Which are the causes of Focal Dermal Hypoplasia?

Focal Dermal Hypoplasia (FDH), also known as Goltz syndrome, is a rare genetic disorder that primarily affects the skin, skeleton, eyes, and face. It is caused by mutations in the PORCN gene, which is responsible for producing a protein essential for embryonic development.

The main cause of FDH is a mutation in the PORCN gene. This gene is located on the X chromosome, and FDH follows an X-linked dominant inheritance pattern. This means that the condition is more common in females, as they have two X chromosomes, while males have only one. However, males with the mutation often experience more severe symptoms.

The PORCN gene mutation leads to a deficiency of the PORCN protein. This protein plays a crucial role in the Wnt signaling pathway, which is involved in various developmental processes. The Wnt signaling pathway regulates the growth and differentiation of cells during embryonic development, and its disruption can lead to abnormalities in multiple organs and tissues.

The deficiency of the PORCN protein affects the development of different body systems. In FDH, it primarily affects the skin, causing hypoplasia (underdevelopment) of the dermis. This results in characteristic skin abnormalities, such as atrophic patches, streaks, and papillomas. The skin may also be thin, fragile, and prone to blistering.

FDH can also affect the skeletal system. Individuals with FDH may have skeletal abnormalities, including asymmetry, limb defects, and short stature. They may also experience joint laxity, scoliosis, and abnormalities in the fingers and toes.

The eyes and face are commonly affected in FDH. Ocular manifestations can include coloboma (a gap or split in the structures of the eye), microphthalmia (abnormally small eyes), and other eye abnormalities. Facial features may be dysmorphic, with notched or missing areas of the skin, small chin, and thin lips.

Other organs and systems can also be involved in FDH. These may include the teeth, nails, hair, gastrointestinal tract, cardiovascular system, and genitourinary system. The severity and specific manifestations can vary widely among individuals.

It is important to note that FDH is a genetic disorder, and the mutation in the PORCN gene is present from birth. However, the symptoms and severity can vary significantly, even among affected individuals within the same family.

Diagnosis of FDH is typically based on clinical features and genetic testing to identify the specific mutation in the PORCN gene. Management of FDH involves a multidisciplinary approach, addressing the specific symptoms and complications that arise in each affected individual.