Clinical Guidance

Genotype-phenotype correlations indicate that the amount of residual activity of the sulfate transporter modulates the phenotype in this spectrum of disorders that extends from lethal ACG1B to mild SLC26A2-related multiple epiphyseal dysplasia (SLC26A2-MED). Homozygosity or compound heterozygosity for pathogenic variants predicting stop codons or structural variants in transmembrane domains of the sulfate transporter are associated with ACG1B, while pathogenic variants located in extracellular loops, in the cytoplasmic tail of the protein, or in the regulatory 5'-flanking region of the gene result in less severe phenotypes .

Source: GeneReviews — "Achondrogenesis Type 1B"

Diagnostic Criteria

Achondrogenesis type 1B (ACG1B) is a perinatal-lethal disorder with death occurring prenatally or shortly after birth.

Suggestive Findings

ACG1B should be suspected in individuals with the following clinical and radiographic findings.

Clinical findings

• Extremely short limbs with short fingers and toes and clubfeet

• Hypoplasia of the thorax

• Protuberant abdomen

• Hydropic fetal appearance caused by the abundance of soft tissue relative to the short skeleton

• Flat face with micrognathia

• Short neck

• Thickened soft tissue of the neck

Radiographic findings. While the degree of ossification generally depends on gestational age, variability can be observed between radiographs taken at similar gestational ages; thus, no single feature should be considered obligatory.

Source: GeneReviews — "Achondrogenesis Type 1B"

Differential Diagnosis

Achondrogenesis type 1B (ACG1B) should be distinguished from other lethal chondrodysplasias and severe osteochondrodysplasias.

Table 3.

Selected Disorders in the Differential Diagnosis of Achondrogenesis Type 1B

Gene | MOI | Disorder | Key Features

Achondrogenesis1

TRIP11

| AR | ACG1A (Houston-Harris type) (OMIM 200600) | Rib fractures absence of ossification of vertebral pedicles may suggest ACG1A. Hands fingers are less markedly shortened than in ACG1B. Cartilage matrix is normal inclusions are present in chondrocytes.

COL2A1

| AD | ACG2 (Langer-Saldino type) (See Type II Collagen Disorders Overview.) | Hands fingers can be almost normal. ACG2 shows more severe underossification of vertebral bodies than ACG1B, typical configuration of iliac bones w/concave medial inferior borders, nonossificatio...

Source: GeneReviews — "Achondrogenesis Type 1B"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease in an individual diagnosed with achondrogenesis type 1B (ACG1B), the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 4. Recommended Evaluations Following Initial Diagnosis in Individuals with Achondrogenesis Type 1B

Source: GeneReviews — "Achondrogenesis Type 1B"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions.

Source: GeneReviews — "Achondrogenesis Type 1B"