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Acro-cardio-facial syndrome

General Information (adopted from Orphanet):

Synonyms, Signs:	ACROCARDIOFACIAL SYNDROME CCGE ACFS CCGE syndrome Cleft palate - cardiac defect - genital anomalies - ectrodactyly
Number of Symptoms	57
OrphanetNr:	2008
OMIM Id:	600460
ICD-10:	Q87.8
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence:	9 cases [Orphanet]
Inheritance:	Autosomal recessive [Orphanet]
Age of onset:	Antenatal Neonatal [Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases:

Multiple congenital anomalies/dysmorphic syndrome-intellectual deficit
-Rare developmental defect during embryogenesis
-Rare genetic disease
Orofacial clefting syndrome
-Rare developmental defect during embryogenesis
-Rare genetic disease
-Rare maxillo-facial surgical disease
-Rare otorhinolaryngologic disease
Rare genetic intellectual deficit with developmental anomaly
-Rare genetic disease
Rare intellectual deficit with developmental anomaly
-Rare neurologic disease

Symptom Information: Sort by abundance

	Symptom Information	Symptom	Abundance	DB Freq
1	(HPO:0000049)	Shawl scrotum		31 / 7739
2	(HPO:0000028)	Cryptorchidism		347 / 7739
3	(HPO:0000054)	Micropenis	Frequent [Orphanet]	257 / 7739
4	(HPO:0000035)	Abnormality of the testis	Frequent [Orphanet]	296 / 7739
5	(HPO:0000047)	Hypospadias	Frequent [Orphanet]	250 / 7739
6	(HPO:0000316)	Hypertelorism	Frequent [Orphanet]	644 / 7739
7	(HPO:0000499)	Abnormality of the eyelashes	Frequent [Orphanet]	35 / 7739
8	(HPO:0000348)	High forehead	Frequent [Orphanet]	157 / 7739
9	(HPO:0000520)	Proptosis	Occasional [Orphanet]	192 / 7739
10	(HPO:0000174)	Abnormality of the palate	Frequent [Orphanet]	298 / 7739
11	(HPO:0000431)	Wide nasal bridge	Frequent [Orphanet]	290 / 7739
12	(HPO:0000204)	Cleft upper lip	Frequent [Orphanet]	193 / 7739
13	(HPO:0000175)	Cleft palate		349 / 7739
14	(HPO:0008589)	Hypoplastic helices		2 / 7739
15	(HPO:0000400)	Macrotia		108 / 7739
16	(HPO:0000357)	Abnormal location of ears	Very frequent [Orphanet]	328 / 7739
17	(HPO:0000369)	Low-set ears		372 / 7739
18	(HPO:0001249)	Intellectual disability		1089 / 7739
19	(HPO:0001276)	Hypertonia	Occasional [Orphanet]	317 / 7739
20	(HPO:0001263)	Global developmental delay		853 / 7739
21	(HPO:0001250)	Seizures	Occasional [Orphanet]	1245 / 7739
22	(HPO:0000836)	Hyperthyroidism	Occasional [Orphanet]	25 / 7739
23	(HPO:0001829)	Foot polydactyly	Occasional [Orphanet]	41 / 7739
24	(HPO:0001163)	Abnormality of the metacarpal bones	Frequent [Orphanet]	149 / 7739
25	(HPO:0001171)	Split hand		72 / 7739
26	(HPO:0100490)	Camptodactyly of finger	Occasional [Orphanet]	212 / 7739
27	(HPO:0004060)	Trident hand	Very frequent [Orphanet]	13 / 7739
28	(HPO:0001770)	Toe syndactyly	Occasional [Orphanet]	149 / 7739
29	(HPO:0100257)	Ectrodactyly		27 / 7739
30	(HPO:0001217)	Clubbing		39 / 7739
31	(HPO:0001822)	Hallux valgus	Occasional [Orphanet]	70 / 7739
32	(HPO:0001373)	Joint dislocation	Occasional [Orphanet]	59 / 7739
33	(HPO:0006101)	Finger syndactyly	Occasional [Orphanet]	198 / 7739
34	(HPO:0001839)	Split foot	Frequent [Orphanet]	28 / 7739
35	(HPO:0002023)	Anal atresia	Occasional [Orphanet]	135 / 7739
36	(HPO:0004325)	Decreased body weight	Very frequent [Orphanet]	492 / 7739
37	(HPO:0001511)	Intrauterine growth retardation	Frequent [Orphanet]	358 / 7739
38	(HPO:0001510)	Growth delay		295 / 7739
39	(HPO:0012303)	Abnormality of the aortic arch	Occasional [Orphanet]	57 / 7739
40	(HPO:0001636)	Tetralogy of Fallot	Occasional [Orphanet]	104 / 7739
41	(HPO:0001660)	Truncus arteriosus	Occasional [Orphanet]	21 / 7739
42	(HPO:0030680)	Abnormality of cardiovascular system morphology		355 / 7739
43	(HPO:0001680)	Coarctation of aorta		57 / 7739
44	(HPO:0004960)	Absent pulmonary artery		5 / 7739
45	(HPO:0001631)	Atria septal defect	Occasional [Orphanet]	274 / 7739
46	(HPO:0001629)	Ventricular septal defect	Occasional [Orphanet]	316 / 7739
47	(HPO:0001643)	Patent ductus arteriosus		228 / 7739
48	(HPO:0001633)	Abnormality of the mitral valve	Occasional [Orphanet]	69 / 7739
49	(HPO:0001252)	Muscular hypotonia	Occasional [Orphanet]	990 / 7739
50	(OMIM)	Clubbing of the digits		1 / 7739
51	(HPO:0012758)	Neurodevelopmental delay	Very frequent [Orphanet]	949 / 7739
52	(HPO:0003819)	Death in childhood		42 / 7739
53	(HPO:0011420)	Death	Frequent [Orphanet]	184 / 7739
54	(OMIM)	Absence of the pulmonary artery		1 / 7739
55	(HPO:0001522)	Death in infancy	Occasional [Orphanet]	275 / 7739
56	(HPO:0000007)	Autosomal recessive inheritance		2538 / 7739
57	(HPO:0002120)	Cerebral cortical atrophy	Frequent [Orphanet]	187 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol	Variation	Clinical significance	Reference

Additional Information:

Clinical Description OMIM

Richieri-Costa and Orquizas (1987) reported the case of a Brazilian boy, born to healthy, consanguineous parents, who was affected by a constellation of malformations including ectrodactyly, cleft lip/palate, congenital heart defect, genital anomalies, and mental retardation. Giannotti et ... Richieri-Costa and Orquizas (1987) reported the case of a Brazilian boy, born to healthy, consanguineous parents, who was affected by a constellation of malformations including ectrodactyly, cleft lip/palate, congenital heart defect, genital anomalies, and mental retardation. Giannotti et al. (1995) reported a brother and sister, offspring of nonconsanguineous parents, with the same combination of cleft palate, cardiac defect, genital anomalies, and ectrodactyly (CCGE). They suggested that this is an autosomal recessive disorder. Guion-Almeida et al. (2000) reported a male patient with a constellation of malformations, including cleft lip/palate, abnormal ears, ectrodactyly, congenital heart defect (coarctation of the aorta and a patent ductus arteriosus; see 607411), delayed psychologic development, and growth retardation that was prenatal in origin. The patient died at 4 months of age. CT scan of the brain showed cerebral atrophy and enlarged cisterna magna. Guion-Almeida et al. (2000) proposed the name acrocardiofacial syndrome for this condition. Mingarelli et al. (2005) reported an affected male infant who died at age 1 month from cardiorespiratory failure. He was hypotonic with mild facial dysmorphism, including high forehead, broad nasal bridge and bulbous nasal tip, slight hypertelorism, long and thin high-arched palate, and receding chin. Ears were low-set with thin upper helices, prominent and vertical anthelices, and large lobes. He had hypoplastic scrotum and cryptorchidism. There was a cleft right hand with agenesis of the third finger. X-ray studies showed multiple abnormalities, including a digitalized first finger, splitting of the proximal third digit phalanx, unilateral split foot malformation with partially fused fourth and fifth toes and with absence of all phalanges of the second and third toes. There were 11 rib pairs. Echocardiography showed ventricular septal defect, truncus arteriosus, and stenotic truncal valve. In a literature review of patients with CCGE, Mingarelli et al. (2005) noted that ectrodactyly was the main common characteristic, and they emphasized the extreme clinical variability of the disorder. Tanpaiboon et al. (2009) reported a 14-year-old Thai boy with cleft lip and palate, congenital cardiac defects, including ventricular septal defect, tetralogy of Fallot, and absent left pulmonary artery, and ectrodactyly of the left hand with absence of the second and third finger. Dysmorphic features included hypertelorism, protruding ears, and hypoplastic lower crus of the antihelices. He also had poor growth, clubbing of the fingers and toes, shawl scrotum, micropenis, and moderate mental retardation. Unusual features included mild scoliosis, hemivertebrae, and subclinical hyperthyroidism. Genetic analysis excluded pathogenic mutations in the coding region of the TP63 gene (603273).

Symptoms & Signs

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