Chromosome 13

1.) Patau Syndrome

I. Karyotype Description
Trisomy 13, also called Patau syndrome, is a chromosomal condition associated with severe
intellectual disability and physical abnormalities in many parts of the body. Individuals with trisomy 13
often have heart defects, brain or spinal cord abnormalities, very small or poorly developed eyes
(microphthalmia), extra fingers or toes, an opening in the lip (a cleft lip) with or without an opening in
the roof of the mouth (a cleft palate), and weak muscle tone (hypotonia). Due to the presence of several
life-threatening medical problems, many infants with trisomy 13 die within their first days or weeks of
life. Only five percent to 10 percent of children with this condition live past their first year.
II. Key Clinical Features
Many of the clinical features widely vary; however, severe mental deficiency is a consistent feature
in children born with Patau syndrome.
Holoprosencephaly
Polydactyly
Flexion of the fingers
Rocker-bottom feet
Facial clefting
Neural tube defects, and heart defects are also frequent clinical features.
Patau syndrome is generally recognized at birth by the presence of structural birth defects and poor
neurologic performance.
III. Diagnostic test
Chromosomal microarray
Principle:
Chromosomal microarray (CMA) testing looks for extra (duplicated) or missing
(deleted) chromosomal segments, sometimes called copy number variants (CNVs).
These include:
Microdeletions and microduplications of chromosome segments, which are too small
to see under a microscope but may contain multiple genes.
Most abnormalities of chromosome number (trisomy, monosomy, etc.), including
Down syndrome
Most unbalanced rearrangements of chromosome structure (translocations, etc.)

Result:
Microarray refers to a microchip-based testing platform that allows high-volume,
automated analysis of many pieces of DNA at once. CMA chips use labels or probes that
bond to specific chromosome regions. Computer analysis is used to compare a patients
genetic material to that of a reference sample. A difference between a patients DNA
and the reference sample is called a variant.
Reference:
https://ghr.nlm.nih.gov/condition/trisomy-13

2.) Chromosome 13, Partial Monosomy 13q

I. Karyotype Description
Partial Monosomy 13q is a rare chromosomal disorder in which a portion of the long arm (q) of
chromosome 13 is missing (deleted or monosomic). The range and severity of symptoms may vary
greatly, depending upon the exact size and location of the deletion on 13q.
II. Key Clinical Features
Low birth weight and may fail to grow at the expected rate (failure to thrive).
Short stature.
Psychomotor retardation
Severe intellectual impairment
Unusually small head (microcephaly), a wide, flat nasal bridge, a small lower jaw
(micrognathia) with an abnormally prominent upper jaw (maxilla), protruding front
teeth (incisors), large, low-set ears; and/or a short neck with abnormal skin folds
(webbing).
III. Chromosomal and/or Molecular Diagnostic Tests
1. FISH TEST
Principle:
Fluorescent in situ hybridization; a technique used to identify the presence of
specific chromosomes or chromosome regions through hybridization (attachment) of
fluorescently labeled DNA probes to denatured chromosomal DNA. Examination under
fluorescent lighting detects the presence of the hybridized fluorescent signal (and hence
presence of the chromosome material) or absence of the hybridized fluorescent signal
(and hence absence of the chromosome material).
Result:
With interphase FISH, probes are introduced directly to the interphase cell.
Interphase FISH is often used for rapid detection of specific types of aneuploidy in fetal
cells and for the detection of certain deletions, duplications, and other abnormalities in
tumor cells. In contrast to metaphase FISH, interphase FISH does not permit
visualization of the actual chromosomes; therefore, certain structural rearrangements
or aneuploidy will not be detected.
With metaphase FISH, cells progress through the division process until metaphase,
when chromosomes are condensed and can be individually distinguished. In contrast to
interphase FISH, metaphase FISH permits visualization of the actual chromosomes as
well as the general location of the abnormality on the chromosome.
2.Chromosomal microarray
Principle:
Chromosomal microarray (CMA) testing looks for extra (duplicated) or missing
(deleted) chromosomal segments, sometimes called copy number variants (CNVs).
These include:
 Microdeletions and microduplications of chromosome segments, which are too small
to see under a microscope but may contain multiple genes.
Most abnormalities of chromosome number (trisomy, monosomy, etc.), including
Down syndrome
Most unbalanced rearrangements of chromosome structure (translocations, etc.)

Result:
Microarray refers to a microchip-based testing platform that allows high-volume,
automated analysis of many pieces of DNA at once. CMA chips use labels or probes that
bond to specific chromosome regions. Computer analysis is used to compare a patients
genetic material to that of a reference sample. A difference between a patients DNA
and the reference sample is called a variant.

Reference:
https://rarediseases.org/rare-diseases/chromosome-13-partial-monosomy-13q/

Chromosome 14 Abnormality
1.) FOXG1-related disorder
I. Karyotype description
FOXG1 syndrome is a condition characterized by impaired development and
structural brain abnormalities. Affected infants are small at birth, and their heads grow
more slowly than normal, leading to an unusually small head size (microcephaly) by
early childhood. The condition is associated with a particular pattern of brain
malformations that includes a thin or underdeveloped connection between the right
and left halves of the brain (a structure called the corpus callosum), reduced folds and
grooves (gyri) on the surface of the brain, and a smaller than usual amount of brain
tissue known as white matter.
II. Key clinical features
Dysmorphic features and Rett-like clinical course
Normal perinatal period,
Postnatal microcephaly
Seizures
Severe mental retardation.
III. Chromosomal and/or Molecular diagnostic tests
Detection of homozygosity
Principle:
Simulate 120 Mb of sequence data in order to know the true state of
autozygosity. Then extracted common variants from this sequence to mimic the
properties of SNP platforms and performed ROH analyses using three popular ROH
detection programs, PLINK, GERMLINE, and BEAGLE. Varied detection thresholds for
each program (e.g., prior probabilities, lengths of ROHs) to understand their effects on
detecting known autozygosity.
 Result: Within the optimal thresholds for each program, PLINK outperformed GERMLINE and
BEAGLE in detecting autozygosity from distant common ancestors. PLINK's sliding window
algorithm worked best when using SNP data pruned for linkage disequilibrium (LD).
References:
https://www.ncbi.nlm.nih.gov/gtr/conditions/C3150705/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188534/
https://ghr.nlm.nih.gov/condition/foxg1-syndrome#diagnosis

2.) Ring chromosome 14 syndrome

I. Karyotype Description
Ring chromosome 14 syndrome is a condition characterized by seizures and intellectual
disability. Recurrent seizures (epilepsy) develop in infancy or early childhood. In many cases,
the seizures are resistant to treatment with anti-epileptic drugs. Most people with ring
chromosome 14 syndrome also have some degree of intellectual disability or learning
problems. Development may be delayed, particularly the development of speech and of
motor skills such as sitting, standing, and walking.

II. Clinical Features

Delayed psychomotor development with mental retardation and poor speech.
Dysmorphic features, including broad, flat nose, synophrys, narrow palpebral fissures, high-
arched palate, and cubitus valgus.
Microcrania and poorly mineralized long bones and bones of the hand.

III. Chromosomal and/or Molecular Diagnostic Tests

The diagnosis of r(14) syndrome can be so far achieved only through cytogenetic tests:
currently no clinical, biochemical, electrophysiological and neuro-radiological data have
been found to be specific nor determinant for the diagnosis.
Reference:
https://ojrd.biomedcentral.com/articles/10.1186/s13023-017-0606-4
https://omim.org/entry/616606