SNP Shot: Genomic Insights

Cutis laxa is a group of connective tissue disorders. Connective tissue supports and strengthens muscles, joints, organs, and skin. While most cases are inherited, some are acquired, meaning they aren't caused by genetic changes. Inherited cutis laxa often shows signs in infancy or childhood, while acquired cutis laxa usually develops later in life. This summary focuses on inherited forms.

The name "cutis laxa," Latin for loose skin, describes the condition's main feature: skin that sags and lacks elasticity. This inelastic skin often hangs in folds, giving the face and body a droopy or wrinkled look. The neck, armpits, and groin may be especially affected.

Cutis laxa can also affect connective tissue in organs like the heart, blood vessels, intestines, and lungs. This can lead to heart problems and abnormalities in blood vessels, such as narrowing, bulging, or tearing. Hernias (soft protrusions) may appear in the lower abdomen (inguinal hernia) or around the belly button (umbilical hernia). Diverticula, small sacs, can form in the walls of organs like the bladder and intestines. Some children with cutis laxa develop emphysema, a chronic lung disease that causes breathing difficulties. The severity of cutis laxa varies widely, depending on which organs and tissues are affected, ranging from mild to life-threatening.

Different types of cutis laxa exist, often classified by their inheritance pattern: autosomal dominant, autosomal recessive, or X-linked. Autosomal recessive forms generally cause more severe symptoms than autosomal dominant forms, though some individuals with autosomal dominant cutis laxa are severely affected. In addition to the core features, people with autosomal recessive cutis laxa might experience delayed development, intellectual disability, seizures, movement problems, or abnormalities in the eyes or bones.

The X-linked form of cutis laxa, known as occipital horn syndrome, is considered a milder type of Menkes syndrome, a condition affecting copper levels in the body. Besides sagging and inelastic skin, occipital horn syndrome includes calcium deposits in the occipital bone (at the base of the skull), coarse hair, and loose joints.

Other rare conditions like arterial tortuosity syndrome, geroderma osteodysplastica, and RIN2 syndrome are sometimes linked to cutis laxa due to the presence of loose, sagging skin. Each of these conditions has its own unique set of symptoms affecting different tissues and systems.

Inheritance:

Cutis laxa can be inherited in an autosomal dominant, autosomal recessive, or X-linked recessive manner.

Autosomal dominant inheritance means that only one copy of the mutated gene is needed in each cell to cause the disorder. Most cases of this type are due to changes in the ELN gene. Rarely, mutations in the FBLN5 or ALDH18A1 genes can also cause autosomal dominant cutis laxa.

Autosomal recessive forms of cutis laxa can be caused by mutations in the FBLN5, EFEMP2, LTBP4, ATP6V0A2, PYCR1, and ALDH18A1 genes. Autosomal recessive inheritance means that both copies of the gene in each cell must be mutated for the disorder to develop. Individuals with autosomal recessive conditions inherit one mutated copy from each parent, who are typically carriers without symptoms.

Occipital horn syndrome has an X-linked recessive inheritance pattern. It is caused by mutations in the ATP7A gene, located on the X chromosome. Males, with only one X chromosome, will develop the condition if they inherit one mutated copy. Females, with two X chromosomes, need mutations in both copies of the gene to be affected. Because this is less likely, X-linked recessive disorders are more common in males than females. A key feature of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.