Yunis-Varon syndrome

Joseph R Siebert PhD (Dr. Siebert of the University of Washington has no relevant financial relationships to disclose.)
Harvey B Sarnat MD FRCPC MS, editor. (Dr. Sarnat of the University of Calgary has no relevant financial relationships to disclose.)
Originally released January 26, 1996; last updated August 24, 2017; expires August 24, 2020

This article includes discussion of Yunis-Varon syndrome and cleidocranial dysostosis. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

Yunis-Varon syndrome (“cleidocranial dysostosis”) is a rare, generally severe, and autosomal recessive condition manifested by numerous anomalies of the craniofacial complex (dolichocephaly, wide fontanelles, sparse hair, hypoplastic facial bones, thin lips, short philtrum, micrognathia, and variable changes of the CNS, including eyes), small/absent clavicles, small/absent thumbs and great toes, and other anomalies. Mutations in FIG4 have been identified in several unrelated or consanguineous families; a biallelic mutation in VAC14 has been identified in a single neonate with normal FIG4 sequencing. The syndrome continues to undergo phenotypic and molecular delineation.

Key points

 

• Major phenotypic changes in this rare congenital disorder involve the clavicles and head (cleidocranial dysostosis), mandible, and distal limbs.

 

• Craniocerebral anomalies include poor growth of cranial bones, macrocephaly, large fontanels, and cortical malformations (eg, polymicrogyria).

 

• Neurologic symptoms and craniofacial findings may include hypotonia and weakness, psychomotor delay, large, dysplastic ears, and cleft lip and palate. Seizures and psychiatric manifestations are recognized as well.

 

• Cardiorespiratory failure commonly leads to death in the neonatal period, although survival into the second decade has been reported.

 

• Familial recurrence, sometimes with a history of consanguinity, has suggested autosomal recessive inheritance in the past, and is supported by the finding of FIG4 mutations in several families.

Historical note and terminology

In 1980, Yunis and Varon described an infant boy and 4 infant girls from 3 Colombian families; 1 family had a single affected infant, and the other 2 families each had 2 affected infants. The patients had multiple malformations, including cleidocranial dysostosis, severe micrognathism, and hypoplasia or aplasia of metatarsal bones, phalanges, or thumbs. Changes in the cranium consisted mainly of “skull dysostosis,” characterized by wide fontanelles and separated sutures, craniofacial disproportion, macrocrania, hypoplastic facial bones, and micrognathia. Clavicular changes included uniform absence of the right clavicle and hypoplasia or absence of the left clavicle. All died before the age of 10 weeks. In 2 of the families, consanguinity was reported. The authors postulated that this was a new recessively inherited syndrome (Yunis and Varon 1980). In 1983, Hughes and Partington reported a 4.25-year-old boy with the same pattern of malformations, shortness of stature, and mental retardation; they referred to the condition as “the syndrome of Yunis and Varon” (Hughes and Partington 1983).

Additional cases have been described with similar findings and some new features (Partington 1988; Pfeiffer et al 1988; Hennekam and Vermeulen-Meiners 1989; Garrett et al 1990; Ades et al 1993; Dworzak et al 1995; Rabe et al 1996; Christie et al 1999; Walch et al 2000). Rabe and colleagues added a note that their patient had a sister with features of Yunis-Varon but did not describe her (Rabe et al 1996). The patient described by Partington had cardiomyopathy (Partington 1988), and Ades and colleagues described a patient with congenital heart malformations (tetralogy of Fallot) (Ades et al 1993). The patient reported by Dworzak and colleagues was a female with generalized lysosomal storage (Dworzak et al 1995). A female baby of German origin had a severe hearing impairment between 1000 Hz and 8000 Hz, detected by auditory evoked potential studies (Rabe et al 1996). Christie and colleagues described a 28-year-old woman with multiple anomalies interpreted as Yunis-Varon syndrome (although the morphology of the clavicle was not described). By a variety of imaging techniques, the woman had atrophy of the left lobe of the liver and an anomalous dilated hepatic vessel at the junction of right and left lobes. Vascular compromise of the left lobe was suggested, but the patient was lost to follow-up before additional studies could be performed (Christie et al 1999). Walch and colleagues reported a 15-week-old female infant with Yunis-Varon syndrome with microcephaly, hydrocephalus, and Dandy-Walker malformation. Severe neurologic impairment associated with intraneuronal inclusions and vacuolar degeneration has been taken as evidence for a lysosomal storage disorder (Walch et al 2000). However, the patient reported by Sumi and colleagues showed no evidence for such a disorder (Sumi et al 2004).

The content you are trying to view is available only to logged in, current MedLink Neurology subscribers.

If you are a subscriber, please log in.

If you are a former subscriber or have registered before, please log in first and then click select a Service Plan or contact Subscriber Services. Site license users, click the Site License Acces link on the Homepage at an authorized computer.

If you have never registered before, click Learn More about MedLink Neurology  or view available Service Plans.