Genetic Syndromes Affecting Movements

 Genetic syndrome: Causes dysmorphic features,

developmental delay, cognitive impairment, mental
retardation
 More research on down syndrome while
others( several) still require attention/research
 why do we (PT’s) need to study this????
 Dysmorphology and Common clinical Malformation
 Dysmorphology cont..
 Dysmorphology: Study of  Disruption: abnormal
atypical anatomic development breakdown of tissue in the
 Malformation: is a structural normal fetus causing an
defect in an organ or body ( cleft anatomical defect of an organ.
lip, polydactlyly)  Syndrome: pattern of
 Dysplasia: an abnormal multiple malformations due to a
organization of cells into tissues single cause ( genetic or
and the structural consequences ( environmental)
limb defects)
 Deformation: alteration in the
form, shape, or position of a
normally formed body part by
mechanical forces ( internal tibial
torsion)
 Normal Gene structure and function
some important terms
 DNA: contains genetic information
(1-2% actually encodes protein) used
in development and functioning.
 Chromosome: Single, very long DNA
helix on which thousands of genes are
encoded.
 46 chromosomes ( 23 pairs) homologs
(22pairs), 22 pairs are autosome while
1 pair is sex chromosome
 Cytogenetics: study of chromosome
 Karyotype: picture or display of
chromosome according to length (
46,XX/46,XY)
 Gene: length of DNA that codes for
specific proteins ( 30,000 genes in human)
 Locus: a gene’s specific location
on a chromosome
 Alleles: Different DNA sequence
for a particular gene ( or a copy of
gene on chromosome)
 Homozygous: same allele on
both pairs
 Heterozygous: Different alleles on
both pairs
 Genotype: Individual alleles and
precise genetic make-up at a specific
locus
 Phenotype: physical or physiological
manifestation of the genotype
 Mutation
 Alteration in the DNA sequence of gene
 Can cause genetic variation and genetic disorder
 Causes: naturally occurring, radiation, viruses, Mutagenic chemicals
( carcinogens, smoke particles)
 Rate of mutation varies with size of gene and paternal or maternal
age
DNA has its own repair mechanism, disorder occurs when repair
mechanism is dysfunctional.
 Genetics and Development.?????
o Genes--- Genetic mediators( growth factors/ paracrine molecule & their receptors, DNA
transcription factor, extracellular protein- collagens, fibrillins, elastin ) --- development of
body structure
Example of Genotype, Phenotype, and Mutation
(Punnett square for petal color in pea)
 Chromosomal Disorders
 Alteration in number(46) or structure
 Chromosome Number Abnormalities
• Polyploidy ( Presence of extra copy of chromosome)
• Polyploidy:Diploid-46 (normal)
• Polyploidy: triploid-69,tetraploid-92 ( aborted,lethal)
• Aneuploidy: absence or duplication of a chromosome in a cell
 Structural chromosomal disorders:
• Deletion, inversion, translocation, duplication, etc
Chromosomal deletion/duplication
Chromosome inversion/Translocation
 Chromosomal disorders
 Most prominent features
are development delay and
cognitive impairment?????
 Autosomal trisomy: due to
advanced maternal age
 Down Syndrome: (Trisomy 21)
 Female Karyotype: 47,XX+21
 Musculoskeletal Features:
Joint hypermobility, atlanto-
axial instability, wide gape
between toe 1 &2 , low tone
especially abdominals
 Trisomy cont…
 Trisomy 18 ( Edwards Syndrome)
 Majority of fetus results in spontaneous abortion. 90% dies
within one year
 More than 100 typical malformation usually involves CVS, GIT,
urogenital, and skeletal, and hypertonia
 Flexion contractures of fingers which are overlapping,
 Trisomy 13 ( patau syndrome):
 90 % conception are lost, 5 % survive less than 5 months)
 Microcephaly, deafness, cleft lip, post axial polydactyly,
cognitive impairment.
Polydactyly, cleft lip.
 Sex Chromosome Aneuploidy
 Inactivation of X chromosome
 Turner syndrome (monosomy 23)
Missing one X chromosome in
female(45, X)
 Features: short stature, wide
neck, broad trunk, heart
defect,infertility, osteoporosis
due to estrogen deficiency.
 : presence of an extra
chromosome in Kleinfelter
syndrome in male(47, XXY)
 Features: Gynescomastia,
increased stature, learning
disability
 Chromosome Deletions
 Cri-du-chat syndrome: due to
loss of part of short arm of
chromosome (p), 46,XX, del[5p]
 Features: Cat like cry, low birth
Weight, hypotonia, microcephaly,
macrostomia, hypertelorism,
epicanthal folds, strabismus, a
broad nasal ridge, clumsiness,
and hyperactivity with repetitive
movements, learning disability,
cystic fibrosis, self-injurious
behavior.
Cat Cry syndrome
 Chromosome Deletions Cont..
 Wolf-Hirschhorn syndrome  Angelman syndrome
 46,XX,del[4p] syndrome:
 Feature: Craniofacial anomalies,  del[15q]
occular malformation, cleft
lip/palate, CHD, growth  Maternal transmission
retardation, microcephaly.

 Feature: learning
Prader-Willi syndrome:
 del[15q]
difficulties, ataxia with jerky
 Paternal transmission
movements, puppet like
 Feature: Respiratory feeding gait, delayed milestones,
difficulties, hypotonia, delayed frequent/inappropriate
milestones, short stature, laughter.
 X-linked Disorder
 Few genes are located on Y chromosome, so majority of the x-
linked disorder are associated with X-chromosome
 X-linked recessive disorder ( both chromosomes are defective)
 Example: DMD occurs due to mutation in dystrophin gene
 Hemophilia A: mutation in the gene that determine blood
clotting factors VIII. (chromosomal Inversion)
X-linked dominant ( one defective chromosome)
 Fragile X syndrome:
 Features: cognitive impairment, hypotonia, joint hypermobility,
delayed motor milestones, large ears, elongated face,
prominent mandible.
Prominent features of fragile X Syndrome
Inheritance pattern for Hemophilia when
mother/father is a carrier
 Future of Research and Treatment
 Financial/ technological barriers:
 The majority of genetic disorder’s conceptions result in
spontaneous abortion ( natural remedy)
 Genetic Counseling:
 By checking family medical histories and taking blood samples
(for chromosome counts and tests for recessive traits)
 A genetic counselor can make a fairly accurate prediction
about the possibility of a couple having a child with a genetic
disease.
Genetic engineering: An artificial repair mechanism -very
expansive