U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Martsolf syndrome(MARTS)

MedGen UID:
208658
Concept ID:
C0796037
Disease or Syndrome
Synonyms: Cataract mental retardation hypogonadism; Congenital cataract with intellectual disability and hypogonadotropic hypogonadism syndrome; MARTS
SNOMED CT: Congenital cataract with intellectual disability and hypogonadotropic hypogonadism syndrome (722380003); Martsolf syndrome (722380003)
 
Monarch Initiative: MONDO:0023910
OMIM®: 212720
OMIM® Phenotypic series: PS212720

Disease characteristics

Excerpted from the GeneReview: RAB18 Deficiency
RAB18 deficiency is the molecular deficit underlying both Warburg micro syndrome (characterized by eye, nervous system, and endocrine abnormalities) and Martsolf syndrome (characterized by similar – but milder – findings). To date Warburg micro syndrome comprises >96% of reported individuals with genetically defined RAB18 deficiency. The hallmark ophthalmologic findings are bilateral congenital cataracts, usually accompanied by microphthalmia, microcornea (diameter <10), and small atonic pupils. Poor vision despite early cataract surgery likely results from progressive optic atrophy and cortical visual impairment. Individuals with Warburg micro syndrome have severe to profound intellectual disability (ID); those with Martsolf syndrome have mild to moderate ID. Some individuals with RAB18 deficiency also have epilepsy. In Warburg micro syndrome, a progressive ascending spastic paraplegia typically begins with spastic diplegia and contractures during the first year, followed by upper-limb involvement leading to spastic quadriplegia after about age five years, often eventually causing breathing difficulties. In Martsolf syndrome infantile hypotonia is followed primarily by slowly progressive lower-limb spasticity. Hypogonadism – when present – manifests in both syndromes, in males as micropenis and/or cryptorchidism and in females as hypoplastic labia minora, clitoral hypoplasia, and small introitus. [from GeneReviews]
Authors:
Mark Handley  |  Eamonn Sheridan   view full author information

Additional description

From MedlinePlus Genetics
RAB18 deficiency causes two conditions with similar signs and symptoms that primarily affect the eyes, brain, and reproductive system. These two conditions, called Warburg micro syndrome and Martsolf syndrome, were once thought to be distinct disorders but are now considered to be part of the same disease spectrum because of their similar features and shared genetic cause.

Warburg micro syndrome is the more severe condition. Individuals with this condition have several eye problems from birth, including clouding of the lenses of the eyes (cataracts), abnormally small eyes (microphthalmia), and small corneas (microcornea). The lens is a structure at the front of the eye that helps focus light, and the cornea is the outer covering of the eye. In addition, the pupils of the eyes may be abnormally small (constricted), and they may not enlarge (dilate) in low light. Individuals with Warburg micro syndrome also have degeneration of the nerves that carry visual information from the eyes to the brain (optic atrophy). The eye problems impair vision in affected individuals.

Neither Warburg micro syndrome nor Martsolf syndrome affect the life expectancy of affected individuals.

People with Warburg micro syndrome have severe intellectual disability and other neurological features due to problems with growth and development of the brain. Affected individuals have delayed development and may never be able to sit, stand, walk, or speak. They usually have weak muscle tone (hypotonia) in infancy. By early childhood, they develop muscle stiffness (spasticity) and joint deformities (contractures) that restrict movement in the legs. The muscle problems worsen (progress) to include the arms and lead to paralysis of all four limbs (spastic quadriplegia). Eventually, breathing may be impaired. The brain abnormalities can contribute to vision problems (cortical visual impairment). Individuals with Warburg micro syndrome may also have recurrent seizures (epilepsy).

Some people with Warburg micro syndrome have reduced production of the hormones that direct sexual development (hypogonadotropic hypogonadism). The shortage of these hormones impairs normal development of reproductive organs. Affected males may have a small penis (micropenis) or undescended testes (cryptorchidism). Affected females may have underdeveloped internal genital folds (labia minora) or a small clitoris or vaginal opening (introitus).

Martsolf syndrome affects the same body systems as Warburg micro syndrome but is usually less severe. Individuals with Martsolf syndrome have cataracts, microphthalmia, and small pupils. They have milder optic atrophy and cortical visual impairment than people with Warburg micro syndrome. Intellectual disability is mild to moderate in people with Martsolf syndrome. While language and motor skills, such as sitting and walking, are delayed, affected individuals usually acquire them. Hypotonia is common in infants with Martsolf syndrome, although spasticity worsens more slowly than in individuals with Warburg micro syndrome, and it usually affects only the legs and feet. Hypogonadotropic hypogonadism can also occur in individuals with Martsolf syndrome.  https://medlineplus.gov/genetics/condition/rab18-deficiency

Professional guidelines

PubMed

Handley MT, Morris-Rosendahl DJ, Brown S, Macdonald F, Hardy C, Bem D, Carpanini SM, Borck G, Martorell L, Izzi C, Faravelli F, Accorsi P, Pinelli L, Basel-Vanagaite L, Peretz G, Abdel-Salam GM, Zaki MS, Jansen A, Mowat D, Glass I, Stewart H, Mancini G, Lederer D, Roscioli T, Giuliano F, Plomp AS, Rolfs A, Graham JM, Seemanova E, Poo P, García-Cazorla A, Edery P, Jackson IJ, Maher ER, Aligianis IA
Hum Mutat 2013 May;34(5):686-96. doi: 10.1002/humu.22296. PMID: 23420520

Recent clinical studies

Diagnosis

Xu W, Plummer L, Quinton R, Swords F, Crowley WF, Seminara SB, Balasubramanian R
Cold Spring Harb Mol Case Stud 2020 Jun;6(3) Epub 2020 Jun 12 doi: 10.1101/mcs.a005033. PMID: 32376645Free PMC Article
Trkova M, Hynek M, Dudakova L, Becvarova V, Hlozanek M, Raskova D, Vincent AL, Liskova P
Am J Med Genet A 2016 Jul;170(7):1843-8. Epub 2016 Jun 3 doi: 10.1002/ajmg.a.37685. PMID: 27256633
Corbeel L, Freson K
Eur J Pediatr 2008 Jul;167(7):723-9. Epub 2008 May 8 doi: 10.1007/s00431-008-0740-z. PMID: 18463892Free PMC Article
Ehara H, Utsunomiya Y, Ieshima A, Maegaki Y, Nishimura G, Takeshita K, Ohno K
Am J Med Genet A 2007 May 1;143A(9):973-8. doi: 10.1002/ajmg.a.31626. PMID: 17394201
Derbent M, Agras PI, Gedik S, Oto S, Alehan F, Saatçi U
Am J Med Genet A 2004 Jul 30;128A(3):232-4. doi: 10.1002/ajmg.a.30109. PMID: 15216542

Prognosis

Bem D, Yoshimura S, Nunes-Bastos R, Bond FC, Kurian MA, Rahman F, Handley MT, Hadzhiev Y, Masood I, Straatman-Iwanowska AA, Cullinane AR, McNeill A, Pasha SS, Kirby GA, Foster K, Ahmed Z, Morton JE, Williams D, Graham JM, Dobyns WB, Burglen L, Ainsworth JR, Gissen P, Müller F, Maher ER, Barr FA, Aligianis IA
Am J Hum Genet 2011 Apr 8;88(4):499-507. doi: 10.1016/j.ajhg.2011.03.012. PMID: 21473985Free PMC Article

Clinical prediction guides

Hozhabri H, Talebi M, Mehrjardi MYV, De Luca A, Dehghani M
Am J Med Genet A 2020 May;182(5):957-961. Epub 2020 Mar 12 doi: 10.1002/ajmg.a.61543. PMID: 32162791
Trkova M, Hynek M, Dudakova L, Becvarova V, Hlozanek M, Raskova D, Vincent AL, Liskova P
Am J Med Genet A 2016 Jul;170(7):1843-8. Epub 2016 Jun 3 doi: 10.1002/ajmg.a.37685. PMID: 27256633
Bem D, Yoshimura S, Nunes-Bastos R, Bond FC, Kurian MA, Rahman F, Handley MT, Hadzhiev Y, Masood I, Straatman-Iwanowska AA, Cullinane AR, McNeill A, Pasha SS, Kirby GA, Foster K, Ahmed Z, Morton JE, Williams D, Graham JM, Dobyns WB, Burglen L, Ainsworth JR, Gissen P, Müller F, Maher ER, Barr FA, Aligianis IA
Am J Hum Genet 2011 Apr 8;88(4):499-507. doi: 10.1016/j.ajhg.2011.03.012. PMID: 21473985Free PMC Article
Temtamy SA, Sinbawy AH
Am J Med Genet 1991 Dec 15;41(4):432-3. doi: 10.1002/ajmg.1320410409. PMID: 1776632

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...