Acrocardiofacial syndrome

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

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.

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.

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.

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.

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 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.

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.

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.

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.

Life expectancy is very low. Most reported patients survived only a few hours or months. Cardiopulmonary complications were the main cause of death.

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Last updated: 12/1/2010

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