Atelosteogenesis type 3

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.

Orpha Number: 56305

Definition

A rare skeletal dysplasia characterized by short limbs dysmorphic facies and diagnostic radiographic findings.

Epidemiology

The prevalence of AOIII is unknown. Less than 25 affected patients have been reported.

Clinical description

AOII, like AOI, is characterized by rhizomelic limb shortness, dislocated hip, knee and elbow joints, broad hands and feet with broad digits, club feet, facial dysmorphism (midface hypoplasia, micrognathia, cleft palate). Feeding problems and cardiorespiratory insufficiency are often seen in newborns. Clinical manifestations due to secondary complications past early infancy include learning and language problems and a gross motor developmental delay.

Etiology

Atelosteogenesis III results from missense mutations or small in-frame deletions in the FLNB gene reported in exons 2-5, 13 and 27-33 resulting in the translation of filamin B protein with altered biochemical properties.

Diagnostic methods

The diagnosis is established after a full skeletal x-ray survey and confirmed with genetic testing. AOIII demonstrates less delay of normal ossification compared to AOI.

Antenatal diagnosis

Prenatal diagnosis is possible by ultrasound from 20 weeks onward and by prenatal genetic testing in case of family history.

Genetic counseling

Most cases of AOIII are sporadic, but AOIII may be transmitted in an autosomal dominant manner. Affected individuals of which one of the parents presents with a milder phenotype (like Larsen syndrome) (see this term) have been reported. This is likely to be related to a somatic mosaicism in the parents for a mutation that is germline in the offspring.

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