Syndromes Associated With Lymphatic Dysplasia - Page Four
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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.
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
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.
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
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.
Noonan syndrome (NS) is clinically similar to Turner syndrome but with a normal number of chromosomes.
1. Craniofacial manifestations
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:
Short stature or dwarfism
Cryptorchidism (undescended testicles) (60%)
3. Musculoskeletal manifestations
Cubitus valgus (50%)
Superior pectus carinatum (90-95%) (“pigeon breast”)
Inferior pectus excavatum (concave chest, “funnel breast”)
low-set widespaced nipples
Dental malocclusion (35%)
Short curved fingers with blunt fingertips (30%),
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.
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%)
7. Hematologic manifestations
Coagulation defects (33%)
- Partial deficiency of factor XI:C, XII:C, and VIII:C
- Von Willebrand disease
8. Ophthalmologic manifestations
Strabismus (about 55%)
9. Dermatologic manifestations
Large finger pads (67%)
10. Otologic manifestations
Mild hearing loss or deafness (12%)