Case report

This patient had been referred to our hospital after a doubt on abnormal face on 3rd trimester ultrasound screening. Previous personal, familial and obstetrical history was non-relevant for malformations nor for infectious diseases.Our US examination at 32 weeks of pregnancy revealed the following anomalies.

We performed an additional fetal CT and fetal brain MRI, looking for additional anomalies at this late term.

Our initial prenatal diagnosis was a cleidocranial dysplasia, which is the most frequent syndrome encountered with clavicle hypoplasia and wide skull sutures. This disease bears an orthopedic-only prognosis. We also thought about pycnodysostosis, which was less likely.

Amniocentesis was performed and caryotype was normal, as well as the CGH-array. The baby has been delivered at 38 weeks of pregnancy. Failure to thrive was a pejorative element non-consistent with cleidocranial dysplasia. Clinical examination by the geneticist paediatrician concluded the diagnosis of Yunis-Varon syndrome.

Videos 1 and 2; images 1, 2 and 3: videos and images show abnormal face with an unusual large and wide philtrum, and a retrognatism. Tongue is not protruding but is close to the lips. Thumb agenesis was seen and the other digits were short.

The external ears were also small (not shown).

Images 4, 5, 6 and 7: CT scan images show abnormal hypomineralisation of the skull and facial bones.

Sutures were absent or wide. Maxillary bones could not be identified. Also bilateral clavicle hypoplasia, with slender shape, and thumb phalanges agenesis were seen. Hands were short due to agenesis of the distal phalanges of the 4 other digits.

Images 8, 9, 10 and 11: MR images shown no brain structural anomalies. However, face examination revealed hypertelorism, abnormal thick upper lip, and retrognatism (inferior facial angle =51° (<60°); while superior facial angle was normal = 131° (135°+/-5°).

Images 12-20: Postnatal skeletal X-ray examination revealed hypomineralisation of the skull and facial bones, agenesis of the thumb bones and agenesis of the distal phalanges on both hands and feet.

Additional anomalies unseen prenatally : agenesis of the ascending ramus of the mandible, hence retrognatism; likely cervical platyspondyly; abnormal acetabular roofs; right-sided spine on the iliac bone and many bony callus suggesting past fractures of the long bones.

Yunis-Varon syndrome is a severe autosomal recessive disorder characterized by skeletal defects, including cleidocranial dysplasia and digital anomalies, and severe neurologic involvement with neuronal loss.

Enlarged cytoplasmic vacuoles are found in neurons, muscle, and cartilage. 
The disorder is usually lethal in infancy.

Hypoplasia or aplasia of the clavicles may lead to discuss the following differential diagnoses:
-Cleidocranial dysplasia: usually no neurological impairement
-Pycnodysostosis: diffuse bone sclerosis however with acro-osteolysis and clavicle osteolysis. Fractures are common. No neurological impairement.
-Trisomy 13 or 18
-Acromandibular syndrome: usually no neurological impairement, ectodermal anomalies mimicking progeria condition featured in “fast-aging” syndromes.
-Yunis-Varon syndrome: severe failure to thrive, Aplastic/hypoplastic thumbs and halluces might be a strong suggestive feature.

References

COW #400: https://sonoworld.com/TheFetus/Case.aspx?CaseId=3560&answer=1

Basel-Vanagaite, L., Kornreich, L., Schiller, O., Yacobovich, J., Merlob, P. Yunis-Varon syndrome: further delineation of the phenotype. Am. J. Med. Genet. 146A: 532-537, 2008. [PubMed: 18203163]

Pfeiffer, R. A., Diekmann, L., Stock, H. J. Aplasia of the thumbs and great toes as the outstanding feature of Yunis and Varon syndrome: a new entity, a new observation. Ann. Genet. 31: 241-243, 1988. [PubMed: 3265308]

Yunis, E., Varon, H. Cleidocranial dysostosis, severe micrognathism, bilateral absence of thumbs and first metatarsal bone, and distal aphalangia: a new genetic syndrome. Am. J. Dis. Child. 134: 649-653, 1980. [PubMed: 7395825