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Flashcards in Systemic & syndromes Deck (27):

what is CDG?

congenital disorder of glycosylation


what are the findings of CDG

  • inherited condition
  •  affects many parts of the body.
  • vary widely among affected individuals, sometimes even among members of the same family.
  • develop signs and symptoms during infancy.
  • may have weak
    • muscle tone (hypotonia),
    • retracted (inverted) nipples,
    • an abnormal distribution of fat, e
    •  (strabismus),
    • developmental delay,
    •  (failure to thrive).
    • Infants with PMM2-CDG also frequently have an underdeveloped cerebellum,
  • Distinctive facial features are
    • high forehead,
    • a triangular face,
    • large ears, and a
    • thin upper lip.
    • elevated liver function test results,
    • seizures,
    • About 20 percent of affected infants do not survive the first year of life due to multiple organ failure.
    • TAffected individuals may also experience stroke-like episodes that involve an extreme lack of energy (lethargy) and temporary paralysis. 
    • During adolescence or adulthood, individuals with PMM2-CDG have reduced sensation and weakness in their arms and legs (peripheral neuropathy), an abnormal curvature of the spine (kyphoscoliosis), impaired muscle coordination (ataxia), and joint deformities (contractures).
    • Some have retinitis pigmentosa 
    • Females with PMM2-CDG have hypergonadotropic hypogonadism, which affects the production of hormones that direct sexual development. As a result, females with PMM2-CDG do not go through puberty. 


prevalence of CDG

More than 800 individuals with PMM2-CDG have been identified worldwide.


what happens in CDG?

 This gene provides instructions for making an enzyme called phosphomannomutase 2 (PMM2). The PMM2 enzyme is involved in a process called glycosylation, which attaches groups of sugar molecules (oligosaccharides) to proteins. Glycosylation modifies proteins so they can perform a wider variety of functions. Mutations in thePMM2 gene lead to the production of an abnormal PMM2 enzyme with reduced activity. Without a properly functioning PMM2 enzyme, glycosylation cannot proceed normally. As a result, incorrect oligosaccharides are produced and attached to proteins. The wide variety of signs and symptoms in PMM2-CDG are likely due to the production of abnormally glycosylated proteins in many organs and tissues.


what is kearns-sayre syndrome?

  • genetic condition that affects many parts of the body BUT SPECIALLY THE EYES
  • young people before 20 yo
  • progressive external ophthalmoplegia
  • ptosis
  • pigmentary retinopathy degeneration
  • cardiac blocks
  • ataxia
  • increased CSF proteins
  • muscle weakness
  • deafness
  • kidney problemsThe muscles have an excess of mitochondria
  • 1 in 100K individuals
  • mitochondrial inheritance


what is a CLIA lab?

Clinical Laboratory Improvement Amendments (CLIA) regulate laboratory testing and require clinical laboratories to be certificated by their state as well as the Center for Medicare and Medicaid Services (CMS) before they can accept human samples for diagnostic testing


what is LCA triad?

  1. decreased vision
  2. nystagmus
  3. flat ERG
  4. Paradoxical pupillary response (pupils do not constrict, or dilated and then constrict slowly)

others are oculo-digital reflex, pigmentary retinopathy, strabismus


LCA frequency

2-3 per 100,000


  1. How many LCA genes have been identified?
  2. which are the 3 most common genes?
  3. what percentage represent the rest of the genes?
  4. in what percentage of LCA patients the genes remains unknown?

  1. 14 genes
  2. RPE65, CEP290, CRB1, GUCY2D, CRX
  3. small %
  4. 30%


features of CRX mutation in LCA

The CRX gene provides instructions for making a protein called the cone-rod homeobox protein.

This protein is called a transcription factor.

In the retina, the cone-rod homeobox protein is necessary for the normal development of light-detecting cells called photoreceptors. 


RPE65 functions? where is it produced?

The RPE65 protein is involved in a multi-step process called the visual cycle, 

When light hits photosensitive pigments in the retina, it changes  11-cis retinal (a form of vitamin A) to

 all-trans retinal.

The RPE65 protein then helps convert all-trans retinal back to 11-cis retinal so the visual cycle can begin again.

its produced on the RPE.


what happens in the visual cycle?

When light hits photosensitive pigments in the retina, it changes  11-cis retinal (a form of vitamin A) to

 all-trans retinal.


The RPE65 protein then helps convert all-trans retinal back to 11-cis retinal so the visual cycle can begin again.


what is curcumin?

The plant turmeric (Curcuma longa) is very well known in India.

Traditionally, turmeric was used for nearly every health condition known - from smallpox to a sprained ankle.

This plant has a compund known as curcumin. Just as oranges are a source of vitamin C, turmeric is a source of curcumin. Today, we extract curcumin from turmeric to use as a natural medicine


what is cockayne syndrome?

RARE syndrome

  • microcephaly
  • failure to thrive
  • delayed development
  • photosensitivity
  • skin light sensitivity
  • hearing loss
  • vision loss
  • tooth decay
  • bone abnormalities
  • brain abnormalities
  • cold hands and feet


cockayne syndrome frequency?

2-3 per million


what are the mutation sin cockayne syndrome?

what is the inheritance3 pattern



Autosomal recessive


what is Joubert syndrome?


  • affects many parts of the body
  • brain abnormality "molar tooth
  • hypotonia
  • ataxia
  • delayed development


how many genes involved in Joubert syndrome?

which ones?

  • 10 genes
  • autosomal recessive


what is Trichothiodystrophy?

  • also called TTD
  • its a RARE
  • inherited condition that affects many parts of the body
  • brittle hair that is sparse and easily broken. Fragil hair that is few and easily broken
  • hair is lacking sulfur, an element that normally gives hair its strength.
  • delayed development, significant intellectual disability, and recurrent infections; severely affected individuals may survive only into infancy or early childhood.


what is septo-optic dysplasia?

  • is a disorder of early brain development
  • 3 classic features:
    • optic nerve hypoplasia
    • maldevelopment of midline of brain ( corpus callosum, which is a band of tissue that connects the two halves of the brain, and the septum pellucidum, which separates the fluid-filled spaces called ventricles in the brain)
    • pituitary hypoplasia
  • ​​if you see optic nerve hypoplasia get 2 consults
    • ​​neurology
    • ​endocrinology


frequency of SOD septo-optic dysplasia

1 in 10,000 newborns


whatis the cause of SOD septo optic dysplasia?

  • unknown
  • few genes have been identified but they only explain rare cases
  • no family history
  • its an SPORADIC disease


what is GAN (giant axonal neuropathy)?

  • its an inherited condition
  • caused by mutations in the GAN gene
  • this gene produces Gigaxonin (part of the ubiquitin-proteasome system, which is a process that identifies and gets rid of excess or damaged proteins within cells. In particular, gigaxonin plays a role in the breakdown of neurofilaments, which comprise the structural framework that establishes the size and shape of axons.)
  • The neurofilaments become densely packed in the giant axons of people with giant axonal neuropathy. These giant axons do not transmit signals properly and eventually deteriorate, resulting in the death of neurons. The loss of nerve cells leads to problems with walking and sensation in people with giant axonal neuropathy.


what is the inheritance and gene for GAN?

Autosomal recessive

GAN gene



what are the signs and symptoms of GAN?

  • Giant axonal neuropathy is an inherited condition characterized by abnormally large and dysfunctional axons called giant axons.

  •  Signs & symptoms of giant  begin in early childhood and get worse over time.

  •  first have problems with walking. Later they may lose sensation, strength, and reflexes in their limbs; experience difficulty coordinating movements (ataxia); and require wheelchair assistance. Visual problems may also occur. Many affected individuals have extremely kinky hair as compared to others in their family.

    As the disorder worsens and the central nervous system becomes involved, paralysis, seizures, and a gradual decline in mental function (dementia) can also occur. Most people with giant axonal neuropathy do not survive past their 30s.


what is DICER1 syndrome?

  • DICER1 syndrome is an inherited disorder that increases the risk of a variety of cancerous and noncancerous (benign) tumors,
  • most commonly  lungs, kidneys, ovaries, and thyroid
  •  Affected individuals can develop one or more types of tumors, and members of the same family can have different types.
  • However, the risk of tumor formation in individuals with DICER1 syndrome is only moderately increased compared with tumor risk in the general population; most individuals with genetic changes associated with this condition never develop tumors.
  •  most commonly develop pleuropulmonary blastoma, Cystic nephroma, and ovaries and thyroid