Definition

This is a heterogeneous group of disorders characterized by increased bone density due to insufficient bone resorption resulting from osteoclast dysfunction. The most common causes are TCIRG1 (about 50 to 58% of autosomal recessive cases) and CLCN7 (about 13 to 16%). The infantile malignant form usually begins before age 2; it presents with anemia, thrombocytopenia, hepatosplenomegaly, and vision/hearing loss, and can be fatal before age 10 in untreated cases.

Gene/region examined

TCIRG1 - Exon 2, TCIRG1 - Exon 3, TCIRG1 - Exon 4, TCIRG1 - Exon 5, TCIRG1 - Exon 6, TCIRG1 - Exon 7, TCIRG1 - Exon 8, TCIRG1 - Exon 9, TCIRG1 - Exon 10, TCIRG1 - Exon 11, TCIRG1 - Exon 12, TCIRG1 - Exon 13, TCIRG1 - Exon 14, TCIRG1 - Exon 15, TCIRG1 - Exon 16, TCIRG1 - Exon 17, TCIRG1 - Exon 18, TCIRG1 - Exon 19, TCIRG1 - Exon 20

Method

Sequence analysis

Accepted sample types

EDTA blood, AF, CVS

Inheritance

Hereditary; most commonly autosomal recessive (infantile malignant form), but CLCN7 variants can also lead to autosomal dominant forms.

Related Tests

Inheritance Patterns

Describes how a genetic condition is passed on within a family. There are five main patterns

Go to term →

Carrier (Heterozygous / Homozygous)

Why it matters: In autosomal recessive inheritance, when each parent is a carrier (while both appear healthy), the chance of their child being born with the disease is 25% in each

Go to term →

VUS (Variant of Uncertain Significance)

This is the situation where the test has detected a change in the DNA, but the role of this change in the development of disease is unconfirmed.

Go to term →

How to Read a Genetic Test Result (Positive / Negative / VUS)

A genetic test result falls into three main categories

Go to term →

Types of Genetic Tests

A genetic test is a type of medical test that detects changes in genes, chromosomes or proteins. Today there are more than 77,000 genetic tests available.

Go to term →