T-cell immunodeficiency, congenital alopecia and nail dystrophy

Other Names: FOXN1 deficiency; Severe T-cell immunodeficiency-congenital alopecia-nail dystrophy syndrome; Winged helix deficiency; Severe combined immunodeficiency due to FOXN1 deficiency; Congenital alopecia and nail dystrophy associated with severe functional T-cell immunodeficiency; Pignata Guarino syndrome; Alymphoid cystic thymic dysgenesis

T-cell immunodeficiency, congenital alopecia, and nail dystrophy is a type of severe combined immunodeficiency (SCID), which is a group of disorders characterized by an almost total lack of immune protection from foreign invaders such as bacteria and viruses.

People with this form of SCID are missing functional immune cells called T cells, which normally recognize and attack foreign invaders to prevent infection. Without functional T cells, affected individuals develop repeated and persistent infections starting early in life. The infections result in slow growth and can be life-threatening; without effective treatment, most affected individuals live only into infancy or early childhood.

Epidemiology

T-cell immunodeficiency, congenital alopecia, and nail dystrophy is a rare disorder. It has been diagnosed in only a few individuals, almost all of whom are members of a large extended family from a community in southern Italy.

Cause

T-cell immunodeficiency, congenital alopecia, and nail dystrophy results from mutations in the FOXN1 gene. This gene provides instructions for making a protein that is important for development of the skin, hair, nails, and immune system. Studies suggest that this protein helps guide the formation of hair follicles and the growth of fingernails and toenails. The FOXN1 protein also plays a critical role in the formation of the thymus, which is a gland located behind the breastbone where T cells mature and become functional. Researchers suspect that the FOXN1 protein is also involved in the development of the central nervous system, although its role is unclear. Mutations in the FOXN1 gene prevent cells from making any functional FOXN1 protein. Without this protein, hair and nails cannot grow normally. A lack of FOXN1 protein also prevents the formation of the thymus. When this gland is not present, the immune system cannot produce mature, functional T cells to fight infections. As a result, people with T-cell immunodeficiency, congenital alopecia, and nail dystrophy develop recurrent serious infections starting early in life.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. However, some people who carry one copy of a mutated FOXN1 gene have abnormal fingernails or toenails.

Signs and symptoms

T-cell immunodeficiency, congenital alopecia, and nail dystrophy also affects growth of the hair and nails. Congenital alopecia refers to an absence of hair that is apparent from birth. Affected individuals have no scalp hair, eyebrows, or eyelashes. Nail dystrophy is a general term that describes malformed fingernails and toenails; in this condition, the nails are often ridged, pitted, or abnormally curved. Researchers have described abnormalities of the brain and spinal cord (central nervous system) in at least two cases of this condition. However, it is not yet known whether central nervous system abnormalities are a common feature of T-cell immunodeficiency, congenital alopecia, and nail dystrophy.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 80%-99% of people have these symptoms

• Congenital alopecia totalis
• Immunodeficiency(Decreased immune function)
• Nail pits(Nail pitting)
• Ridged nail(Grooved nails)
• T lymphocytopenia(Low T cell count)

Diagnosis

Immunologic investigations shows decreased numbers of T cells with poor proliferative response to phytohemagglutinin (PHA) and variable hypogammaglobulinemia. Molecular Genetics Tests include:

• Targeted variant analysis
• Deletion/duplication analysis
• Sequence analysis of the entire coding region

Management

Patients with FOXN1 mutations may not respond well to hematopoietic stem cell transplantation, and it is not curative. Thymic transplantation offers a potential cure.

NIH genetic and rare disease info

• NIH info on T-cell immunodeficiency, congenital alopecia and nail dystrophy

T-cell immunodeficiency, congenital alopecia and nail dystrophy is a rare disease.