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Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 3

OMIM ID:

autosomal recessive

Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 3

Alternate Names

ICF3

Defective Genes

CDCA7

Clinical Characteristics

Ocular Features

Patients have been described as having variable oculofacial features including epicanthal folds, hypertelorism, strabismus, and ‘tapetoretinal degeneration’.    

Systemic Features

The full phenotype is variable and unknown based on the 5 reported patients from 4 families of whom 3 were consanguineous.  Recurrent infections (especially respiratory and otitis media) seem to be among the most consistent features.  Others include intrauterine growth retardation, developmental delay including psychomotor delays, a flat midface with various anomalies, low-set ears, renal dysgenesis, polydactyly, severe agammaglobulinemia, hypospadias, and cryptorchidism.  Normal T-cell function and normal B cells are present.  Conductive hearing loss, polydactyly, and scoliosis may be features as well.  Two of the 5 reported patients with ICF3 were reported to have mental retardation.  One patient died at the age of 26 years.

Genetics

Inheritance

Homozygosity of CDCA7 (2q31.1) mutations with centromeric instability and hypomethylation of selected juxtacentromeric heterochromatin regions is responsible for this (ICF3) autosomal recessive condition.  There is genetic heterogeneity in ICF (ICF1, ICF2, ICF3, and ICF4 [see 242860).   

Pedigree

Autosomal recessive

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent.  Carriers with only one mutation, such as the parents, do not have clinical disease.  Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Image
Sample pedigree of autosomal recessive inheritance

In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.

Treatment & Management

No effective treatment has been reported.

Selected Resources

Web Resources

Publications

Displaying 1 - 2 of 2

Mutations in CDCA7 and HELLS cause immunodeficiency–centromeric instability–facial anomalies syndrome

PubMedID: 26216346

Unknown syndrome: ischiadic hypoplasia, renal dysfunction, immunodeficiency, and a pattern of minor congenital anomalies.

PubMedID: 1999836