Gottron Syndrome

 Gottron Syndrome

OVERVIEW

Gottron syndrome is an extremely rare inherited disorder characterized by a premature aged appearance (progeroid), especially in the form of unusually fragile, thin skin on the hands and feet (distal extremities). Although the disorder is most typically recognized in early childhood, these characteristic skin findings are present from birth.

Gottron syndrome is described as a mild, nonprogressive, congenital form of skin atrophy due to the loss of the fatty tissue directly under the skin (subcutaneous atrophy). This causes the skin to have a dry and transparent appearance. The affected individual is often noted to have hollow cheeks, a beaked nose, and owl-like eyes. Other findings may include abnormally small hands and feet with unusually prominent veins on the chest; irregular hyperpigmentation of the skin (poikiloderma); thinned hair (alopecia); small stature; and/or abnormally small jaw (micrognathia).

Characteristics that develop later in life may include premature senility, endocrine disturbances and cataracts. Gottron syndrome may either be inherited in an autosomal dominant or autosomal recessive pattern. Approximately 50 patients have been reported in medical literature.

Gottron syndrome was first described by Heinrich Gottron in 1940. There is some debate in the literature regarding a possible relationship between Gottron syndrome and vascular type Ehlers-Danlos syndrome (formerly type IV). Some clinicians believe the terms are synonymous. Others disagree.

SYMPTOMS

The signs and symptoms of Gottron syndrome vary somewhat from one person to another. Because this condition is so rare, it is difficult to get a complete picture of the core features that define the syndrome.

Generally, from birth-onwards, children with Gottron syndrome appear older than their actual age. The skin is unusually thin, taut, and parchment-like on the hands and feet (distal extremities) and may even involve the face. The hands and feet remain abnormally small into adulthood. Those affected by Gottron syndrome are said to have a characteristic face defined by a pinched looking face, hollow cheeks, an owl-eyed appearance, a beaked nose and thin lips.

The veins on the chest are very visible and prominent (telangiectasia) due to diminished amounts of fat under the skin (subcutaneous fat). There may also be discoloration of the skin (poikiloderma) or easy bruising especially on the legs and the chest. However, while mostly it is reported that nails appear normal, there have been some reports of a thickened appearance (dystrophic). The affected individual may also have fine or thinning hair (alopecia).

Certain skeletal defects may be evident as well. These may include delayed cranial suture closure. The newborn’s skull is comprised of separate bony plates which are separated by sutures. This allows for transient distortion during birth and permits for growth of the brain in the first two years of life. Normally these bony plates will end up fusing by the age of two. Other skeletal defects include bone reabsorption of the ends of the fingers and toes (acro-osteolysis) as well as recurrent fractures.

Gottron syndrome is a non-progressive disorder, so the symptoms do not tend to get worse over time. The prognosis is generally quite good and affected individuals have average intelligence as well as a normal life expectancy. Although some patients develop heart disease similar to other premature aging diseases (progeria), people with Gottron syndrome do not usually have the associated premature heart disease.

CAUSES

Gottron syndrome is a rare disorder that for which the mode of inheritance is still not well understood. There is evidence for both autosomal recessive and autosomal dominant inheritance patterns. Most often, a child with Gottron syndrome is the only affected person in the family.

Recessive genetic disorders occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.

Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of mutated (changed gene) in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy.

While not yet well understood, there have been reports that Gottron syndrome may arise due to changes (mutations) in the LMNA, ZMPSTE24, or COL3A1 genes.

AFFECTED POPULATIONS

It is believed that Gottron syndrome may affect more females than males. While about 50 affected individuals have been reported in the medical literature, the exact number of people with this condition is unknown.

DISORDERS WITH SIMILAR SYMPTOMS

Symptoms of the following disorders can be similar to those of Gottron syndrome. Comparisons may be useful for a differential diagnosis:

De Barsy syndrome is a rare genetic disorder characterized by a prematurely-aged appearance (progeroid) as well as skin that is loose and lacking elasticity (cutis laxa).The appearance of the infant appears prematurely aged-due to the underdevelopment of the skin and structures of the face (facial hypoplasia) which is further enhanced by wrinkled and saggy skin. Other notable facial features include a prominent forehead, thin lips, and large ears. This is often accompanied by eye abnormalities, intellectual disability as well as growth delays. Affected infants may also have diminished muscle tone (hypotonia). Signs and symptoms of de Barsy syndrome are usually evident in early infancy if not at birth. (For more information on this disorder, choose “De Barsy syndrome” as your search term in the Rare Disease Database.)

Hutchinson-Gilford progeria syndrome is a severe form of premature aging (progeria). In early infancy, children with progeria most often have a normal appearance. However, beyond the age of nine months affected children appear as though they are rapidly aging and experience growth delays resulting in very short stature. They may further develop characteristic facial features such as a relatively large head, small face, beak-like nose, a small jaw (micrognathia) and a receding chin. By the age of two, often scalp hair, eyebrows and eyelashes are either lost completely or replaced by pale hairs. Children with Hutchinson-Gilford syndrome usually have normal intelligence, but their life span is shortened due to heart disease (atherosclerosis). (For more information on this disorder, choose “Hutchinson-Gilford Progeria as your search term in the Rare Disease Database.)

Werner syndrome is a rare progressive disorder that is characterized by the appearance of unusually accelerated aging (progeria). Although the disorder is typically recognized by the third or fourth decades of life, certain characteristic findings are present in childhood, adolescence, and early adulthood and the condition is most often diagnosed before puberty. Children with Werner syndrome have an abnormally slow growth rate, and growth ends at puberty. As a result, affected individuals have unusually short stature and low weight even relative to height. By age 25, those with the disorder typically experience early graying and premature loss of scalp hair (alopecia). As the disease progresses, additional abnormalities include loss of the layer of fat beneath the skin (subcutaneous adipose tissue); severe wasting (atrophy) of muscle tissue in certain areas of the body; and degenerative skin changes, particularly in the facial area, the upper arms and hands, and the lower legs and feet. Due to degenerative changes affecting the facial area, individuals with Werner syndrome may have unusually prominent eyes, a beaked or pinched nose, and/or other characteristic facial abnormalities. (For more information on this disorder, choose “Werner syndrome” as your search term in the Rare Disease Database.)

DIAGNOSIS

Typically, Gottron syndrome is diagnosed through a clinical examination once other more common conditions have been initially excluded. Genetic testing may further aid in the diagnosis process.

STANDARD THERAPIES

Treatment

Treatment for Gottron syndrome is symptomatic and supportive. The management team involved in the care of someone with Gottron syndrome may include a dermatologist, orthopedist and/or a medical geneticist.

Type of Doctor Department :Dermatologist