CCFDN
MCID: CNG041
MIFTS: 36

Congenital Cataracts, Facial Dysmorphism, and Neuropathy (CCFDN)

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

Aliases & Classifications for Congenital Cataracts, Facial Dysmorphism, and Neuropathy

MalaCards integrated aliases for Congenital Cataracts, Facial Dysmorphism, and Neuropathy:

Name: Congenital Cataracts, Facial Dysmorphism, and Neuropathy 57 25 43 72 36 13 70
Ccfdn 57 25 43 58 72
Congenital Cataracts-Facial Dysmorphism-Neuropathy Syndrome 58 29 6
Cataract, Congenital, with Facial Dysmorphism and Neuropathy 57
Cataracts, Congenital, Facial Dysmorphism, and Neuropathy 39

Characteristics:

Orphanet epidemiological data:

58
congenital cataracts-facial dysmorphism-neuropathy syndrome
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
neuropathy becomes apparent in childhood
prevalent in bulgarian gypsies
distinct disorder from marinesco-sjogren syndrome (mss, )


HPO:

31
congenital cataracts, facial dysmorphism, and neuropathy:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

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


Summaries for Congenital Cataracts, Facial Dysmorphism, and Neuropathy

MedlinePlus Genetics : 43 Congenital cataracts, facial dysmorphism, and neuropathy (CCFDN) is a rare disorder that affects several parts of the body. It is characterized by a clouding of the lens of the eyes at birth (congenital cataracts) and other eye abnormalities, such as small or poorly developed eyes (microphthalmia) and abnormal eye movements (nystagmus). Affected individuals, particularly males, often have distinctive facial features that become more apparent as they reach adulthood. These features include a prominent midface, a large nose, protruding teeth, and a small lower jaw.CCFDN causes progressive damage to the peripheral nerves, which connect the brain and spinal cord to muscles and sensory cells. This nerve damage is known as peripheral neuropathy. Weakness in the legs, followed by the arms, begins in the first few years of life, and as a result children with CCFDN have delayed development of motor skills such as standing and walking. In adolescence, affected individuals develop sensory abnormalities such as numbness and tingling, mainly in the legs. By adulthood they typically have significant difficulties with mobility. Muscle weakness can also lead to skeletal abnormalities such as hand and foot deformities and abnormal curvature of the spine.People with CCFDN may have problems with balance and coordination (ataxia), tremors, and difficulty with movements that involve judging distance or scale (dysmetria). Some have mild intellectual disability. Individuals with CCFDN have short stature, are typically underweight, and have reduced bone density.A complication called rhabdomyolysis occurs in some people with CCFDN, typically following a viral infection or, in rare cases, during or after surgery. Rhabdomyolysis is a breakdown of muscle tissue that results in severe muscle weakness. The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). The presence of myoglobin causes the urine to be red or brown. The muscles may take up to a year to recover, and the episodes may worsen the muscle weakness caused by the neuropathy.

MalaCards based summary : Congenital Cataracts, Facial Dysmorphism, and Neuropathy, also known as ccfdn, is related to marinesco-sjogren syndrome and cataract, and has symptoms including ataxia and abnormal pyramidal signs. An important gene associated with Congenital Cataracts, Facial Dysmorphism, and Neuropathy is CTDP1 (CTD Phosphatase Subunit 1). Affiliated tissues include eye, spinal cord and testes, and related phenotypes are nystagmus and cataract

OMIM® : 57 Congenital cataracts, facial dysmorphism, and neuropathy is an autosomal recessive disorder that is prevalent among Bulgarian Gypsies. Additional features include delayed psychomotor development, skeletal anomalies, and hypogonadism. The predominantly motor neuropathy becomes evident during childhood and progresses to severe disability by the third decade (Tournev et al., 1999). CCFDN is genetically distinct from Marinesco-Sjogren syndrome (MSS; 248800), although the 2 disorders share some overlapping features, including congenital cataracts, delayed psychomotor development, and ataxia (Merlini et al., 2002). (604168) (Updated 20-May-2021)

KEGG : 36 Congenital cataracts, facial dysmorphism, and neuropathy (CCFDN) syndrome is a rare autosomal recessive, complex developmental disorder exclusively manifested in the Roma population. CCFDN is a genetically homogeneous condition in which all patients are homozygous for the same ancestral mutation in the CTDP1 gene. Affected patients display congenital cataracts, microcornea, peripheral neuropathy, mild facial dysmorphism, hypogonadism, and psychomotor delay.

UniProtKB/Swiss-Prot : 72 Congenital cataracts, facial dysmorphism, and neuropathy: An autosomal recessive developmental disorder characterized by a complex clinical phenotype with seemingly unrelated features involving multiple organs and systems. Developmental abnormalities include congenital cataracts and microcorneae, hypomyelination of the peripheral nervous system, impaired physical growth, delayed early motor and intellectual development, facial dysmorphism and hypogonadism. Central nervous system involvement, with cerebral and spinal cord atrophy, may be the result of disrupted development with superimposed degenerative changes. Affected individuals are prone to severe rhabdomyolysis after viral infections and to serious complications related to general anesthesia (such as pulmonary edema and epileptic seizures).

GeneReviews: NBK25565

Related Diseases for Congenital Cataracts, Facial Dysmorphism, and Neuropathy

Graphical network of the top 20 diseases related to Congenital Cataracts, Facial Dysmorphism, and Neuropathy:



Diseases related to Congenital Cataracts, Facial Dysmorphism, and Neuropathy

Symptoms & Phenotypes for Congenital Cataracts, Facial Dysmorphism, and Neuropathy

Human phenotypes related to Congenital Cataracts, Facial Dysmorphism, and Neuropathy:

58 31 (show top 50) (show all 54)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nystagmus 58 31 hallmark (90%) Very frequent (99-80%) HP:0000639
2 cataract 58 31 hallmark (90%) Very frequent (99-80%) HP:0000518
3 global developmental delay 58 31 hallmark (90%) Very frequent (99-80%) HP:0001263
4 abnormality of peripheral nerve conduction 58 31 hallmark (90%) Very frequent (99-80%) HP:0003134
5 short stature 58 31 hallmark (90%) Very frequent (99-80%) HP:0004322
6 intellectual disability, mild 58 31 hallmark (90%) Very frequent (99-80%) HP:0001256
7 intrauterine growth retardation 58 31 hallmark (90%) Very frequent (99-80%) HP:0001511
8 micrognathia 58 31 hallmark (90%) Very frequent (99-80%) HP:0000347
9 paresthesia 58 31 hallmark (90%) Very frequent (99-80%) HP:0003401
10 dysmetria 58 31 hallmark (90%) Very frequent (99-80%) HP:0001310
11 camptodactyly of finger 58 31 hallmark (90%) Very frequent (99-80%) HP:0100490
12 intention tremor 58 31 hallmark (90%) Very frequent (99-80%) HP:0002080
13 motor axonal neuropathy 58 31 hallmark (90%) Very frequent (99-80%) HP:0007002
14 malar prominence 58 31 hallmark (90%) Very frequent (99-80%) HP:0010620
15 hypogonadotropic hypogonadism 31 hallmark (90%) HP:0000044
16 hypoglycemia 58 31 frequent (33%) Frequent (79-30%) HP:0001943
17 strabismus 58 31 frequent (33%) Frequent (79-30%) HP:0000486
18 osteoporosis 58 31 frequent (33%) Frequent (79-30%) HP:0000939
19 cerebral cortical atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0002120
20 microphthalmia 58 31 frequent (33%) Frequent (79-30%) HP:0000568
21 long eyelashes 58 31 frequent (33%) Frequent (79-30%) HP:0000527
22 abnormality of the cervical spine 58 31 frequent (33%) Frequent (79-30%) HP:0003319
23 acute rhabdomyolysis 58 31 frequent (33%) Frequent (79-30%) HP:0008942
24 scoliosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002650
25 abnormal pyramidal sign 58 31 occasional (7.5%) Occasional (29-5%) HP:0007256
26 kyphosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0002808
27 ventriculomegaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0002119
28 microcornea 58 31 occasional (7.5%) Occasional (29-5%) HP:0000482
29 primary amenorrhea 31 occasional (7.5%) HP:0000786
30 decreased testicular size 31 occasional (7.5%) HP:0008734
31 ataxia 58 31 Very frequent (99-80%) HP:0001251
32 intellectual disability 31 HP:0001249
33 chorea 31 HP:0002072
34 abnormality of the dentition 31 HP:0000164
35 abnormal facial shape 31 HP:0001999
36 cognitive impairment 31 HP:0100543
37 genu recurvatum 31 HP:0002816
38 hypogonadotrophic hypogonadism 58 Very frequent (99-80%)
39 motor delay 31 HP:0001270
40 talipes equinovarus 31 HP:0001762
41 kyphoscoliosis 31 HP:0002751
42 split hand 31 HP:0001171
43 sensory neuropathy 58 Very frequent (99-80%)
44 pes cavus 31 HP:0001761
45 decreased motor nerve conduction velocity 31 HP:0003431
46 babinski sign 31 HP:0003487
47 hypergonadotropic hypogonadism 31 HP:0000815
48 cerebral atrophy 31 HP:0002059
49 decreased serum estradiol 31 HP:0008214
50 developmental cataract 31 HP:0000519

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Eyes:
nystagmus
congenital cataracts
microcorneas

Growth Height:
short stature

Endocrine Features:
hypogonadotrophic hypogonadism
decreased serum estradiol
hypergonadotrophic hypogonadism
decreased serum testosterone
low-to-normal serum growth hormone

Skeletal Spine:
kyphoscoliosis

Neurologic Peripheral Nervous System:
decreased motor nerve conduction velocities (ncv)
demyelination
motor neuropathy beginning in lower limbs
upper limb motor neuropathy occurs later
nerve biopsy shows hypomyelination
more
Head And Neck Teeth:
bimaxillary dentoalveolar protrusion (protruding upper and lower front teeth)

Genitourinary Internal Genitalia Female:
primary amenorrhea (in some patients)

Neurologic Central Nervous System:
ataxia
chorea
cerebral atrophy
delayed motor development
mental retardation
more
Skeletal Limbs:
genu recurvatum

Skeletal Feet:
talipes equinovarus
pes cavus

Head And Neck Face:
facial dysmorphism
prominent midface
thickening of perioral tissues
mandibular retrognathism

Skeletal Hands:
claw hand

Genitourinary Internal Genitalia Male:
small testes (in some patients)

Muscle Soft Tissue:
rhabdomyolysis, acute

Clinical features from OMIM®:

604168 (Updated 20-May-2021)

UMLS symptoms related to Congenital Cataracts, Facial Dysmorphism, and Neuropathy:


ataxia; abnormal pyramidal signs

Drugs & Therapeutics for Congenital Cataracts, Facial Dysmorphism, and Neuropathy

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Retrospective Cohort Study Assessing the Natural Course in Congenital Cataract Facial Dysmorphism Neuropathy Syndrome (CCFDN) and Sporadic and Hereditary Inclusion Body Myopathies (IBM) Completed NCT01902940

Search NIH Clinical Center for Congenital Cataracts, Facial Dysmorphism, and Neuropathy

Genetic Tests for Congenital Cataracts, Facial Dysmorphism, and Neuropathy

Genetic tests related to Congenital Cataracts, Facial Dysmorphism, and Neuropathy:

# Genetic test Affiliating Genes
1 Congenital Cataracts-Facial Dysmorphism-Neuropathy Syndrome 29 CTDP1

Anatomical Context for Congenital Cataracts, Facial Dysmorphism, and Neuropathy

MalaCards organs/tissues related to Congenital Cataracts, Facial Dysmorphism, and Neuropathy:

40
Eye, Spinal Cord, Testes, Brain

Publications for Congenital Cataracts, Facial Dysmorphism, and Neuropathy

Articles related to Congenital Cataracts, Facial Dysmorphism, and Neuropathy:

(show all 38)
# Title Authors PMID Year
1
Partial deficiency of the C-terminal-domain phosphatase of RNA polymerase II is associated with congenital cataracts facial dysmorphism neuropathy syndrome. 57 6 25 61
14517542 2003
2
Long-term follow-up in patients with CCFDN syndrome. 25 57 61
25186864 2014
3
Genetic identity of Marinesco-Sjögren/myoglobinuria and CCFDN syndromes. 25 57 61
11805249 2002
4
Peripheral nerve abnormalities in the congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome. 25 57 61
10442556 1999
5
Congenital cataracts facial dysmorphism neuropathy syndrome, a novel complex genetic disease in Balkan Gypsies: clinical and electrophysiological observations. 61 25 57
10360766 1999
6
Mutation history of the roma/gypsies. 6 25
15322984 2004
7
Marinesco Sjögren syndrome with rhabdomyolysis. A new subtype of the disease. 57 25
9638664 1998
8
Linkage to 18qter differentiates two clinically overlapping syndromes: congenital cataracts-facial dysmorphism-neuropathy (CCFDN) syndrome and Marinesco-Sjögren syndrome. 61 57
12414825 2002
9
Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome: a novel developmental disorder in Gypsies maps to 18qter. 61 57
10439962 1999
10
Anaesthesia and orphan disease: A child with Congenital Cataract Facial Dysmorphism neuropathy (CCFDN) syndrome: a case report. 61 25
28141735 2017
11
Cognitive Impairment and Brain Imaging Characteristics of Patients with Congenital Cataracts, Facial Dysmorphism, Neuropathy Syndrome. 61 25
26060356 2015
12
Congenital cataract, facial dysmorphism and demyelinating neuropathy (CCFDN) in 10 Czech Gypsy children--frequent and underestimated cause of disability among Czech Gypsies. 25 61
24690360 2014
13
Progressive cerebral white matter involvement in a patient with Congenital Cataracts Facial Dysmorphisms Neuropathy (CCFDN). 25 61
20350809 2010
14
Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome: a rare cause of parainfectious rhabdomyolysis. 25 61
17195938 2007
15
Ocular features of the congenital cataracts facial dysmorphism neuropathy syndrome. 25 61
15234148 2004
16
Neuromuscular disorders in the Gypsy ethnic group. A short review. 57
12966699 2003
17
GBA2 Mutations Cause a Marinesco-Sjögren-Like Syndrome: Genetic and Biochemical Studies. 25
28052128 2017
18
Loss of function of glucocerebrosidase GBA2 is responsible for motor neuron defects in hereditary spastic paraplegia. 25
23332916 2013
19
Identification of proteins interacting with the RNAPII FCP1 phosphatase: FCP1 forms a complex with arginine methyltransferase PRMT5 and it is a substrate for PRMT5-mediated methylation. 25
15670829 2005
20
125th ENMC International Workshop: Neuromuscular disorders in the Roma (Gypsy) population, 23-25 April 2004, Naarden, The Netherlands. 25
15639123 2005
21
The FCP1 phosphatase interacts with RNA polymerase II and with MEP50 a component of the methylosome complex involved in the assembly of snRNP. 25
12560496 2003
22
An extensive network of coupling among gene expression machines. 25
11932736 2002
23
Transcription-independent RNA polymerase II dephosphorylation by the FCP1 carboxy-terminal domain phosphatase in Xenopus laevis early embryos. 25
11533226 2001
24
A founder mutation in the GK1 gene is responsible for galactokinase deficiency in Roma (Gypsies). 25
10521295 1999
25
An unusual eukaryotic protein phosphatase required for transcription by RNA polymerase II and CTD dephosphorylation in S. cerevisiae. 25
10445027 1999
26
A protein phosphatase functions to recycle RNA polymerase II. 25
10385623 1999
27
An essential component of a C-terminal domain phosphatase that interacts with transcription factor IIF in Saccharomyces cerevisiae. 25
9405607 1997
28
Ctdp1 deficiency leads to early embryonic lethality in mice and defects in cell cycle progression in MEFs. 61
33408128 2021
29
Biallelic INTS1 Mutations Cause a Rare Neurodevelopmental Disorder in Two Chinese Siblings. 61
31428919 2020
30
Congenital Cataracts, Facial Dysmorphism, and Neuropathy Syndrome: Additional Clinical Features. 61
28041656 2017
31
Carrier rates of four single-gene disorders in Croatian Bayash Roma. 61
24180318 2014
32
Congenital cataracts, facial dysmorphism, and neuropathy syndrome. 61
21824574 2011
33
Clinical utility gene card for: HMSN/HNPP HMSN types 1, 2, 3, 6 (CMT1,2,4, DSN, CHN, GAN, CCFDN, HNA); HNPP. 61
20512157 2010
34
Congenital Cataracts, Facial Dysmorphism, and Neuropathy 61
20301787 2010
35
[Screening for hereditary neuromuscular disorders with molecular genetic methods in the Roma population of Hungary]. 61
19070320 2008
36
[Congenital cataracts facial dysmorphism neuropathy syndrome--first Hungarian case report]. 61
17578274 2007
37
Congenital cataracts-facial dysmorphism-neuropathy. 61
16939648 2006
38
Homozygosity mapping of Marinesco-Sjögren syndrome to 5q31. 61
14512967 2003

Variations for Congenital Cataracts, Facial Dysmorphism, and Neuropathy

ClinVar genetic disease variations for Congenital Cataracts, Facial Dysmorphism, and Neuropathy:

6 (show all 11)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CTDP1 NM_004715.4(CTDP1):c.863+389C>T SNV Pathogenic 5301 rs113994102 GRCh37: 18:77470825-77470825
GRCh38: 18:79710825-79710825
2 CTDP1 NM_004715.5(CTDP1):c.2884T>G (p.Ter962Gly) SNV Pathogenic 998252 GRCh37: 18:77513788-77513788
GRCh38: 18:79753788-79753788
3 CTDP1 NM_004715.5(CTDP1):c.2038_2039del (p.Arg680fs) Deletion Pathogenic 1032260 GRCh37: 18:77475498-77475499
GRCh38: 18:79715498-79715499
4 CTDP1 NM_004715.5(CTDP1):c.2564_2567del (p.Glu855fs) Microsatellite Pathogenic 1032261 GRCh37: 18:77489051-77489054
GRCh38: 18:79729051-79729054
5 CTDP1 NM_004715.5(CTDP1):c.2604del (p.Ser869fs) Deletion Pathogenic 1032262 GRCh37: 18:77496378-77496378
GRCh38: 18:79736378-79736378
6 CTDP1 NM_004715.5(CTDP1):c.808C>T (p.Arg270Ter) SNV Pathogenic 1032263 GRCh37: 18:77470381-77470381
GRCh38: 18:79710381-79710381
7 CTDP1 NM_004715.5(CTDP1):c.2649G>A (p.Glu883=) SNV Likely benign 931410 GRCh37: 18:77496423-77496423
GRCh38: 18:79736423-79736423
8 CTDP1 NM_004715.4(CTDP1):c.1461G>A (p.Pro487=) SNV Benign 286855 rs2126082 GRCh37: 18:77474921-77474921
GRCh38: 18:79714921-79714921
9 CTDP1 NM_004715.4(CTDP1):c.2817T>C (p.Asp939=) SNV Benign 128865 rs626169 GRCh37: 18:77513721-77513721
GRCh38: 18:79753721-79753721
10 CTDP1 NM_004715.4(CTDP1):c.978G>A (p.Thr326=) SNV Benign 518282 rs599554 GRCh37: 18:77473086-77473086
GRCh38: 18:79713086-79713086
11 CTDP1 NM_004715.5(CTDP1):c.2418-207_2418-165dup Duplication Benign 803507 rs147933855 GRCh37: 18:77488698-77488699
GRCh38: 18:79728698-79728699

Expression for Congenital Cataracts, Facial Dysmorphism, and Neuropathy

Search GEO for disease gene expression data for Congenital Cataracts, Facial Dysmorphism, and Neuropathy.

Pathways for Congenital Cataracts, Facial Dysmorphism, and Neuropathy

GO Terms for Congenital Cataracts, Facial Dysmorphism, and Neuropathy

Sources for Congenital Cataracts, Facial Dysmorphism, and Neuropathy

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
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19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
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35 IUPHAR
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44 MeSH
45 MESH via Orphanet
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49 NCI
50 NCIt
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53 NINDS
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56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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