The IVIC syndrome: A new autosomal dominant complex pleiotropic syndrome with radial ray hypoplasia, hearing impairment, external ophthalmoplegia, and thrombocytopenia

Abstract

The IVIC syndrome is an autosomal dominant condition affecting mainly the upper limbs. It is described from 19 living members of one family of mostly Caucasoid descent; it came to Venezuela from the Canary Islands 140 years ago. The new mutation appeared six generations ago. It has complete penetrance and wide expressivity for a radial ray defect which may vary from an almost normal thumb to a severely malformed upper limb. When present, the thumb has a long/slender metacarpal and a short distal phalanx, reflected in a typical metacarpophalangeal (MP) pattern profile. Anthropometry reveals delayed growth in the forearms, clavicles, and cranium during adolescence, and permanently in the spine; the maturation of the face, tibiae, and feet is normal. The radial carpal bones are always affected, some being still hypoplastic at advanced ages. Constant palmar dermatoglyphic anomalies are a high a-b ridge count, a distally placed or absent t triradius, and an increased frequency of patterns in the second interdigital area. Extraocular muscles are involved almost always, producing strabismus. Hearing is bilaterally impaired due to a mixed congenital loss, either total or partial. Mild thrombocytopenia and leukocytosis are present before the age of 50 years. There is neither associated ectodermal dysplasia nor heart involvement [except for occasional mild, incomplete right bundle branch block (IRBBB)]; imperforate anus occurs in about 10% of affected persons. The possible pathogenetic relationship to the thalidomide embryopathy and to the Holt-Oram syndrome, among others, is discussed.

IVIC syndrome Is caused by a c.2607delA mutation in the SALL4 locus

“…Since the first report by Crisp (1918) on familial aggregation of the Duane anomaly, many other reports of inherited radial ray malformations and oculomotor disturbances have been published [Ferrell et al, 1966;Temtamy et al, 1975;Okihiro et al, 1977;Arias et al, 1980, Hayes et al, 1985Temtamy, 1986]. The underlying gene remained unknown until recently, when two independent groups identified mutations in SALL4 as the cause for the same syndrome sensu lato [Al-Baradie et al, 2002;Kohlhase et al, 2002a].…”

“…Occasionally there were alterations in spine, scapular girdle, and kidney malrotation, imperforate anus or rectovaginal fistula. Lower limbs were always normal [Arias et al, 1980]. Thumb involvement was the most typical finding varying from absence hypoplasia, to the presence of a triphalangic thumb.…”

Radial ray aplasia and renal anomalies in father and son: A new syndrome

“…In both of them an external ear anomaly was also present. The association between radial ray and [Quan and Smith, 1973;Arias et al, 1980;Nilsson, 1960;Rohz, 1949;Siegler, Larson, and Buehler, 19801. In FA 27% of homozygotes have a renal anomaly, half being a solitary kidney.…”

“…Aplasia or hypoplasia of the radial ray can occur per se or as part of certain syndromes of genetic or nongenetic origin [Arias et al, 1980;Nilsson, 1960;Pruzanski, 19641. Some of the syndromes are autosomal dominant (the Holt-Oram [Pruzanski, 19641 or the IVIC [Arias et al, 19801 syndrome) or recessive (FA [Nilsson, 19601 TAR [Landing, 19751 syndrome traits.…”

Prenatal Two- and Three-Dimensional Ultrasound Diagnosis of Limb Reduction Defects Associated with Homozygous α-Thalassemia

“…Various hypotheses such as occlusion of blood vessels, prolonged intrauterine hypoxia, or deletion of genes responsible for limb embryogenesis have been postulated to explain the association of limb reduction defects in fetuses with homozygous ␣ -thalassemia [9][10] . Limb defects may also occur in other disorders such as Fanconi anemia [11] , thrombocytopenia and absent radius syndrome [12] , Aase-Smith syndrome [13] , Diamond-Blackfan syndrome [14] , WT syndrome [15] , IVIC syndrome [16] , Shokeir syndrome [17] , DKphocomelia syndrome [18] , Schlegelberger syndrome [19] , and congenital dyserythropoietic anemia type I [20] .…”