There are many, rare syndromes associated with lymphatic dysplasia where in the patient will present with lymphedema. Therefore it is useful to include them in the website.
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.
1- Aagenaes (lymphedema-cholestasis) syndrome
2- Distichiasis (lymphedema-distichiasis) syndrome
3- Dahlberg (lymphedema-hypoparathyroidism syndrome)
5- Gorham-Stout-Haferkamp syndrome
8- Klippel Trenaunay Weber 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
20- Other syndromes associated with lymphatic dysplasia
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 is defined as a double row of eyelashes (from the Greek distichia, meaning double line).
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
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
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
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.
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
Lymphedema:
Lymphangiectasia
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- Neuropsychiatric manifestations:
Mental retardation (inconsistent)
Seizures
Convulsions
5- Other associated symptoms
Glaucoma
Dental anomalies
Gingival hypertrophy
Hearing loss
Renal anomalies
Syndactyly (fusion of fingers or toes)
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.
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.
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 internal organs, the head and neck area, or the extremities).
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
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.
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%)
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%)
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.
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
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)
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:
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
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
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: approximately 1 in 2,500 births.
Over 95% of fetuses abort spontaneously.
This syndrome is responsible for about 10% of all spontaneous abortions
Sex ratio: Females only.
Clinical description:
1. Lymphologic manifestations
The etiology of this syndrome is probably anomalies of lymphatic development that lead to lymphatic hypoplasia and valvular dysplasia. The mechanism may involve a deficiency in the gene responsible for activating the protein tyrosine kinase.
The most common manifestations are:
Pterygium colli (webbed neck), 50%
Cystic hygroma, a.k hydrops fetalis
Primary lymphedema of the dorsum of the hands and feet (80%)
Many of the associated lesions typically resolve spontaneously in adulthood.
2. Craniofacial and neurological manifestations
Triangular face
Midfacial hypoplasia
Micrognathia,
Low posterior hairline (80%)
Small lower jaw (70%)
Unusual shape and rotation of ears (80%)
Inner canthal folds (70%)
Eyelid ptosis
Shield chest with widely spaced nipples (78%)
Hearing loss (50%)
High palate (82%)
3. Cardiovascular manifestations
Congenital heart malformations (20-30%)
Coarctation of the aorta (15-30%)
Bicuspid aortic valve (33%)
Aortic aneurysms
Mitral valve prolapse (25%)
Ectopia cordis (malposition of the heart; in the most common form, the heart protrudes out of the chest through a split sternum)
Hypoplastic left heart
Pulmonary stenosis
Vascular malformations: vascular dysplasia, hemangiomata, venous ectasia,
multiple renal arteries (90%)
Hypertension
4. Dermatologic manifestations
Pigmented nevi (50-70%)
Vitiligo
Keloid(s)
Alopecia
Nail hypoplasia, soft upturned nails (70%)
Hirsutism
5. Ophthalmologic manifestations
Blepharoptosis (eyelid ptosis)
Strabismus
Cataracts
Nystagmus
Amblyopia
Myopia
6. Genitourinary manifestations
Double collecting system, absent kidney or abnormalities of the ureters (20%)
Kidney malrotation (15%)
Horseshoe kidneys (10%)
Unilateral aplasia or hypoplasia of the kidneys
7. Endocrinologic manifestations
Short Stature 100%
Gonadal dysgenesis or failure
Ovarian failure (90%)
Hypothyroidism (20-30%)
Type II diabetes (5%)
8. Musculoskeletal manifestations
Broad chest (80%)
Cubitus valgus (70%)
Short 4th metacarpals (50%)
Osteoporosis
9. Gastrointestinal manifestations
Protein-losing enteropathy
Hemangiomata
Intestinal bleeding
First descriptions: Giovanni Morgagni in 1768. F. Von Recklinghausen,1882.
Synonyms: Recklinghausen's phakomatosis, Recklinhausen neurofibromatosis, von Recklinghausen neuropathy, neurinofibrolipomatosis, neurinomatosis centralis et peripherica, neurofibromatosis generalisata, Elephant Man’s syndrome.
Genetics: autosomal dominant disorder with complete penetrance and highly variable expression, probably of neural crest origin. About 50% of all cases are in fact mutations.
Incidence: 1 per 3,000-3,500 births.
Clinical description:
1- Dermatologic manifestations
Café au lait spots spots(90-100%), made of increased or brownish skin pigmentation, commonly present in the trunk, axillae (axillary freckles), and inguinal area (inguinal freckles).
2- Neurobehavioral manifestations
Schwannomas or neurofibromata: multiple, often soft, sessile peripheral nerve tumors. These two types of tumor can become malignant over time.
Seizures
Hydrocephalus
Macroencephaly
Learning disabilities (25-60%).
Speech impediments
Mental retardation
3. Ophthalmologic manifestations
Lisch nodules (iris hamartomas or iris nevi) are clear, yellow or brown dome-shaped elevations on the surface of the iris (50% of adults).
They usually do not produce any ophthalmologic complications.
Optic nerve gliomas (15%) commonly located on the chiasm or pre-chiasm area.
They may provoke visual disturbances which do not usually progress to visual loss.
Proptosis (droopy eyelid)
Phakoma
Glaucoma
Corneal opacity
4. Endocrinologic manifestations
Short stature (43%)
Early or delayed puberty
Thyroid problems
5. Musculoskeletal manifestations
Scoliosis (10-20%)
Pseudoarthrosis (1-2%)
Kyphosis
Spinal dislocation
6. Other manifestations:
Lymphodysplasia
Hearing loss
Hypertension
Headaches
Malignancies: malignant myeloid disorders, neurofibrosarcomas, astrocytomas, meningiomas, medulloblastomas,
First description: P.D Samman and W.F.White, 1964.
OMIM (Online Mendelian Inheritance in Man database) reference number: 153300
Genetics: Autosomal dominant disorder. Mutation of the gene FOXC2 (MFH1).
Incidence: Rare – about 100 cases throughout the world have been described in the literature.
Approximately 10% of the cases are congenital.
Median age of onset: 40 year old.
Sex ratio: Twice as many female as males.
Clinical description:
The probable etiology of this syndrome is anomalies of lymphangiogenesis leading to lymphatic hypoplasia
The yellow nail syndrome is characterized by a triad of manifestations:
- Yellow nails (89%)
- Lymphedema (80%)
Pleuropulmonary symptoms (63%)
Chronic sinusitis or bronchiectasis.
1. Dermatologic manifestations
Thick, slow growing and dystrophic yellow or greenish nails
Onycholysis (a common nail disorder characterized by a spontaneous separation of the nail plate starting at the distal margin and progressing proximally)
Loss of the nail cuticle
2. Lymphologic manifestations
Symmetrical hypoplastic lymphedema, usually of the lower extremities; less frequently it can involve the upper extremities, face or genitalia.
Chylothorax
3. Pneumologic manifestations
Recurrent unilateral or bilateral pleuropulmonary effusion, bronchiectasia (usually the latest symptom to develop in the triad)
Chronic maxillary sinusitis
(short stature, hypertelorism, and abnormal scrotum). Probably X-linked recessive disorder.
See: Aarskog syndrome
or N-Acetyl-Alpha-D-Galactosaminidase deficiency (NAGA).
These syndromes may lead to progressive neurologic abnormalities (psychomotor retardation). Gene location: 22q11.
(Carbohydrate-Deficient Glycoprotein syndrome Type Ib; Gastrointestinal type Mannosephosphate Isomerase deficiency). The clinical features include: severe psychomotor retardation and blood coagulation abnormalities (Jaeken et al. 1980)
Gene location: 15q22-qter.
German syndrome: arthrologic disorders, hypotonia-hypokinesia, and lymphedema (German J. et al., 1975).
Gene location: 20q13.33
(generalized edema of the fetus of non immunologic origin)
Also called “familial idiopathic dysproteinemia” (Homburger and Petermann, 1949). Patients with intestinal lymphangiectasia may have lower extremities lymphedema, vascular changes, hypogammaglobulinemia, lymphocytopenia, and skin anergy
(lissencephaly is characterized by microcephaly and a thickened cortex), Norman-Roberts Type. Gene location: 7q22.
Facial Changes
(Cumming, W. A.; 1986).
Campomelia is characterized by an abnormal curvature of the long bones, especially from lower extremities.
Gene location: 16q24.3.
See: Lymphedema-Ptosis
See: Dysplasia-Anhidrotic-Immunodeficiency or OL-EDA-ID syndrome (Duffinger et al. 2001).
Gene location: Xq28.
(Franck J., Pipper P.G., 1959)
The patients affected by Nevo syndrome may have kyphosis, increased growth, volar edema, spindle-shaped fingers, hyperbilirubinemia, and generalized hypotonia (Nevo S. et al., 1974)
Peho Syndrome is progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (Salonen R. et al, 1991)
Include: Prolidase deficiency, prolidase, imidodipeptidase, proline peptidase d deficiencies, dipeptidase and aminoacyl-l-proline hydrolase,.
Patient with PEPD may have dermatologic manifestations (particularly leg ulcers) and mental retardation.
Gene location: 19cen-q13.11
Pateints are female that do not develop secondary sexual characteristics at puberty and present streak gonads.
Gene location: Xp22.11-p21.2.
see also: Swyer syndrome
(Published with permission from the author of Silent Waves Theory And Practice Of Lymph Drainage Therapy (Ldt) With Applications For Lymphedema, Chronic Pain And Inflammation Author: Bruno Chikly, M.D.2000 Publisher: I.H.H. Publishing, Arizona. Isbn Hard Cover = 0-9700530-5-3
Dec 2010
Morcaldi G, Boccardo F, Campisi C, Bellini T, Massocco D, Bonioli E.
Source
Department of Pediatrics, University of Genoa, Gaslini Children's Hospital, Italy. gmorcaldi@fastwebnet.it
Abstract
Kabuki syndrome was first described in Japan in 1981 as a rare disorder of unknown cause. Its main features include characteristic facies, postnatal growth retardation, and mental delay. To date, there is no molecular marker for Kabuki syndrome, which is considered genetically heterogeneous and still is a clinically-based diagnosis. Here we describe the first case of a patient affected by Kabuki syndrome associated with lymphatic dysplasia. We suggest accurate evaluation of all Kabuki patients as early as possible in order to diagnose lymphedema or other clinical manifestations of lymphatic system involvement. Early identification of lymphatic system maldevelopment provides the best chance for reducing the risk of developing progressive lymphedema with associated tissue changes (fibrosis, sclerosis, and fat deposition).
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Updated Jan. 21, 2012