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Disease Profile

Acrocardiofacial syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Neonatal

ICD-10

Q87.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Cleft palate, Cardiac defect, Genital anomalies, and Ectrodactily; CCGE syndrome; Cleft palate-cardiac defect-genital anomalies-ectrodactyly syndrome;

Summary

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

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.

Visit the Orphanet disease page for more resources.

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Feeding difficulties in infancy
0008872
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Low-set ears
Low set ears
Lowset ears

[ more ]

0000369
Split hand
Claw hand
Claw hand deformities
Claw hands
Claw-hand deformities
Split-hand

[ more ]

0001171
30%-79% of people have these symptoms
Abnormality of the metacarpal bones
Abnormality of the long bone of hand
0001163
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Cleft palate
Cleft roof of mouth
0000175
Cleft upper lip
Harelip
0000204
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
High forehead
0000348
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Hypoplasia of penis
Underdeveloped penis
0008736
Hypospadias
0000047
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation

[ more ]

0001511
Long eyelashes
Increased length of eyelashes
Unusually long eyelashes

[ more ]

0000527
Split foot
Lobster-claw foot deformity
Split-foot

[ more ]

0001839
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge

[ more ]

0000431
5%-29% of people have these symptoms
Anal atresia
Absent anus
0002023
Atrial septal defect
An opening in the wall separating the top two chambers of the heart
Hole in heart wall separating two upper heart chambers

[ more ]

0001631
Camptodactyly of finger
Permanent flexion of the finger
0100490
Coarctation of aorta
Narrowing of aorta
Narrowing of the aorta

[ more ]

0001680
Death in infancy
Infantile death
Lethal in infancy

[ more ]

0001522
Finger syndactyly
0006101
Foot polydactyly
Duplication of bones of the toes
0001829
Hallux valgus
Bunion
0001822
Hyperthyroidism
Overactive thyroid
0000836
Hypertonia
0001276
Joint dislocation
Joint dislocations
Recurrent joint dislocations

[ more ]

0001373
Mitral stenosis
0001718
Muscular hypotonia
Low or weak muscle tone
0001252
Proptosis
Bulging eye
Eyeballs bulging out
Prominent eyes
Prominent globes
Protruding eyes

[ more ]

0000520
Seizure
0001250
Tetralogy of Fallot
0001636
Toe syndactyly
Fused toes
Webbed toes

[ more ]

0001770
Truncus arteriosus
0001660
Urogenital fistula
0100589
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
Percent of people who have these symptoms is not available through HPO
Absent pulmonary artery
Absent lung artery
0004960
Autosomal recessive inheritance
0000007
Clubbing
Clubbing of fingers and toes
0001217
Death in childhood
0003819
Global developmental delay
0001263
Growth delay
Delayed growth
Growth deficiency
Growth failure
Growth retardation
Poor growth
Retarded growth

[ more ]

0001510
Hypoplastic helices
0008589
Macrotia
Large ears
0000400
Micropenis
Short penis
Small penis

[ more ]

0000054
Patent ductus arteriosus
0001643
Shawl scrotum
Scrotum surrounds penis
0000049

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.