A 28 year-old woman G2 P0 (previous history of early spontaneous abortion), was referred for a second opinion about an "abnormal skull".
The father was 32 year-old. No medical history, personal or familial. No consanguinity.
The first scan at 13 week had been considered normal, with normal nuchal translucency (NT 1,5 mm / CRL 69 mm).

The following images were obtained in from second trimester fetus. The head demonstrated a cloverleaf skull, frontal bossing, proptosis

Radiohumeral ankylosis was seen at the level of the arm, the thumb and toes are broad.

Abnormal vertebrae.

The most striking features were :

1. craniosynostosis with
2. cloverleaf skull and
3. severe ocular proptosis.

Searching OMIM for "cloverleaf, proptosis†provided us with 4 entries of which PFEIFFER comes second. Searching "Pfeiffer†on TheFetus.net led to the probable diagnosis of Pfeiffer and the subtype II.

According to Smith's Recognizable Patterns of Human Malformation, among craniosynostosis syndromes, Pfeiffer syndrome (Acrocephalosyndactyly, Brachycephaly, Mild Syndactyly, Broad Thumbs and Toes) is characterized by:

Craniofacial anomalies

• craniosynostosis,
• full high forehead,
• hypertelorism,
• small nose with low nasal bridge

Hands and feet anomalies

• broad thumb and great toe

Occasional abnormalities

• cloverleaf skull,
• radiohumeral ankylosis / synostosis of elbow,
• fused vertebrae

Some of these findings give significant indications about the prognosis: affected patients with type II and III die early with severe CNS involvement.

So the diagnostic clues for Pfeiffer type II were:

• cloverleaf skull,
• severe proptosis,
• elbow synostosis,
• broad thumb and great toes,
• abnormal vertebrae.

We (Levy, Gourand) hadn't seen a Pfeiffer case "live†before. By using OMIM and TheFetus.net on the spot in the examination room, we were able to look immediately for the significant findings (which were not obvious at first sight i.e.: elbow, thumb, vertebrae) and to conclude our report in a few minutes with the diagnosis of Pfeiffer type II which was confirmed later by the pathologist. FGFR2 is being investigated.

A karyotype 45, XX,t(13q14q) was found by chance. This robertsonian translocation has no relation with the Pfeiffer syndrome.

After counseling, the parents chose to have an interruption of the pregnancy.

The fetus after delivery: The same findings can be observed:

The radiohumeral fusion, and abnormal vertebrae:

Conclusion: Pfeiffer syndrome  type II