Last updated:
November 04, 2020
Years published: 1986, 1988, 1994, 1997, 2005, 2020
NORD gratefully acknowledges Tasnia Rahman, MDCM Candidate, McGill University School of Medicine, and Dr. Maria Rosaria D’Apice, Medical Genetics Laboratory, University of Vergata, Rome, Italy, for assistance in the preparation of this report.
Summary
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.
Introduction
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.
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.
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.
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.
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.
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.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/ All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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Some current clinical trials also are posted on the following page on the NORD website:
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TEXTBOOKS
Hoeger P, Kinsler V, Yan A, et al. Harper’s Textbook of Pediatric Dermatology. 4th ed. John Wiley & Sons Ltd., Hoboken, NJ. 2019:1731-2.
Schachner LA, Hansen RC. Pediatric Dermatology. 4th ed. Elsevier Ltd., Philadelphia, PA. 2011:529.
Royce PM, Steinmann B. Connective Tissue and Its Heritable Disorders. 2nd ed. Wiley-Liss, Inc., New York, NY. 2002:464-65.
JOURNAL ARTICLES
Maroofian R, Murdocca M, Rezaei-Delui H, et al. A novel in-frame deletion in ZMPSTE24 is associated with autosomal recessive acrogeria (gottron type) in an extended consanguineous family. Clin Dysmorph. 2018;27(3):88-90. https://pubmed.ncbi.nlm.nih.gov/29595749/.
Hadj-Rabia S, Mashiah J, Roll P, et al. A new lamin a mutation associated with acrogeria syndrome. J Invest Dermatol. 2014;134(8):2274-2277. https://pubmed.ncbi.nlm.nih.gov/24687084/.
Sanghi S, Grewal RS, Vasudevan B, Nagure A. A rare case of acrogeria. Med J Armed Forces India. 2013; 69(4):406-408. https://pubmed.ncbi.nlm.nih.gov/24600155/.
Hashimoto C, Abe M, Onozawa N, Yokoyama Y, Ishikawa O. Acrogeria (Gottron type): a vascular disorder?. Br J Dermatol. 2004; 151(2):497-501. https://pubmed.ncbi.nlm.nih.gov/15327562/.
Blaszczyk M, Depaepe A, Nuytinck L, et al. Acrogeria of the gottron type in a mother and son. Eur J Dermatol. 2000;10:36-40. https://pubmed.ncbi.nlm.nih.gov/10694296/.
Rezai-delui H, Lotfi N, Mamoori G, et al. Hereditary gottron’s acrogeria with recessive transmission: a report of four cases in one family. Pediatr Radiol. 1999;29:124-30.
Greally JM, Boone LY, Lenkey SG, et al. Acrometageria: a spectrum of premature aging syndromes. Am J Med Genet. 1992; 44:334-39. https://pubmed.ncbi.nlm.nih.gov/1488981/.
INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Acrogeria, gottron type (201200). Johns Hopkins University, Baltimore, MD; 1966-2020. Updated August 5, 2018. https://www.omim.org/entry/201200. Accessed August 28, 2020.
Acrogeria, gottron type. Genetic and Rare Diseases Information Center. Updated June 19, 2020. https://rarediseases.info.nih.gov/diseases/6543/acrogeria-gottron-type. Accessed August 28, 2020.
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