About juberg-marsidi syndrome

What is juberg-marsidi syndrome?

Juberg-Marsidi syndrome is an extremely rare X-linked genetic disorder that is fully expressed in males only, and is apparent at birth (congenital) or during the first few weeks of life (neonatal period). Affected children exhibit severe mental retardation; delays in reaching developmental milestones (e.g., crawling, walking, etc.); muscle weakness; diminished muscle tone (hypotonia); and/or delayed bone growth as well as growth retardation, resulting in short stature.

Affected infants also exhibit hearing loss; underdevelopment of the genitals (microgenitalism); and/or abnormalities of the head and facial (craniofacial) area such as an abnormally small head (microcephaly), a flat (depressed) nasal bridge, eye (ocular) abnormalities, and/or, in some cases, additional physical abnormalities. The range and severity of symptoms may vary from case to case. Juberg-Marsidi syndrome is inherited as an X-linked recessive trait.

What are the symptoms for juberg-marsidi syndrome?

Delayed bone growth symptom was found in the juberg-marsidi syndrome condition

Physical findings and symptoms associated with JMS are fully present in males only and the range and severity of symptoms vary from person to person. The primary findings include abnormalities in the urinary tract and reproductive organs (urogenital abnormalities), short stature/delayed growth, and craniofacial abnormalities. Affected children also exhibit severe intellectual disability; delays in reaching developmental milestones (e.g., crawling, walking, etc.); muscle weakness; and Diminished muscle tone (hypotonia). They may also have hearing loss; underdevelopment of the genitals (microgenitalism); malformations of hands and feet; and/or abnormalities of the head and facial (craniofacial) area. Craniofacial features include an abnormally Small head (microcephaly), a flat or depressed nasal bridge, an upward slant in the opening between the eyelids (upslanting palpebral fissures), Eye abnormalities such as increased distance between the eyes (orbital hypertelorism) and a prominent forehead.

Some females who carry a single copy of the disease gene (heterozygous carriers) may exhibit milder symptoms such as low cognitive ability/IQ and/or microcephaly.

A full list of notable symptoms include:

Head and Neck

  • Abnormally Small head (microcephaly)
  • Underdevelopment of the region about the nose and mouth (midfacial hypoplasia)
  • Prominent forehead


  • Widely spaced eyes (telecanthus or orbital hypertelorism)
  • Fold of the eyelid at the inner edge (epicanthic fold)
  • Crossed eyes (strabismus)
  • Upward slanting of the space between the eyelids (upslanting palpebral fissures)
  • Eye misalignment in which one or both of the eyes turn outward (exotropia)
  • Visual impairment or Blindness as a result of the above ocular symptoms


  • Small triangular nose with prominent upward pointed nostrils
  • Flat or depressed nasal bridge


  • Broad mouth with a large tongue that often protrudes
  • Abnormally located and developed teeth


  • Flaccid, weak muscles with diminished tone from the time of birth (neonatal hypotonia)
  • Muscle Stiffness and uncontrolled involuntary muscle movements (spasticity)
  • Motor impairments in some individuals (inability to walk)
  • Convulsive Seizures in some individuals
  • Clubbed feet in one affected child

Urogenital System Signs of hypogonadism (hypogenetalism) including:

  • Underdeveloped or small scrotum (external genital hypoplasia)
  • Undescended (cryptorchidism) or very small testicles
  • Small penis (micropenis)

Growth and Development

  • Intellectual disability
  • Delayed skeletal maturation and bone growth
  • Short stature
  • Low birth weight
  • Delays in reaching developmental milestones (e.g., crawling, sitting, walking, etc.)


  • Failure to thrive as an infant
  • Sensorineural deafness due to nerve damage or underdevelopment of the nerves in the ear
  • Difficulty talking or being unable to speak
  • Malformed and discolored fingernails and/or toenails (onychodystrophy)
  • Hormonal deficiencies such as pituitary gonadotropin deficiency (e.g. low response to LHRH

What are the causes for juberg-marsidi syndrome?

The gene that causes Juberg-Marsidi syndrome is located on the X chromosome and is called the HUWE1 gene.

When the disease is present, the HUWE1 gene has undergone a missense mutation. The missense mutation leads to one of the building blocks of protein (amino acid) to be incorrectly exchanged for another, which creates an abnormal protein. There are numerous different HUWE1 missense mutations recorded and they affect a process called protein ubiquitination. This process involves modifying numerous proteins in order to mediate a variety of cell functions. There are three main enzymes that work in protein ubiquitination; E1, E2, and E3. E3 is called ubiquitin ligase and is the final step in the process. The HUWE1 gene makes a specific E3 ubiquitin ligase. Mutations in HUWE1 may result in decreased expression of the protein and abnormal enzyme function, which could affect protein ubiquitination. Little is known about the direct relationship between specific HUWE1 mutations and the physical manifestations of the disease, but this is being studied in a mouse model.

JMS is inherited in an X-linked recessive pattern. X-linked genetic disorders are conditions caused by a non-working gene on the X chromosome and manifest mostly in males. Females that have a non-working gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes, one normal X chromosome and one X chromosome that carries the non-working gene. Males have one X chromosome that is inherited from their mother. If a male inherits an X chromosome that contains a non-working gene, he will develop the disease.

With each pregnancy, female carriers of an X-linked disorder have a 25% chance to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease, and a 25% chance to have an unaffected son.

If a male with an X-linked disorder is able to reproduce, he will pass the non-working gene to all of his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.

What are the treatments for juberg-marsidi syndrome?

The treatment of this syndrome is directed toward the specific symptoms that are apparent in each individual and focused on supporting patients. Treatment requires the coordinated efforts of a team of specialists. Pediatricians, speech pathologists, nutritionists, specialists who assess and treat hearing problems (audiologists), eye specialists, urologists and other health care professionals may need to systematically and comprehensively plan an affected child’s treatment.

Urogenital symptoms indicate an increased need for kidney and renal function monitoring because of a possible increased risk for kidney swelling (hydronephrosis) caused by urine accumulation or recurrent urinary tract infections.

A variety of methods may be used to treat and correct eye abnormalities. Surgery, corrective glasses, or contact lenses may be used to help improve vision. In some cases, hearing aids may be used for those with hearing impairment. Early intervention is important in ensuring that affected children with JMS reach their potential. Special services that may be beneficial to affected children may include special remedial education and other medical, social, and/or vocational services.

Genetic counseling is recommended for affected individuals and their families.

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