Presentation
Doubt on abnormal face on 3rd trimester ultrasound screening (according to French screening policy). Previous personal, familial and obstetrical history is non-relevant for malformations nor infectious diseases.
Patient Data
Video1, Image 1&2: abnormal face with an unusually large and wide philtrum, and a retrognathism. The tongue is not protruding but close to the lips.
Video2, image 3: Thumb agenesis. Other digits are short.
The external ears were also small (not shown).
- abnormal hypomineralisation of the skull and facial bones.
- sutures are absent or wide.
- axillary bones cannot be identified.
- bilateral clavicle hypoplasia, with slender shape.
- agenesis of thumb phalanges.
- short hands due to agenesis of the distal phalanges of the other four digits.
No brain anomalies, normal brain biometry, morphology and signal.
However, face examination reveals hypertelorism, an abnormal thick upper lip, and retrognathism (inferior facial angle =51° (<60°); while the superior facial angle is normal = 131° (135°+/-5°).
As properly diagnosed prenatally:
- hypomineralisation of the skull and facial bones
- agenesis of the thumb bones
- agenesis of the distal phalanges on both hands and feet.
Additional anomalies unseen prenatally:
- agenesis of the ascending ramus of the mandible, hence retrognathism
- cervical platyspondyly
- abnormal acetabular roofs
- right-sided spine on the iliac bone
- many bony callus suggesting past fractures of the long bones.
Case Discussion
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 karyotype was normal, as well as the comparative genomic hybridization (CGH-array).
The baby has been delivered at 38 weeks of gestation naturally.
Failure to thrive was a pejorative element non-consistent with cleidocranial dysplasia. Clinical examination by the geneticist pediatrician concluded to a Yunis-Varón syndrome.
Yunis-Varón 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 impairment.
- pycnodysostosis: diffuse bone sclerosis however with acro-osteolysis and clavicle osteolysis. Fractures are common. No neurological impairment.
- trisomy 13 or 18.
- acromandibular syndrome: usually no neurological impairment, ectodermal anomalies mimicking progeria condition featured in “fast-aging” syndromes.
- Yunis-Varón syndrome: severe failure to thrive, aplastic/hypoplastic thumbs and halluces might be a strong suggestive feature 4
Drs Cuillier, Balu and Alessandri also contributed to this case.