Immunodeficiency-Centromeric Instability-Facial Anomalies Syndrome 3

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

Homozygosity of CDCA7 [1] (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 [2]).

Treatment

Treatment Options:

No effective treatment has been reported.

References

Article Title:

Mutations in CDCA7 and HELLS cause immunodeficiency-centromeric instability-facial anomalies syndrome [3]

Thijssen PE, Ito Y, Grillo G, Wang J, Velasco G, Nitta H, Unoki M, Yoshihara M, Suyama M, Sun Y, Lemmers RJ, de Greef JC, Gennery A, Picco P, Kloeckener-Gruissem B, Gungor T, Reisli I, Picard C, Kebaili K, Roquelaure B, Iwai T, Kondo I, Kubota T, van Ostaijen-Ten Dam MM, van Tol MJ, Weemaes C, Francastel C, van der Maarel SM, Sasaki H. Mutations in CDCA7 and HELLS cause immunodeficiency-centromeric instability-facial anomalies syndrome. Nat Commun. 2015 Jul 28;6:7870.

PubMed ID:

26216346

Unknown syndrome: ischiadic hypoplasia, renal dysfunction, immunodeficiency, and a pattern of minor congenital anomalies [4]

Braegger C, Bottani A, Halle F, Giedion A, Leumann E, Seger R, Willi U, Schinzel A. Unknown syndrome: ischiadic hypoplasia, renal dysfunction, immunodeficiency, and a pattern of minor congenital anomalies. J Med Genet. 1991 Jan;28(1):56-9.

PubMed ID:

1999836