HP:0004322
21 hernia 58 31 frequent (33%) Frequent (79-30%) HP:0100790
22 strabismus 58 31 occasional (7.5%) Frequent (79-30%) HP:0000486
23 low posterior hairline 58 31 frequent (33%) Frequent (79-30%) HP:0002162
24 epicanthus 58 31 frequent (33%) Frequent (79-30%) HP:0000286
25 sprengel anomaly 58 31 frequent (33%) Frequent (79-30%) HP:0000912
26 cerebral cortical atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0002120
27 downslanted palpebral fissures 58 31 frequent (33%) Frequent (79-30%) HP:0000494
28 polyhydramnios 58 31 frequent (33%) Frequent (79-30%) HP:0001561
29 ventriculomegaly 58 31 frequent (33%) Frequent (79-30%) HP:0002119
30 synophrys 58 31 frequent (33%) Frequent (79-30%) HP:0000664
31 cerebellar vermis hypoplasia 58 31 frequent (33%) Frequent (79-30%) HP:0001320
32 cleft palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000175
33 cleft upper lip 58 31 occasional (7.5%) Occasional (29-5%) HP:0000204
34 pes planus 31 occasional (7.5%) HP:0001763
35 microcephaly 31 occasional (7.5%) HP:0000252
36 absent speech 31 occasional (7.5%) HP:0001344
37 attention deficit hyperactivity disorder 31 occasional (7.5%) HP:0007018
38 postnatal growth retardation 31 occasional (7.5%) HP:0008897
39 anxiety 31 occasional (7.5%) HP:0000739
40 ptosis 31 occasional (7.5%) HP:0000508
41 talipes equinovarus 31 occasional (7.5%) HP:0001762
42 joint hypermobility 31 occasional (7.5%) HP:0001382
43 patent ductus arteriosus 31 occasional (7.5%) HP:0001643
44 abnormality of the kidney 31 occasional (7.5%) HP:0000077
45 decreased fetal movement 31 occasional (7.5%) HP:0001558
46 craniosynostosis 31 occasional (7.5%) HP:0001363
47 self-mutilation 31 occasional (7.5%) HP:0000742
48 growth hormone deficiency 31 occasional (7.5%) HP:0000824
49 overlapping toe 31 occasional (7.5%) HP:0001845
50 bull's eye maculopathy 31 occasional (7.5%) HP:0011504

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
hypertelorism
synophrys
long eyelashes
high-arched eyebrows
epicanthal folds (in some patients)
more
Head And Neck Head:
macrocephaly
brachycephaly
microcephaly (rare)

Head And Neck Nose:
short nose
wide ala nasi
hypoplastic ala nasi

Head And Neck Face:
flat face
micrognathia
narrow forehead
low hairline
frontal upsweep (in some patients)

Head And Neck Ears:
low-set, posteriorly rotated ears

Head And Neck Teeth:
microdontia of primary teeth
primary dentition delay

Chest Breasts:
widely spaced nipples

Skeletal Spine:
scoliosis (in some patients)
vertebral segmentation defects (in some patients)

Skeletal Skull:
craniosynostosis (rare)

Chest External Features:
narrow chest (in some patients)

Growth Other:
postnatal growth retardation (some patients)

Skeletal Hands:
long hyperextensible fingers (in some patients)

Prenatal Manifestations Movement:
decreased fetal movement (in some patients)

Head And Neck Neck:
short neck
low posterior hairline

Skeletal Feet:
pes planus
talipes equinovarus (in some patients)

Neurologic Central Nervous System:
neonatal hypotonia
motor delay
mental retardation
speech defect
nonverbal (in some patients)
more
Skin Nails Hair Hair:
low posterior hairline
low anterior hairline
synophrys
long eyelashes
high-arched eyebrows
more
Chest Ribs Sternum Clavicles And Scapulae:
bifid ribs
fused ribs
elevated scapulae

Head And Neck Mouth:
high-arched palate
cleft lip (in some patients)
cleft palate (in some patients)
gingival hyperplasia

Abdomen Gastrointestinal:
poor feeding

Cardiovascular Heart:
atrial septal defect (rare)

Cardiovascular Vascular:
patent ductus arteriosus (in some patients)

Growth Weight:
birthweight > 90th percentile (in some patients)

Genitourinary Kidneys:
renal anomalies (in some patients)

Neurologic Behavioral Psychiatric Manifestations:
anxiety (in some patients)
affable demeanor (in some patients)
attention deficit (in some patients)
self mutilation (in some patients)

Prenatal Manifestations Amniotic Fluid:
polyhydramnios (in some patients)

Clinical features from OMIM:

213980

MGI Mouse Phenotypes related to Craniofacial Dysmorphism, Skeletal Anomalies, and Mental Retardation Syndrome:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 craniofacial MP:0005382 8.62 PAX3 TMCO1

Drugs & Therapeutics for Craniofacial Dysmorphism, Skeletal Anomalies, and Mental...

Drugs for Craniofacial Dysmorphism, Skeletal Anomalies, and Mental Retardation Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 7)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Levodopa Approved Phase 4 59-92-7 6047
2
Dopamine Approved Phase 4 51-61-6, 62-31-7 681
3 Antiparkinson Agents Phase 4
4 Carbidopa, levodopa drug combination Phase 4
5 Dihydroxyphenylalanine Phase 4
6 Neurotransmitter Agents Phase 4
7 Dopamine Agents Phase 4

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Dopamine Treatment in Children With Cerebral Palsy With Dystonia- A Double Blind Controlled Study Unknown status NCT01361373 Phase 4 L- DOPA;placebo
2 Cross-Disciplinary Workplace Intervention Strategy for Chronic Musculoskeletal Disorders Unknown status NCT00369135
3 Role of a Written Summary on Risk Recall During Consent Process for Cleft Palate Repair Unknown status NCT02595307
4 The Efficacy of Exercise Program Based on Motor Learning Principles in Correction of Forward Head Posture Completed NCT03006497
5 A Single-Blinded Randomized Multi-Center Trial to Evaluate the Efficacy and Durability of Myofascial Tissue Manipulation in Women With Interstitial Cystitis/Painful Bladder Syndrome Completed NCT00733603
6 Investigating the Effects of Exercises in Addition to Dynamic Compression Brace in Patients With Pectus Carinatum: a Single Blinded Randomized Controlled Trial Completed NCT03559244
7 Using the Peanut Exercise Ball to Reduce Cesarean Section Rates: A Randomized Controlled Trial Recruiting NCT02899260
8 Pediatric Radio Frequency Coil Development on Clinical and Research MR Scanners Active, not recruiting NCT01633866
9 Musculoskeletal Ultrasound of the Ankles in Erysipelas-like Erythema of Familial Mediterranean Fever Not yet recruiting NCT03917277

Search NIH Clinical Center for Craniofacial Dysmorphism, Skeletal Anomalies, and Mental Retardation Syndrome

Cochrane evidence based reviews: musculoskeletal abnormalities

Genetic Tests for Craniofacial Dysmorphism, Skeletal Anomalies, and Mental...

Genetic tests related to Craniofacial Dysmorphism, Skeletal Anomalies, and Mental Retardation Syndrome:

# Genetic test Affiliating Genes
1 Craniofacial Dysmorphism, Skeletal Anomalies, and Mental Retardation Syndrome 29 TMCO1
2 Cerebro Facio Thoracic Dysplasia 29

Anatomical Context for Craniofacial Dysmorphism, Skeletal Anomalies, and Mental...

MalaCards organs/tissues related to Craniofacial Dysmorphism, Skeletal Anomalies, and Mental Retardation Syndrome:

40
Bone, Eye, Kidney, Brain, Heart, Skin

Publications for Craniofacial Dysmorphism, Skeletal Anomalies, and Mental...

Articles related to Craniofacial Dysmorphism, Skeletal Anomalies, and Mental Retardation Syndrome:

(show all 16)
# Title Authors PMID Year
1
Whole-exome sequencing identified a patient with TMCO1 defect syndrome and expands the phenotic spectrum. 6 56
23320496 2013
2
Homozygous frameshift mutation in TMCO1 causes a syndrome with craniofacial dysmorphism, skeletal anomalies, and mental retardation. 56 6
20018682 2010
3
Cerebro-facio-thoracic dysplasia: expanding the phenotype. 6 56
17351359 2007
4
TMCO1 deficiency causes autosomal recessive cerebrofaciothoracic dysplasia. 6 61
24194475 2014
5
Cerebrofaciothoracic dysplasia: a new family. 61 56
1640432 1992
6
Growth hormone deficiency in a case of cerebrofaciothoracic syndrome in one of two affected siblings. 56
15326640 2004
7
Cerebrofaciothoracic syndrome. 56
8669442 1996
8
Cerebro-facio-thoracic dysplasia: report of three cases. 56
1204988 1975
9
Cerebrofaciothoracic dysplasia: Four new patients with a recurrent TMCO1 pathogenic variant. 61
30556256 2019
10
Whole-exome sequencing links TMCO1 defect syndrome with cerebro-facio-thoracic dysplasia. 61
24424126 2014
11
An additional case of cerebrofaciothoracic dysplasia associated with Chiari type I malformation. 61
23598465 2013
12
Cerebrocostomandibular-like syndrome and a mutation in the conserved oligomeric Golgi complex, subunit 1. 61
19008299 2009
13
Sensorineural deafness, distinctive facial features, and abnormal cranial bones: a new variant of Waardenburg syndrome? 54
18553554 2008
14
[Cerebrofaciothoracic dysplasia (Pascual-Castroviejo type I syndrome): presentation of two new patients]. 61
17610171 2007
15
Two years of growth hormone treatment in the first growth hormone deficient patient with cerebrofaciothoracic dysplasia. 61
17128568 2006
16
Ophthalmologic findings in cerebrofaciothoracic dysplasia. 61
15724898 2005

Variations for Craniofacial Dysmorphism, Skeletal Anomalies, and Mental...

ClinVar genetic disease variations for Craniofacial Dysmorphism, Skeletal Anomalies, and Mental Retardation Syndrome:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TMCO1 NM_001256165.1(TMCO1):c.-252_-251GA[1]short repeat Pathogenic 31100 rs397518448 1:165738001-165738002 1:165768764-165768765
2 TMCO1 NM_019026.4(TMCO1):c.412C>T (p.Arg138Ter)SNV Pathogenic 88739 rs201213306 1:165721403-165721403 1:165752166-165752166
3 TMCO1 NM_001256164.1(TMCO1):c.147-9_147-6deldeletion Pathogenic 189248 rs786204789 1:165737487-165737490 1:165768250-165768253
4 TMCO1 NM_019026.4(TMCO1):c.476+3G>CSNV Pathogenic 218899 rs372701032 1:165721336-165721336 1:165752099-165752099
5 TMCO1 NM_001256164.1(TMCO1):c.188_189AG[1] (p.Gln63_Ser64insTer)short repeat Pathogenic 420165 rs752176040 1:165737437-165737438 1:165768200-165768201
6 TMCO1 NM_019026.4(TMCO1):c.616C>T (p.Arg206Ter)SNV Pathogenic 598963 rs765379963 1:165712409-165712409 1:165743172-165743172
7 TMCO1 NM_019026.4(TMCO1):c.340C>T (p.Arg114Ter)SNV Conflicting interpretations of pathogenicity 265628 rs765824628 1:165728783-165728783 1:165759546-165759546
8 TMCO1 NM_001256164.1(TMCO1):c.146+51C>TSNV Uncertain significance 873451 1:165737945-165737945 1:165768708-165768708

Expression for Craniofacial Dysmorphism, Skeletal Anomalies, and Mental...

Search GEO for disease gene expression data for Craniofacial Dysmorphism, Skeletal Anomalies, and Mental Retardation Syndrome.

Pathways for Craniofacial Dysmorphism, Skeletal Anomalies, and Mental...

GO Terms for Craniofacial Dysmorphism, Skeletal Anomalies, and Mental...

Sources for Craniofacial Dysmorphism, Skeletal Anomalies, and Mental...

3 CDC
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32 ICD10
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