Early childhood presentation of Czech dysplasia

Abstract

Czech dysplasia, metatarsal type is an autosomal dominant skeletal disorder that is characterized by early-onset, progressive arthritis, brachydactyly of the 3^rd and 4^th toes, and characteristic radiographic findings in patients of normal stature. Patients with Czech dysplasia typically present in late childhood or later. In the present report, whole exome sequencing identified a mutation in COL2A1 (c.823C>T, p.R275C) known to be associated with Czech dysplasia in a 3.5 year old female who had a family history of early-onset arthritis and who was asymptomatic except for prominent knees. The use of whole exome sequencing facilitated diagnosis of this rare disease (less than 15 families in the literature) in the presymptomatic period and thus enabled us to provide early anticipatory guidance and genetic counseling for the family.

Figure 1

A) Pedigree of the family described. B) Sanger sequencing results show that both the proband and her mother are heterozygous for the COL2A1 c.823C>T mutation C) Photographs of the patient, demonstrating enlarged knees and unremarkable feet, as was the case for her mother’s feet (D).

Figure 1

A) Pedigree of the family described. B) Sanger sequencing results show that both the proband and her mother are heterozygous for the COL2A1 c.823C>T mutation C) Photographs of the patient, demonstrating enlarged knees and unremarkable feet, as was the case for her mother’s feet (D).

Figure 2

Radiographs of the hands (A) and feet (B) of the proband show generalized shortening of the metacarpals and metatarsals. The proximal phalanges of the hands and feet are broad and short. The first metatarsal and the phalanges of the great toes are particularly wide. Frontal radiographs of lower extremities (C) demonstrate flattening of the distal femoral and the proximal and distal tibial epiphyses. Frontal and lateral spine radiographs in the proband (D) are normal. Radiographs of the hands (E) and feet (F) in the mother show no evidence of brachydactyly. There is evidence of generalized cartilage loss with joint space narrowing especially in the carpal and tarsal regions. In addition, there is widening of the metatarsal and phalanges of the great toe bilaterally. Frontal and lateral spine radiographs (G) in the mother show platyspondyly and Schmorl’s nodes. Frontal radiographs of the right shoulder (H) demonstrate an osteochondroma (arrow).

Figure 2

Radiographs of the hands (A) and feet (B) of the proband show generalized shortening of the metacarpals and metatarsals. The proximal phalanges of the hands and feet are broad and short. The first metatarsal and the phalanges of the great toes are particularly wide. Frontal radiographs of lower extremities (C) demonstrate flattening of the distal femoral and the proximal and distal tibial epiphyses. Frontal and lateral spine radiographs in the proband (D) are normal. Radiographs of the hands (E) and feet (F) in the mother show no evidence of brachydactyly. There is evidence of generalized cartilage loss with joint space narrowing especially in the carpal and tarsal regions. In addition, there is widening of the metatarsal and phalanges of the great toe bilaterally. Frontal and lateral spine radiographs (G) in the mother show platyspondyly and Schmorl’s nodes. Frontal radiographs of the right shoulder (H) demonstrate an osteochondroma (arrow).