I especially want to express my deep appreciation to Dr. Bruno Chikly for his very kind permission in allowing us to use and reproduce information from his book Silent Waves Theory And Practice Of Lymph Drainage Therapy. His books and works have brought hope and much needed information to countless thousands throughout the world coping with lymphedema and lymphatic disorders.
Also, I want to acknowledge other sources of information.
I have included many entry articles from OMIM, Online Mendelian Inheritance in Man provided by Johns Hopkins University. As a person who has done extensive research and search, I have come to a great respect and admiration for their unending work in presenting top quality information to both professionals and lay people alike.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM
Much information has been gathered as well from Pub Med, a section of the National Library of Medicine. A special note of thanks is due them as well for their service to the public.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi
Another excellant source of medical information provided by the government is Medline Plus. This is a service of the U.S. National Library of Medicine and the National Institutes of Health
http://www.nlm.nih.gov/medlineplus/
Finally, we must also mention the National Organizations of Rare Disorders. They provide valuable and hard to find information on a vast compendium of rare and little understood diseases and conditions.
==============
Syndromes
Associated With Lymphatic Dysplasia
1- Aagenaes
(lymphedema-cholestasis) syndrome
2-
Distichiasis (lymphedema-distichiasis) syndrome
3-
Dahlberg (lymphedema-hypoparathyroidism syndrome)
5-
Gorham-Stout-Haferkamp syndrome
6-
Hennekam’s syndrome
7-
Klinefelter syndrome
8-
Klippel-Trenaunay syndrome
9-
Maffucci’s syndrome:
10-
Melkersson - Rosenthal - Miescher syndrome
11-
Noonan syndrome
12-
Trisomy 10
13-
Trisomy 13
14-
Trisomy 18
15-
Trisomy 21
16-
Trisomy 22
17-
Turner syndrome
18-
Von Recklinghausen’s fibromatosis
19-
Yellow nail syndrome
20-
Other syndromes associated with lymphatic dysplasia
------------------------
Aagenaes
(Lymphedema-cholestasis) syndrome
First
description:
Aagenaes and
associates (Norway), 1968.
OMIM
(Online Mendelian Inheritance in Man database) reference number:
214900
Synonyms:
Cholestasis-lymphedema-syndrome
(CHLS),
Lymphedema-cholestasis
syndrome (LCS or LCS1), Cholestasis Aagenaes, Cholestasis hereditary
Norwegian
type.
Genetics:
Chromosome 15q.
Autosomal recessive inheritance.
Localization:
About 2/3 of the cases reported
are in Norway.
Onset:
usually puberty.
Clinical
description:
1-
Hepatologic manifestations
Chronic
recurrent cholestasis (bile flow obstruction)
Postnatal
icterus (jaundice)
The
liver may be enlarged; intrahepatic obstructive liver disease and
capillary
hemangiomata may also occur. The disease may slowly evolve to hepatic
cirrhosis
and giant-cell hepatitis with fibrosis.
2-
Lymphologic manifestations
Lymphedema
develops during childhood as a result of lymphatic hypoplasia. This
occurs most
frequently in the lower extremities, but the condition infrequently
affects
upper extremities, and rarely the face or lungs.
------------------------
Distichiasis (a.k.a.
Lymphedema-Distichiasis) syndrom
First
description:
1954,
University of Houston, Texas.
OMIM
(Online Mendelian Inheritance in Man database) reference number:
153400
Genetics:
Chromosome 16q24.3.
Mutation of the gene FOXC2 (MFH1).
Onset:
usually at
puberty.
Clinical
description:
1-
Ophthalmologic manifestations
Distichiasis:
the double row of eyelashes may be difficult to identify clinically.
It
may be discovered because of an irritation of the cornea, corneal
abrasion or in
some cases corneal ulceration
Ptosis
of the eyelids
Photophobia.
Partial
ectropion (eversion of part of an eyelid) of
the lateral third of the eyelashes.
2-
Lymphologic manifestations
pterygium
colli (Webbing of the neck)
Primary
lymphedema, often appearing at puberty
Thoracic
duct abnormalities
Chylothorax
3.
Osteoarticular manifestations
Vertebral
segmentation abnormalities: irregularities of end plates, spinal
extradural
cysts, etc.
Amelogenesis
imperfecta (defective
dental enamel)
4.
Cardiologic manifestations
Congenital
heart disease, e.g. tetralogy of Fallot or atrioventricular block
Capillary
hemangiomata
D-
Other associated symptoms:
Cleft
palate
Low
hairline
------------------------
Dahlberg
(Lymphedema-Hypoparathyroidism) Syndrome
First
description:
Dahlberg
P.J.,
1983.
OMIM
(Online Mendelian Inheritance in Man database) reference number:
247410
Synonyms:
Dahlberg newcomer syndrome.
Genetics:
autosomal recessive and X-linked recessive type.
Clinical
description:
This
syndrome consists mainly of primary lymphopathy of extremities or
lungs,
progressive renal failure, mitral valve prolapse, brachydactyly (abnormal
shortness of toes or fingers) and hypoparathyroidism.
1-
Lymphologic manifestations
Primary
lymphedema of upper or lower extremities that can develop soon after
birth
Pulmonary
lymphangiectasia (dilatation
of lymph
vessels)
2-
Nephrologic manifestations
Progressive
renal failure that may require kidney transplantation
3-
Ophthalmologic manifestations
Cataracts
(bilateral)
Ptosis
Telecanthus (increased distance between the
inner aspect of the eyelids)
4-
Other associated Symptoms
Mitral
valve prolapse
Brachydactyly
(brachytelephalangy)
Hypoparathyroidism
Hypocalcemia
Hypothyroidism
Broad
nasal bridge and lateral displacement of the inner canthi.
Thick
skin
Increased
body hair
Short
stature/dwarfism
Fabry's
disease
First
description:
Independently described in 1898 by the dermatologist Jonathan Fabry
("purpura
haemorrhagica nodularis") and the surgeon William Anderson ("multiple
capillary angiectasis").
OMIM
(Online
Mendelian Inheritance in Man database) reference number:
301500
Synonyms:
Anderson-Fabry
Disease,
alpha - galactosidase A deficiency, angiokeratoma corporis diffusum
(universale),
cardiovasorenal syndrome, ceramide lactoside lipidosis, ceramide
trihexosidase
deficiency, GLA deficiency, glyosphingolipidosis, hereditary dystopic
lipidosis,
lactosyl ceramidosis, Ruiter-Pompen syndrome, Sweeley-Klionsky disease,
thesaurismosis hereditaria, thesaurismosis lipoidica, trihexosidase
deficiency
disease.
Genetics:
X-linked lysosomal disorder.
Defect
of the gene alpha-galactosidase
A (enzyme involved in the biodegradation of lipids) located on the long
arm of
the X chromosome (Xq22).
Some
cases of mutation are
likely.
Incidence:
1 case per 117, 000-40,000
Mortality/morbidity:
The average age at death is 41 years.
Sex:
Fabry’s disease most often affects hemizygous males, but is sometimes
found in
heterozygous females, who do not display as severe symptoms, or as
complete a
set.
Age
of
onset: Generally from
childhood to adolescence.
Clinical
description:
This disorder
leads to a progressive accumulation of globotriaosylceramide (Gb3) and
related
glycosphingolipids (GSLs) in vascular endothelial lysosomes of the
skin,
kidneys, heart, nervous system, and blood vessels.
1- Dermatologic
manifestations:
Cutaneous angiokeratoma: maculopapular skin lesions
consisting of reddish
to dark purple pin-head size spots (dilated capillaries). They could be
located
anywhere in the body but they are usually located in regions where skin
folds
and stretching occur.
Hypohidrosis, anhidrosis: decreased or absent sweating
Teleangiectasia (enlargement of small blood vessels)
Rash
2- Lymphologic
manifestation
Lymphedema in the lower extremities; the etiology is
unknown.
3-
Musculoskeletal manifestation
Acroparesthesia (crises of severe pain, burning, and/or
itching in the
extremities, associated with fever)
4-
Ophthalmologic manifestations
Corneal dystrophy
Corneal opacities
Cataracts
5-
Cardiovascular manifestations
Angina
Coronary artery disease
Myocardial ischemia
Congestive heart failure
Left ventricular hypertrophy
Mitral insufficiency
Mitral valve prolapse
Conduction abnormalities
6-
Neuropsychiatric manifestations
Stroke
Aneurysm
Seizures
Hemiplegia
Hemianesthesia (loss of sense of touch in the right or
left half of the
body)
Aphasia
Cerebral hemorrhage.
Psychotic behavior
7- Renal
manifestations
Chronic renal insufficiency
Kidney failure
8-
Gastrointestinal manifestations
Episodes of abdominal or flank pain, diarrhea,
or vomiting
Jejunal diverticula
Peritonitis
9- Endocrine
manifestations
Abnromal growth
Delayed onset of puberty.
10- Other
manifestations
Chronic bronchitis
Anemia
Gorham-Stout-Haferkamp
syndrome (lymphangiomatosis)
First
description:
1955, Gorham
and associates.
Synonyms:
Acro-osteolysis syndromes,
diffuse cystic angiomatosis of
bone, disseminated lymphangiomatosis, thoracic lymphangiomatosis,
Gorham-Stout
syndrome, Gorham's vanishing bone disease, Hajdu-Cheney syndrome,
idiopathic
massive osteolysis, idiopathic multicentric osteolysis, massive Gorham
osteolysis, phantom bone disease, osteolysis of Martorell, Trinquoste
syndrome.
Clinical
description:
Studies
of about 200 cases have been published in scientific literature.
Osteolysis
(bone loss) created by angiomatous tissue (abnormal blood or lymphatic
vessel
growth)
1-
Osteoarticular manifestations
Abnormal
vessel growth (angioma = “vessel tumor”) produces areas of osteolysis
which
may be associated with
pathological
fractures.
Almost
any part of the skeleton
can be affected
but it is most often found in the cranium (parietal area), upper jaw,
maxilla, zygoma and extremities.
2-
Lymphologic manifestations
Lymphodysplasia
(intraosseous lymphodysplasia or lymphovenous dysplasia)
3-
Visceral manifestations
Lymphangiomas
of the spleen, or liver, lungs, mediastinum.
Hennekam’s Syndrome
First
description:
1989,
Hennekam and associates.
OMIM
(Online Mendelian Inheritance in Man database) reference number:
235510
Synonym:
Intestinal
lymphangiectasia-lymphedema-mental retardation syndrome.
Genetics:
Autosomal
recessive inheritance.
Sex
ratio: Equal
sex ratio.
Clinical
description:
About
25 cases have been published in scientific literature.
1-
Lymphologic manifestations
-- mainly due to abnormal lymphangiogenesis
Lymphedema:
- Peripheral 100%
- Face: 86%
- Genital 71%
Lymphangiectasia
- Intestines 82%
- Lung 39%
- Heart 22%
- Other: kidneys, thyroid (rare)
2-
Facial features
Flat
face: 100%
Metopic
ridge: 31%
Craniostosis
(congenital ossification of cranial sutures)
Craniosynostosis
(premature ossification of cranial sutures)
Hypertelorism
(widely-spaced eyes)
Epicanthal
folds
Small
mouth
Small
ears
3-
Cardiovascular manifestations
Congenital
heart defects 20%
Blood
vessel abnormalities 40%
4-
Neuropsyc
Mental
retardation (inconsistent)
Seizures
Convulsions
5-
Other associated symptoms
Glaucoma
Dental
anomalies
Gingival
hypertrophy
Hearing
loss
Renal
anomalies
Syndactyly
(fusion of fingers or toes)
Klinefelter
Syndrome
First
descriptions:
1895
Richard Altmann, 1934 Walther Berblinger and 1942
Harry Fitch Klinefelter.
Synonyms:
Klinefelter-Reifenstein-Albright
syndrome, Reifenstein-Albright XXY syndrome,
aspermatogenesis-gynecomastia syndrome, chromosome XXY syndrome,
medullary
gonadal dysgenesis, primary microörchidism, puberal, seminiferous
tubule
failure, sclerosing tubular degeneration.
Genetics:
1-
47,XXY: approximately 80%-90%.
2-
Mosaic patterns: 46,XY/47,XXY, 46,XY/48,XXXY, and 47,XXY/48,XXXY:
approximately
10%.
2-
Structurally abnormal additional X: about 1%.
Incidence:
approximately 1 in 500-700 male births.
Sex
ratio: males
only.
Clinical
description:
1-
Endocrine manifestations
A-
Growth
Tall
stature
Usually
disproportionately long in upper and lower extremities (excessive
growth in the
long bones); the trunk is short in comparison
B-
Sexual characteristics
Male
hypogonadism (microörchidism - small testes), gynecomastia and
sterility (azoöspermia
or oligospermia)
Lack
secondary sexual characteristics (low androgen production):
Gynecomastia
(abnormally large breasts in a male) at late puberty
Testicular
dysgenesis: small and firm testicles with low sperm production.
(Penile
size is usually normal.)
Infertility/azoöspermia
may be present, caused by extensive hyalinization leading to atrophy of
the
seminiferous tubules.
2-
Neuropsychiatric manifestations:
A
majority of patients display some minor developmental and learning
disabilities.
Language
impairment
Behavioral
problems
Immaturity
Shyness
Lack
of common sense/judgment
Poor
self-esteem
Patients’
IQ score is reduced by about15 points for each additional X chromosome,
on
average.
3-
Cardiac and circulatory manifestations
Mitral
valve prolapse 55%
Varicose
veins 20-40%
4-
Odontologic manifestations
Taurodontism
(enlargement and deepening of the pulp chambers of the molar teeth):
40% of
patients.
Klippel-Trenaunay
(K-T) Syndrome and Kasabach-Merritt
syndrome
Synonyms:
Angio-osteohypertrophy syndrome, hyperoxemiating arterio-venous
angiomatosis
osteohypertrophy.
Genetics:
Gene may be located on 5q or p11.
Sex
ratio:
Females are
affected approximately twice as often as males.
Clinical
description:
K-T
can be characterized by a triad of symptoms (Gloviczki et al., 1991):
Hemangioma
(port-wine stain): 95%
Hypertrophy
of bones and soft tissues: 93% (limb hypertrophy: 67%)
Varicose
veins 76%
Approximately
65% of patients have all 3 symptoms (according to a Mayo Clinic study
of 252
patients, with
KTS between January 1956
and January 1995)
1-
Vascular manifestations
Vascular
dysplasia: port-wine stains, cavernous hemangioma, varicose veins,
arteriovenous
malformations, lymphedema and lymphangiomata.
A-
Hemangiomata
Port-wine
stain or "birthmark" (cutaneous capillary malformations) often in the
lateral aspect of the limb present with a well demarcated linear
border. These
cutaneous capillary malformations usually do not spontaneously regress
or
enlarge.
B-
Varicose veins and venous dysplasia
Venous
varicosities developed in 79% of cases (Muluk et al., 1995)
Typically
a large lateral superficial vein seen at birth.
Varicosities
may be quite extensive. Generally sparing the saphenous distribution,
they more
usually affect the popliteal or femoral veins, and sometimes both.
Associated
deep venous abnormalities can lead to serious complications, and may
include
aneurysmal dilatation, hypoplasia, aplasia and absent or incompetent
valves.
C-
Arteriovenous fistulae, the main feature distinguishing
Klippel-Trenaunay
syndrome from Parkes-Weber (see below), are rarely found in the
affected
extremity of K-T patients.
D-
Lymphodysplasia:
Lymphodysplasia
and resulting primary lymphedema of the extremities (most commonly the
legs) is
seen in K-T
These
can be either aplasia, dysplasia or hyperplasia
/ lymphangiectasia of the lymph vessels; they can be treated like any
other
primary lymphedema.
Lymphangioma
occurs in about 8% of these patients.
2-
Osteoarticular manifestations
Soft
tissue and bony hypertrophy
It
usually evolves during the first years of life and manifests commonly
in one
lower extremity or the other (71%). It occurs less frequently
bilaterally (20%)
or in the upper extremity (25%) [Gloviczki et al., 1991].
It
can lead to complications such as postural abnormalities or vertebral
scoliosis.
Differential
diagnosis:
It
is often difficult to distinguish between K-T syndrome and K-T-W or
Parkes Weber
syndrome. The absence of arteriovenous fistulae and the presence of
low-velocity
venous malformations inclines the physician to a diagnosis of
Klippel-Trenaunay
rather than Parkes Weber.
Complications
of K-T:
The
can include ulcerations, bleeding, cellulitis, deep vein thrombosis and
pulmonary embolism.
Involvement
of viscera (e.g. lungs, liver, kidneys or large intestine) can produce
specific
complications such as spontaneous rupture of hemangioma and internal
bleeding.
------------------------
Kasabach-Merritt
syndrome:
consumptive
coagulopathy:
The Kasabach-Merritt syndrome is a medical emergency in
K-T patients.
It involves
thrombocytopenia, caused
by the trapping of platelets in an
expanding
cavernous hemangioma, and occasionally excessive consumption
of clotting factors, resulting in
internal bleeding (e.g. in
Maffucci’s
syndrome
First
description:
Angelo Maffucci, 1881, Naples, Italy.
Synonyms:
Achondromatosis with hemangiomata, chondrodysplasia angiomatosis
syndrome,
chondrodystrophy and vascular hamartoma syndrome, chondrodystrophy with
angiomatosis, cutaneous dyschondroplasia-dyschromia syndrome,
dyschondroplasia-angiomatosis syndrome,
dyschondrodysplasia-haemangiomas
syndrome; Kast’s disease, Maffucci-Kast syndrome, multiple
enchondromatosis
syndrome.
Genetics:
inheritance unknown.
Sex
ratio: Both
sexes affected but males more frequently.
Clinical
description:
Benign
tumors of cartilage (enchondromas), associated with multiple cavernous
hemangiomata.
1-
Osteoarticular manifestations
Nodular
tumors usually develop before puberty and continue to evolve later.
They can
lead to fracture, unequal length of the extremities and disharmonious
segmental
hypertrophy of the body.
Dyschondroplasia
of the hands is common (89%) in Maffucci’s syndrome, but they can be
found in
almost any bone.
2-
Vascular manifestations
Hemangiomata
in the skin of the limbs and in the viscera: eyes, pharynx, tongue,
meninges,
and intestines.
Lymphangiomata
and lymphangiosarcomata
Phlebangiectasia
(venous dilatatons)
3-
Dermatologic manifestations
Vitiligo
Pigmented
nevi
Melkersson-Rosenthal or
Melkerson-Rosenthal-Miescher Syndrome
First
descriptions:
Lothar von Frankl-Hochwart in 1891. Described by Melkersson in 1928.
Rosenthal
described the plicated
tongue in 1931.
Synonyms:
Rosenthal's syndrome II, Melkersson-Rosenthal-Schuermann syndrome,
Rossolimo’s
syndrome, Miescher’s cheilitis, Melkersson’s syndrome.
Genetics:
May be related to chromosome 9 (9p11).
Autosomal
dominant inheritance with variable expressivity.
Sex
ratio: Affects
men and women equally.
Clinical
description:
1-
Classical manifestations
Chronic
edema of the lips (granulomatous edema, also called cheilitis
granulomatosa,
cheilitis glandularis, cheilitis granulomatosis, essential
granulomatous
macrocheilitis) and other part of the face (chin, eyelids)
Peripheral
recurrent facial paralysis
Hypertrophic
plicated tongue (lingua plicata, “scrotal tongue”)
2-
Other manifestations:
Mild
lymphatic hyperplasia (usually with very little fibrosis)
Headaches
/ migraines
Ptosis
of the eyelids
Optic
neuritis.
------------------------
Noonan Syndrome (NS)
First
descriptions:
First reported by Kolinski in 1883. In 1930 Ullrich described this
disorder,
followed by Henry Turner 8 years later.
In
1971 this syndrome was completely described by Jacqueline Noonan, MD,
Professor of Pediatrics
in Kentucky, and
the syndrome was officially named “Noonan syndrome”.
OMIM
(Online Mendelian Inheritance in Man database) reference number:
163950
Synonyms:
Male Turner syndrome, female pseudo-Turner syndrome, pseudo
Ullrich-Turner
syndrome, Turner's phenotype with normal karotype, Ullrich-Noonan
syndrome, XX
Turner phenotype syndrome.
Genetics:
Autosomal dominant disorder with variable expression.
In
33-50% of cases Noonan syndrome is caused by a mutation of the gene
PTPN11
(which encodes the protein tyrosine phosphatase SHP-2) located on
chromosome 12
(12q 24).
Sex
ratio: Both
sexes are affected equally
Incidence:
approximately 1 in 1,000 to 2,500 births.
Clinical
description:
Noonan
syndrome (NS) is clinically similar to Turner syndrome but with a
normal number
of chromosomes.
1.
Craniofacial manifestations
Triangular
face
Down-slanting
upper eyelids (95%)
Thickened
helix (90%)
Low
posterior hairline (55%)
High
arched palate (45%),
Micrognathia
(small jaw) in 25%,
Low-set,
posteriorly-rotated ears
Hypertelorism
(widely-spaced eyes)
Webbed
neck (pterygium colli)
2.
Endocrine manifestations:
Growth
retardation
Short
stature or dwarfism
Sexual
development:
A. Males
Cryptorchidism (undescended testicles) (60%)
Small testes.
B. Females
Normal fertility
3.
Musculoskeletal manifestations
Cubitus
valgus (50%)
Superior
pectus carinatum (90-95%) (“pigeon breast”)
Inferior
pectus excavatum (concave chest, “funnel breast”)
Vertebral/sternal
anomalies
low-set
widespaced nipples
Dental
malocclusion (35%)
Short
curved fingers with blunt fingertips (30%),
Scoliosis
(10%)
Joint
hyperextensibility and hypotony
4.
Cardiovascular manifestations
Pulmonary
valve stenosis (50%)
Hypertrophic
cardiomyopathy (20-30%)
Atrial
septal defects (10-20%)
Asymmetric
septal hypertrophy (10%)
Ventral
septal defects (5-15%)
Persistent
ductus arteriosus (3%).
Tetralogy
of Fallot
5.
Lymphologic manifestations (20%)
Distal
chronic lymphedema of dorsal surface of the feet. This can be the first
clinical
symptom of NS.
Genital
lymphedema
Intestinal
lymphangiectasia
Pulmonary
lymphangiectasia
Cervical
cystic hygroma (benign lymphatic tumors of the neck)
Hydrops
fetalis (fetal edema)
6.
Neurobehavioral manifestations
Mild-moderate
mental retardation (33%)
Gross
motor developmental delay (25%)
Speech
and language developmental delay (20-30%)
Verbal
performance discrepancy (15%)
Seizures
(13%)
7.
Hematologic manifestations
Coagulation
defects (33%)
- Partial deficiency of factor XI:C, XII:C, and VIII:C
- Thrombocytopenia
- Von Willebrand disease
Splenomegaly
(50%)
Hepatosplenomegaly
(25%)
8.
Ophthalmologic manifestations
Strabismus
(about 55%)
Myopia
Amblyopia
Nystagmus.
9.
Dermatologic manifestations
Large
finger pads (67%)
Neurofibromatosis.
10.
Otologic manifestations
Mild
hearing loss or deafness (12%)
------------------------
trisomy
10
Genetics:
presence of an additional chromosome 10.
Incidence:
1.8% of all spontaneous abortions
Clinical
description:
All
cases of trisomy 10 are mosaic, i.e., the defect is not present in all
cells.
Babies born live with the condition have usually a very
short life
expectancy.
Clinical
manifestations include: mental and growth retardation, cryptorchidism
(undescended
testicles), hypertelorism (increased distance between the eyes), marked
plantar
and palmar furrows and congenital heart defects.
------------------------
Trisomy
13
First
described by:
Klaus Patau, 1960.
Synonyms:
Chromosome 13 trisomy syndrome, trisomy 13, Patau syndrome
Bartholin-Patau
syndrome, trisomy 13-15, trisomy D.
Genetics:
presence of an additional chromosome 13.
Incidence:
approximately 1 in 4,000-10,000 birth.
Mosaic
trisomy 13 about 5% of cases.
Clinical
description:
Most
usually do not survive the first 3-6 months of life.
Severe
mental retardation is common
Holoprosencephaly
(forebrain defect), sloping forehead
Microcephaly
Wide
sagittal suture and fontanelles
Cleft
lip/palate
Cardiac
defects (atrial or ventricular septal defects, dextroposition of the
heart)
Kidneys
defects (hydronephrosis, hydroureter)
Polydactyly;
clinodactyly (condition in which the little finger is curved toward the
ring
finger)
Hypertelorism
Deformed
ears
Single
umbilical artery
Deafness
------------------------
Trisomy
18
First
description:
John Edwards, 1960.
Synonyms:
Edwards syndrome, trisomy E,
trisomy 16-18.
Genetics:
Presence of an additional 18th chromosome.
In
95% of the cases it is a pure trisomy, in 3% it is mosaic and 2% of
translocations. (rearrangements of chromosomal material.)
Incidence:
Approximately 1 in 3,000-8,000 births.
About
ninety percent of these patients do not survive the first year.
Clinical
description:
1.
Craniofacial manifestations
Microcephaly
Low
set malformed ears
Micrognathia
(small jaw)
Hypertelorism
Cleft
lip/palate
Webbed
neck
Cystic
hygroma or nuchal edema/thickening
Choroid
plexus cysts
Large
cisterna magna (increased intracranial space outside the posterior
brain)
Cerebellar
hypoplasia
Seizures
2.
Other manifestations
Cardiac
abnormalities (90%): ventricular septal defect, trial septal defect,
patent
ductus arteriosus
Lung
abnormalities
Kidney
and ureter abnormalities
Hypertension
Spina
bifida
Scoliosis
Eye
abnormalites
Hearing
loss
Omphalocele (herniation of abdominal contents in the umbilical area)
Trisomy 21
(Down syndrome)
First
descriptions:
1838, Jean
Etienne Esquirol. John Down, 1866.
Synonyms:
Trisomy 21, mongolism, congenital acromicria syndrome. mongoloid
idiocy,
mongolism, trisomy G, Langdon-Down syndrome, Langdon Down disease,
morbus Down.
Genetics:
presence of an
additional chromosome 21.
Incidence:
approximately 1 in 700 births.
Risk
increases with the age of the mother.
Clinical
description:
1.
Craniofacial and neurologic manifestations
Mental
retardation is present almost 100 % of the time in these individuals,
ranging
from very mild to severe
Microcephaly,
short head
Sloping
forehead
Flat
nasal bridge, flattened nose
Protruding,
enlarged, fissured tongue
Upward
slanting eyes
Epicanthal
fold (rounded fold of skin at the inner corners of the eyes)
Low-set
ears
Small
ear canals
Short
neck
Nuchal
edema/thickening
Webbed
neck
2.
Musculoskeletal manifestations
Hands:
- Short and broad hands with short fingers
- abnormal palmar creases (“simian crease”)
- shortening of the middle phalanx of the fifth digit
resulting in
clinodactyly
Atlanto-axial
subluxation
3.
Cardiologic manifestations
Occurrence:
in 50% to 85% of Down syndrome individuals.
Endocardial
cushion abnormalities, ventricular septal defects, mitral valve
abnormalities.
4.
Gastrointestinal manifestations
Esophageal
atresia (obstruction of the esophagus)
Duodenal
atresia (obstruction of the duodenum)
Anorectal
malformations (imperforate anus)
Hirschsprung’s
disease
5.
Nephrologic manifestations
Renal
pyelectasis (dilation of the renal pelvis) (25%)
6.
Other manifestations
Premature
aging,
Alzheimer’s
disease
Acute
myeloid leukemia.
Delayed
puberty, early menopause
Hypotonia
Lymphedema
Cystic
hygroma
Omphalocele
Hydrothorax
Imperforate
anus
Short
umbilical cord
Short
stature
------------------------
Trisomy
22
Synonyms
and related Syndromes: Cat Eye, Cayler cardiofacial syndrome,
charge
association, DiGeorge syndrome, Shprintzen syndrome, velocardiofacial
syndrome.
Genetics:
presence of an additional chromosome 22.
Deletion
usually affects chromosome 22q11.
Incidence:
3-5% of all spontaneous
abortions.
Clinical
description:
1.
Craniofacial and neurologic manifestations:
Microcephaly
Long
fingers
Hypertelorism
Low
set ears
Cleft
palate/lip
Flat
nasal bridge
Epicanthal
folds
Nuchal
edema/thickening
Webbed
neck
Facial
edema
Mental
retardation
2.
Other manifestations
Growth
retardation
Hypotonia
Cardiac
abnormalities
Kidney
abnormalities
Gastrointestinal
abnormalities
Anal
stenosis
Seizures
Hearing
loss
------------------------
Turner
Syndrome
First
descriptions:
Giovanni
Morgagni, 1768. Henry Turner, 1938.
Synonyms:
Monosomy X, Turner-Varny Syndrome; Bonnevie-Ulrich syndrome;
Morgagni-Turner-Albright syndrome, chromosome XO syndrome, genital
dwarfism,
gonadal dysgenesis (45,X); ovarian dwarfism, ovarian aplasia,
pterygolymphangiectasia; Schereshevkii-Turner syndrome.
Genetics:
absence (total or partial) or alteration of X chromosome (Xp11.2-p22.1).
Possible
chromosomal anomalies:
-
45, XO karyotype: 55%.
-
46, XX karyotype: 25% with defective X chromosomes (deletion,
duplication etc.).
-
Mosaics: 15%.
Incidence: