We present a case of osteogenesis imperfecta, autosomal recessive form (type VII) (OMIM #610682).

Our imaging demonstrated the following:

• Images 1-9: Usual skull without obvious bowing under probe pressure. The chest was slightly narrow, without obvious fractures. All long bones were short and bowed, especially the femur, tibia and fibula bilaterally, and the radius and ulna on the left side. Spine had a usual appearance on ultrasound.
• Images 10-17: The CT scan demonstrated an unusual skull appearance for gestational age, which was discordant with the ultrasound findings. The calvaria appeared poorly ossified. Clavicles were normal. Chest did not appear significantly narrow, which was again discordant with the ultrasound images. There were no obvious rib fractures. The spine appeared normal without platyspondyly. The pelvis appeared normal. All long bones were short, predominantly the lower limbs (rhizo- and mesomelic parts). The femurs were bowed inwards, with the inner cortex being denser than the outer cortex. Other bones of the lower limbs were bowed as well. Hands were normal.

Our differential diagnosis had to take into account both imaging findings and clinical history (healthy parents, past intrauterine death for dwarfism):

1. Thanatophoric dwarfism (OMIM#187600) was ruled out. Even though there was marked shortness and bowing of the long bones, as well as a “French telephone receiver” aspect of both femurs, thanatophoric dwarfism is a sporadic disease. Additionally, the chest probably wasn’t narrow enough, there was no platyspondyly, and the skull appearance did not fit.
2. Osteogenesis imperfecta: Most cases are inherited in an autosomal dominant fashion, however, there are cases of autosomal recessive inheritance described in southern Africa and northern America. The autosomal recessive form is called type VII (OMIM #610682) and the impaired genetic locus differs from other forms of osteogenesis imperfecta. The poorly mineralized skull, bowed lower limbs, and absence of platyspondyly were compatible. We kept in mind Occam’s razor principle stating that a rare form of a common disease is more common than a typical form of a rare disease. Therefore we did not completely rule out osteogenesis imperfecta.
3. Kyphomelic dysplasia (OMIM #211350) or its closely related entities, Schwartz-Jampel syndrome (OMIM #255800) and Stuve-Wiedemann syndrome (OMIM #601559). All 3 conditions are inherited in an autosomal recessive fashion. They typically display a pattern of anomalies focused on the lower limbs with or without platyspondyly. There is relative sparing of the rest of the skeleton, as in our case. The aspect of the femurs, with dense inner cortex compared to the outer cortex, was also suggestive. A mild facial dysmorphism may be present. Kyphomelic dysplasia has been described prenatally, while Schwartz-Jampel syndrome and Stuve-Wiedemann syndromes are usually diagnosed postnatally in early infancy. However, all three syndromes do not normally result in intrauterine death. Kyphomelic dysplasia remained our most likely prenatal diagnosis.

The parents chose to continue the pregnancy and to deliver normally at 39 weeks of pregnancy. Postnanal examination found no facial dysmorphism, a soft skull with wide anterior fontanelle, bowed thighs with bilateral coxofemoral dislocations. There was no muscular retractions or trismus (for Schwartz-Jampel syndrome and Stuve-Wiedemann syndromes) but sucking and swallowing were difficult. The neonate experienced pain and required morphine. Postnatal x-rays (Image 17-22) demonstrated wormian skull bones, mild demineralization of the skull and the rest of skeleton, marked bowed femurs, mildly curved legs and forearms, and flared metaphyses. Interestingly, we noted bony callus on several ribs, suggesting fracture, which were retrospectively hard to assess prenatally.

Bony callus, large fontanel, wormian bones and need for morphine were the decisive elements of our final diagnosis: osteogenesis imperfecta, autosomal recessive form (type VII) (OMIM #610682). The past history of lethal dwarfism was most likely osteogenesis imperfecta,  type 7 with a more severe phenotype.

References

[1] Francomano CA, Kniffin CL. “Stuve-Wiedemann Syndrome 1; STWS1.” OMIM. https://omim.org/entry/601559, publish date 02/2022.
[2] Genin G. Anomalies Osseuses Constitutionnelles. Sauramps Medical, 11/2008. ISBN-10: 284023534X; ISBN-13: 978-2840235347
[3] McKusick VA, Kniffin CL. “Schwartz-Jampel Syndrome, Type 1; SJS1” OMIM. https://omim.org/entry/255800, publish date 3/2022.
[4] McKusick VA, Przylepa KA. “Kyphomelic Dysplasia.” OMIM. https://omim.org/entry/211350, publish date 6/2007.
[5] Przylepa KA, Sobreira N. "Osteogenesis Imperfecta, Type VII; OI7" OMIM. https://omim.org/entry/610682, publish date 10/2016.