ACFS
MCID: CLF044
MIFTS: 30

Cleft Palate, Cardiac Defect, Genital Anomalies, and Ectrodactyly (ACFS)

Categories: Cardiovascular diseases, Fetal diseases, Neuronal diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Cleft Palate, Cardiac Defect, Genital Anomalies, and...

MalaCards integrated aliases for Cleft Palate, Cardiac Defect, Genital Anomalies, and Ectrodactyly:

Name: Cleft Palate, Cardiac Defect, Genital Anomalies, and Ectrodactyly 57 70
Acrocardiofacial Syndrome 57 20 58
Acfs 57 20 58
Cleft Palate-Cardiac Defect-Genital Anomalies-Ectrodactyly Syndrome 20 58
Ccge Syndrome 20 58
Cleft Palate, Cardiac Defect, Genital Anomalies, and Ectrodactily 20
Acrocardiofacial Syndrome; Acfs 57
Acro-Cardio-Facial Syndrome 20
Ccge 57

Characteristics:

Orphanet epidemiological data:

58
acrocardiofacial syndrome
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal; Age of death: any age;

OMIM®:

57 (Updated 20-May-2021)
Miscellaneous:
death in childhood
six patients have been reported (as of july 2011)

Inheritance:
autosomal recessive


HPO:

31
cleft palate, cardiac defect, genital anomalies, and ectrodactyly:
Onset and clinical course death in infancy death in childhood
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


Summaries for Cleft Palate, Cardiac Defect, Genital Anomalies, and...

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 2008 Definition A rare genetic disorder characterized by split-hand/split-foot malformation (SHFM), facial anomalies, cleft lip /palate, congenital heart defect (CHD), genital anomalies, and intellectual deficit. Epidemiology The incidence of ACFS has not been determined due to the low number of reported cases (9 to date). A similar occurrence among genders is expected. Clinical description The spectrum of defects occurring in ACFS is wide, and both interindividual variability and clinical differences among sibs have been reported. Bilateral or unilateral cleft hand is a constant feature. Cleft foot and cutaneous finger and toe syndactyly have been reported in some cases. Congenital heart defects of varying types have been detected in two thirds of patients. Facial anomalies are not specific for the syndrome, and clinical expression appears to be variable. Male patients manifest different genital anomalies, ranging from micropenis to cryptorchidism and hypospadias. Growth retardation is a common prenatal and postnatal finding. The frequency of intellectual deficit in ACFS is at present unknown due to the early death of most patients. Neurological anomalies such as hypotonia, hypertonia, and seizures have been reported in the first days and months of life. Etiology The genetic mechanism underlying ACFS is still unknown. Isolated or syndromic SHFM has been linked to different loci or genes. Mutations in the p63 gene, responsible for ectrodactyly - ectodermal dysplasia - cleft lip palate (EEC) syndrome (see this term) and related disorders with SHFM, have been excluded in a patient with ACFS. Diagnostic methods Diagnosis is based solely on clinical characteristics. The major diagnostic criteria include SHFM and CHD. Cleft lip/palate and genital anomalies are less common features. Although facial anomalies are not specific to this disorder, low-set dysmorphic ears appear to be a constant feature. Differential diagnosis Differential diagnosis includes other ectrodactyly syndromes and clefting conditions associated with genital anomalies. However, EEC syndrome, Rapp-Hodgkin syndrome (see these terms) and ectrodactyly-cleft lip/palate-hand/foot deformities-intellectual deficit can be ruled out based on lack of ectodermal involvement. Malpuech syndrome (see this term) can also be excluded based on distinct facial features and absent limb defects. CHD, cleft palate, and genital anomalies are features of genito-palato-cardiac syndrome, but none of the reported cases had ectrodactyly. Antenatal diagnosis The major features of ACFS can be detected prenatally by ultrasonography. A second trimester scan, including echocardiography and upper/lower limb evaluation, is recommended for monitoring pregnancies when parents have had a child with the disorder. Genetic counseling ACFS follows an autosomal recessive pattern of inheritance. The risk of transmitting the disease for the parents of an affected child seems to be up to 1 in 4. Management and treatment Patients are at high risk of death in the first months of age. Cardiac and respiratory problems should be treated by specialists. A nutrition specialist should be consulted for feeding problems. Surviving patients will benefit from physical therapy, which should start in the first months of life in babies manifesting hypotonia/hypertonia and motor delays. In surviving patients, neuropsychological assessment should be performed every year to check for developmental and cognitive delay. Prognosis Life expectancy is very low. Most reported patients survived only a few hours or months. Cardiopulmonary complications were the main cause of death.

MalaCards based summary : Cleft Palate, Cardiac Defect, Genital Anomalies, and Ectrodactyly, also known as acrocardiofacial syndrome, is related to cleft palate, isolated and split-hand/foot malformation 1. The drugs Paclitaxel and Cisplatin have been mentioned in the context of this disorder. Affiliated tissues include heart and brain, and related phenotypes are intellectual disability and feeding difficulties in infancy

More information from OMIM: 600460

Related Diseases for Cleft Palate, Cardiac Defect, Genital Anomalies, and...

Diseases related to Cleft Palate, Cardiac Defect, Genital Anomalies, and Ectrodactyly via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 11)
# Related Disease Score Top Affiliating Genes
1 cleft palate, isolated 10.4
2 split-hand/foot malformation 1 10.4
3 isolated split hand-split foot malformation 10.4
4 alacrima, achalasia, and mental retardation syndrome 10.3
5 anus, imperforate 10.1
6 autosomal recessive disease 10.1
7 microcephaly 10.1
8 scoliosis 9.9
9 hyperthyroidism 9.9
10 cleft lip 9.9
11 cleft lip/palate 9.9

Graphical network of the top 20 diseases related to Cleft Palate, Cardiac Defect, Genital Anomalies, and Ectrodactyly:



Diseases related to Cleft Palate, Cardiac Defect, Genital Anomalies, and Ectrodactyly

Symptoms & Phenotypes for Cleft Palate, Cardiac Defect, Genital Anomalies, and...

Human phenotypes related to Cleft Palate, Cardiac Defect, Genital Anomalies, and Ectrodactyly:

58 31 (show all 48)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 hallmark (90%) Very frequent (99-80%) HP:0001249
2 feeding difficulties in infancy 58 31 hallmark (90%) Very frequent (99-80%) HP:0008872
3 low-set ears 58 31 hallmark (90%) Very frequent (99-80%) HP:0000369
4 split hand 58 31 hallmark (90%) Very frequent (99-80%) HP:0001171
5 hypertelorism 58 31 frequent (33%) Frequent (79-30%) HP:0000316
6 wide nasal bridge 58 31 frequent (33%) Frequent (79-30%) HP:0000431
7 cleft palate 58 31 frequent (33%) Frequent (79-30%) HP:0000175
8 cryptorchidism 58 31 frequent (33%) Frequent (79-30%) HP:0000028
9 intrauterine growth retardation 58 31 frequent (33%) Frequent (79-30%) HP:0001511
10 cerebral cortical atrophy 58 31 frequent (33%) Frequent (79-30%) HP:0002120
11 cleft upper lip 58 31 frequent (33%) Frequent (79-30%) HP:0000204
12 hypospadias 58 31 frequent (33%) Frequent (79-30%) HP:0000047
13 high forehead 58 31 frequent (33%) Frequent (79-30%) HP:0000348
14 hypoplasia of penis 58 31 frequent (33%) Frequent (79-30%) HP:0008736
15 abnormality of the metacarpal bones 58 31 frequent (33%) Frequent (79-30%) HP:0001163
16 long eyelashes 58 31 frequent (33%) Frequent (79-30%) HP:0000527
17 split foot 58 31 frequent (33%) Frequent (79-30%) HP:0001839
18 hypertonia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001276
19 atrial septal defect 58 31 occasional (7.5%) Occasional (29-5%) HP:0001631
20 coarctation of aorta 58 31 occasional (7.5%) Occasional (29-5%) HP:0001680
21 anal atresia 58 31 occasional (7.5%) Occasional (29-5%) HP:0002023
22 tetralogy of fallot 58 31 occasional (7.5%) Occasional (29-5%) HP:0001636
23 urogenital fistula 58 31 occasional (7.5%) Occasional (29-5%) HP:0100589
24 proptosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000520
25 joint dislocation 58 31 occasional (7.5%) Occasional (29-5%) HP:0001373
26 hyperthyroidism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000836
27 ventricular septal defect 58 31 occasional (7.5%) Occasional (29-5%) HP:0001629
28 truncus arteriosus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001660
29 foot polydactyly 58 31 occasional (7.5%) Occasional (29-5%) HP:0001829
30 hallux valgus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001822
31 finger syndactyly 58 31 occasional (7.5%) Occasional (29-5%) HP:0006101
32 camptodactyly of finger 58 31 occasional (7.5%) Occasional (29-5%) HP:0100490
33 toe syndactyly 58 31 occasional (7.5%) Occasional (29-5%) HP:0001770
34 mitral stenosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0001718
35 seizure 31 occasional (7.5%) HP:0001250
36 hypotonia 31 occasional (7.5%) HP:0001252
37 seizures 58 Occasional (29-5%)
38 muscular hypotonia 58 Occasional (29-5%)
39 global developmental delay 31 HP:0001263
40 macrotia 31 HP:0000400
41 growth delay 31 HP:0001510
42 micropenis 31 HP:0000054
43 patent ductus arteriosus 31 HP:0001643
44 death in infancy 58 Occasional (29-5%)
45 shawl scrotum 31 HP:0000049
46 clubbing 31 HP:0001217
47 hypoplastic helices 31 HP:0008589
48 absent pulmonary artery 31 HP:0004960

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Head And Neck Eyes:
hypertelorism

Genitourinary Internal Genitalia Male:
cryptorchidism

Genitourinary External Genitalia Male:
micropenis
hypospadias
shawl scrotum

Cardiovascular Vascular:
patent ductus arteriosus
coarctation of the aorta
absence of the pulmonary artery

Neurologic Central Nervous System:
mental retardation
delayed development

Head And Neck Mouth:
cleft palate
cleft lip

Head And Neck Ears:
low-set ears
hypoplastic helices
large ears

Cardiovascular Heart:
tetralogy of fallot
ventricular septal defect
congenital heart defects

Skeletal Hands:
ectrodactyly
clubbing of the digits

Growth Other:
poor growth

Clinical features from OMIM®:

600460 (Updated 20-May-2021)

Drugs & Therapeutics for Cleft Palate, Cardiac Defect, Genital Anomalies, and...

Drugs for Cleft Palate, Cardiac Defect, Genital Anomalies, and Ectrodactyly (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 34)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Paclitaxel Approved, Vet_approved Phase 2 33069-62-4 36314
2
Cisplatin Approved Phase 2 15663-27-1 84093 441203 2767
3
Cetuximab Approved Phase 2 205923-56-4 56842117 2333
4
Fluorouracil Approved Phase 2 51-21-8 3385
5
Ursodeoxycholic acid Approved, Investigational Phase 2 128-13-2 31401
6
Sulindac Approved, Investigational Phase 2 38194-50-2 5352 1548887
7
Aspirin Approved, Vet_approved Phase 2 50-78-2 2244
8 Tubulin Modulators Phase 2
9 Antineoplastic Agents, Immunological Phase 2
10 Immunosuppressive Agents Phase 2
11 Antimitotic Agents Phase 2
12 Immunoglobulins Phase 2
13 Albumin-Bound Paclitaxel Phase 2
14 Immunologic Factors Phase 2
15 Antibodies Phase 2
16 Antibodies, Monoclonal Phase 2
17 Antimetabolites Phase 2
18 Cathartics Phase 2
19 Polyethylene glycol 3350 Phase 2
20 Laxatives Phase 2
21 Cola Phase 2
22 Gastrointestinal Agents Phase 2
23 Fibrinolytic Agents Phase 2
24 Antirheumatic Agents Phase 2
25 Platelet Aggregation Inhibitors Phase 2
26 Anti-Inflammatory Agents Phase 2
27 Cyclooxygenase Inhibitors Phase 2
28 Analgesics Phase 2
29 Anti-Inflammatory Agents, Non-Steroidal Phase 2
30 Antipyretics Phase 2
31 Analgesics, Non-Narcotic Phase 2
32
Rifampicin Approved 13292-46-1 5458213 5381226
33 Charcoal
34 Carbon Fiber

Interventional clinical trials:

(show all 11)
# Name Status NCT ID Phase Drugs
1 Phase II Trial of Nab-Paclitaxel, Cisplatin, and 5-FU (ACF) as Induction Therapy Followed by Definitive Concurrent Chemoradiation for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (HNSCC) Completed NCT01566435 Phase 2 paclitaxel albumin-stabilized nanoparticle formulation;Cisplatin;Fluorouracil;Cetuximab
2 Polyethylene Glycol for ACF Reduction and Biomarker Modulation in Individuals With CRC Risk Completed NCT00828984 Phase 2 macrogol 3350-based oral osmotic laxative
3 Phase II Study Of Colorectal ACF Screening, Regression And Prevention In High Risk Participants Terminated NCT00062023 Phase 2 Acetylsalicylic acid (Aspirin);Sulindac;Ursodiol
4 Improving Ultrasound Images in Brain Tumour Surgery With the Use of an Acoustic Coupling Fluid Mimicking Brain Tissue: a Phase II Technical and Safety Study Terminated NCT03181581 Phase 2
5 Comparative Effectiveness/Implementation of TB Case Finding in Rural South Africa Unknown status NCT02808507
6 The Clinical Application and Efficacy Verification of an Innovative Carbon Fiber Dressing Completed NCT01921725
7 Colonoscopic Biomarkers for Cancer Risk Assessment and Prevention Completed NCT00623883
8 A Comparison of Clinic Outcomes Between Early Physical Therapy Intervention and Usual Care in Individuals Following Anterior Cervical Fusion Completed NCT01519115
9 Evaluation of the Effectiveness and Impact of Community Case Management of Severe Acute Malnutrition Through Lady Health Workers As Compared To a Facility Based Program: A Cluster Randomized Controlled Trial Completed NCT03043352
10 Benefits of a Household WASH Package to Community-based Management of Acute Malnutrition (CMAM) Program, Chad Completed NCT02486523
11 Ultrasound Imaging in Brain Tumour Surgery With the Use of SonoClear Acoustic Coupling Fluid (ACF) Mimicking Brain Tissue Not yet recruiting NCT04734444

Search NIH Clinical Center for Cleft Palate, Cardiac Defect, Genital Anomalies, and Ectrodactyly

Genetic Tests for Cleft Palate, Cardiac Defect, Genital Anomalies, and...

Anatomical Context for Cleft Palate, Cardiac Defect, Genital Anomalies, and...

MalaCards organs/tissues related to Cleft Palate, Cardiac Defect, Genital Anomalies, and Ectrodactyly:

40
Heart, Brain

Publications for Cleft Palate, Cardiac Defect, Genital Anomalies, and...

Articles related to Cleft Palate, Cardiac Defect, Genital Anomalies, and Ectrodactyly:

# Title Authors PMID Year
1
A new observation of acro-cardio-facial syndrome substantiates interindividual clinical variability. 61 57
15937946 2005
2
An autosomal recessive syndrome of cleft palate, cardiac defect, genital anomalies, and ectrodactyly (CCGE). 61 57
7897634 1995
3
Expanding the phenotypic spectrum of acro-cardio-facial syndrome (ACFS): Exclusion of P63 mutation. 57
19606477 2009
4
Cleft lip/palate, abnormal ears, ectrodactyly, congenital heart defect, and growth retardation: definition of the acro-cardio-facial syndrome. 57
11045583 2000

Variations for Cleft Palate, Cardiac Defect, Genital Anomalies, and...

Expression for Cleft Palate, Cardiac Defect, Genital Anomalies, and...

Search GEO for disease gene expression data for Cleft Palate, Cardiac Defect, Genital Anomalies, and Ectrodactyly.

Pathways for Cleft Palate, Cardiac Defect, Genital Anomalies, and...

GO Terms for Cleft Palate, Cardiac Defect, Genital Anomalies, and...

Sources for Cleft Palate, Cardiac Defect, Genital Anomalies, and...

3 CDC
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45 MESH via Orphanet
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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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