Renal Lymphangiectasia

Lorenz T. Ramseyer, MD

1 From Bass Baptist Memorial Hospital, 600 S Monroe, Enid, OK 73701. Received May 28, 1999; revision requested July 20; revision received August 26; accepted August 30. Address correspondence to the author (e-mail: lramseyer@peakonline.com).
Index terms: Diagnosis Please • Kidney, CT, 81.12112 • Lymphatic system, abnormalities, 994.829 • Lymphatic system, CT, 994.12912 • Urography, 81.11

History

28-year-old obese man had microscopic hematuria. Physical examination results were normal. His medical history was unremarkable, and there was no pertinent family history. Excretory urography (Fig 1) and computed tomography (CT) of the abdomen (Fig 2) were performed after oral and intravenous administration of contrast material.

Imaging Findings

The excretory urogram demonstrated bilateral nephromegaly with distortion of the pelvocaliceal systems (Fig 1). The CT scan of the abdomen (Fig 2) showed fluid collections in the perinephric space bilaterally, surrounding the renal cortex. In addition, there were peripelvic fluid collections bilaterally, with distortion of the pelvocaliceal systems. There were fluid collections in the retroperitoneum that crossed the midline at the level of the renal hila, adjacent to the abdominal aorta and the inferior vena cava.

Discussion

Several differential diagnostic possibilities are to be considered with bilateral nephromegaly with pelvocaliceal splaying and distortion. Adult polycystic kidney disease, lymphoma, nephroblastomatosis, and other causes of multiple renal masses, such as von Hippel-Lindau disease and tuberous sclerosis, are considerations. Adult polycystic kidney disease has characteristic findings of numerous bilateral renal cysts, with or without hepatic or pancreatic cysts. The cysts typically vary in size and are scattered throughout the parenchyma. Lymphoma and other malignancies can demonstrate soft-tissue masses involving the kidneys, pelvocaliceal systems, or retroperitoneum. The fluid attenuation of the perinephric collections in the test case, as evidenced by attenuation measurements of 0–10 HU in Figure 2c, exclude lymphoma and other soft-tissue masses. Perinephric and retroperitoneal soft-tissue masses can be seen in retroperitoneal fibrosis but are again excluded by the fluid attenuation in the test case. Nephroblastomatosis is a cause of nephromegaly in children and is characterized by multiple subcapsular and parenchymal soft-tissue nodules composed of metanephric blastema (1).

Renal lymphangiectasia is a rare disorder. Patient symptoms described in the literature (2–4) include hematuria, flank pain, and abdominal pain. The condition has been found in children and in adults (2,4–7). The origin of this disorder is speculative. There is a familial association in some cases, which argues for a congenital cause (6). There was no known family history of renal lymphangiectasia in the test case. Others argue for an acquired cause, which suggests that the lymphatic vessels may become blocked owing to inflammation or other obstruction and so cause lymphatic ectasia (8). Others have suggested that these lesions may be a true neoplasm (9). The nomenclature of this disorder is confusing and has evolved in recent years. Other names have included "renal lymphangiomatosis" (3,6), "renal lymphangioma" (5), "peripelvic lymphangiectasia" (2), and "renal peripelvic multicystic lymphangiectasia" (8). "Renal lymphangiectasia" is the preferred name, given that the disorder is characterized by ectatic perirenal, peripelvic, and intrarenal lymphatic vessels (10,11).

Imaging findings of renal lymphangiectasia include peripelvic cysts and perirenal fluid collections. The finding of retroperitoneal fluid collections, presumably dilated lymphatic vessels, is a more variable finding but has been noted in multiple cases in the literature (2–4,6).

Renal lymphangiectasia has been found associated with renal venous thrombosis and hypertension (4,6,12). Ascites and large perinephric fluid collections have been found and are exacerbated by pregnancy (6). The natural history of this disorder is not completely understood.

In a neonatal case, partial regression was reported (7).

The diagnosis of renal lymphangiectasia can be confirmed with needle aspiration of chylous fluid from the perinephric fluid collections (4). However, the ultrasonographic and CT findings are characteristic for this disease and allow the diagnosis to be made confidently (2,6). Treatment is not usually necessary. Complicated cases may be treated with nephrectomy, percutaneous drainage, or marsupialization (4).

In the case presented here, the diagnosis of renal lymphangiectasia was based on the characteristic CT findings. The perirenal, peripelvic, and retroperitoneal collections had attenuation measurements consistent with fluid (0–10 HU) rather than with the soft-tissue attenuation seen with lymphoma or other causes of bilateral renal soft-tissue masses (Fig 2c). No invasive procedures to confirm diagnosis were deemed appropriate for this patient.

Our congratulations to the 26 individuals who submitted the most likely diagnosis (renal lymphangiectasia) for Diagnosis Please, Case 34. The names and locations of the individuals, as submitted, are as follows

Marc P. Banner, Philadelphia, Pa
Lawrence R. Bigongiari, MD, Hope, Ark
Marc G. de Baets, MD, Lugano, Switzerland
Kemal Demir, MD, Ataköy, stanbul, Turkey
Giovanna Demurtas, MD, Cagliari, Italy
Luis E. Fajre, MD, Tucuman, Argentina
Sandra K. Fernbach, Chicago, Ill
Milton R. Fuentealba, MD, General Roca, Rio Negro, Argentina
Celso Ichihara, Brazil

Radiology - Renal Lymphangiectasia

* Full Report and Diagnostic Imaging

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Pub Med Links Page

See Also:

Lymphedema People

Hennekam Lymphangiectasia

Intestinal Lymphangiectasia

Pulmonary Lymphangiectasia

Lymphangiectasia

Hennekam Syndrome

Pulmonary Cystic Lymphangiectasis

All About Lymphangiectasia Yahoo Support Group

Support group for parents, patients, children who suffer from all forms of lymphangiectasia. This condition is caused by dilation of the lymphatics. It can affect the intestinal tract, lungs and other critical body areas.

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Pulmonary Lymphangiectasia

CONGENITAL PULMONARY LYMPHANGIECTASIA

DEFINITION:

A congenital disease involving the lung characterized by greatly dilated lymphatic ducts throughout the lung.

EPIDEMIOLOGY:

incidence: ?
age of onset:neonatal period and after the neonatal period
risk factors:Noonan's SyndromeTurner's Syndrome

TYPES (after Noonon (1970))*:

Group I

dilated pulmonary lymphatics are part of a generalized form of lymphangiectasis: thoracic and extrathoracic (intestinal) lymphangiectasiaassociated with lymphedemahemi hypertrophy diffuse angiomatosis in which bone is the most common site of involvementless severe form and has a much better prognosis than the other two forms2.

Group II

due to a cardiac lesiondilated pulmonary lymphatics are acquired in utero due to obstruction of the pulmonary venous flow secondary to a cardiac lesion which may interfere with the normal regression of the lymphatic tissue elements after the 16th week of fetal life
very poor prognosis

Group III

due to a defect in the primary development of the lungLawrence (1955) postulated that lymphangectasis is due to a developmental error in which the normal regression of connective tissue elements in the lung fails to occur after the 16th week of life. Subsequently the lymph vessels do not regress in size and remain enlarged in relation to the parenchyma of the lung (Noonan, 1970).

male predominance
may be associated with congenital malformations including cardiac lesions clinical picture characterized by over expanded lungs with alveolar hypoventilation and periodic wheezing and a relapsing course
dilated lymphatics may result in marked restriction of respiratory movements
poor prognosis

*first report of CPL by Virchow (1856) and first named by Lawarence in 1955

CLINICAL FEATURES:

presents in two forms:

1. Neonatal Period presents with respiratory distress and cyanosis at birth(usually term) with rapid demisecan also present as a stillbirth

2. Post Neonatal Period presents with respiratory difficultiesprogressive relapsing courseassociated with chylopericardium, chylothorax, chronic cough, congestive heart failure

3. Associated Abnormalities congenital abnormalities in 50% of cases:

1. CardiacTAPVR, mitral valve atresia, hypoplastic left heart, aortic coarctation, VSD, PDA, ASD

2. Otherscystic hygromas, diffuse angiomatosis (bones), pneumothorax

INVESTIGATIONS:

A. Diagnostic

1. Lung Biopsycystic dilation of the lymphatics in the subpleural and intralobular regions and perivascular spaces give the lungs a subpleural reticulated pattern of fine interconnecting white lines with air-filled cystic areas

B. Imaging Studies

1. Chest X-Ray
hyperexpansion
diffuse reticular pattern

MANAGEMENT:

supportive

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See Also

Pulmonary Lymphangiectasia

Lymphedema People

Intestinal Lymphangiectasia - Waldmann Disease

Hennekam Lymphangiectasia

All About Lymphangiectasia Yahoo Support Group

Support group for parents, patients, children who suffer from all forms of lymphangiectasia. This condition is caused by dilation of the lymphatics. It can affect the intestinal tract, lungs and other critical body areas.

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Intestinal Lymphangiectasia

Also Known As: Waldmann Disease

Synonyms

Dysproteinemia, Familial
Enteropathy, Hypercatabolic Protein-Losing
Familial Hypoproteinemia with Lymphangietatic Enteropathy
Hypoproteinemia, Idiopathic
Intestinal Lymphangiectasia
Intestinal Lymphangiectasis
Lymphangiectasia, Primary Intestinal
Lymphangiectasis, Primary Intestinal
Lymphangiectatic Protein-Losing Enteropathy
Lymphedema, Neonatal due to Exudative Enteropathy
Protein-Losing Enteropathy Secondary to Congestive Heart Failure

Lymphangiectasia is a condition wherein the lymphatics are dilated. The result is that lymph channels may become blocked and there is a "leakage" of fluid into the affected body area.

Signs and symptoms

Symptoms include diarrhea, nausea, vomiting, fatty stools, and abdominal pain may be present. Other indicators may include edema, low protein levels (caused from the protein loss from the condition), and low albumin levels.

Histology

Malformation or dilation of lymphatic channels resulting in lymph blockages and accumulation of fluids in the affected body areas.

Aetiology

This condition can either be primary (hereditary), primary (congenital) or can be secondary as a result of cancers, cardiac conditions, chronic inflammations, tuberculosis, scleroderma, lupus, fibrosis, endometriosis as well as other factors.

Treatment

There is no cure for lymphangiectasia. Treatment is focused on control of complications, control through dietary habits and possible drug therapy for various symptoms. In the case of secondary lymphangiectasia treatment also focuses on the underlying cause.

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Synonyms and related keywords:

primary intestinal lymphangiectasia, congenital intestinal lymphangiectasia, Milroy disease, protein-losing gastroenteropathies, hypoproteinemia, lymphocytopenia, hypogammaglobulinemia, anergy, impaired allograft rejection, diarrhea, peripheral edema

Author: Raoul Joubran, MD Chief, Fellow, Department of Internal Medicine, Division of Gastroenterology/Hepatology, University of Louisville School of Medicine

Background: Traditionally, protein-losing gastroenteropathies have been classified into 3 groups (depending on the mechanism of their etiology), which include (1) those causing mucosal damage leading to increased permeability to protein (usually not involving mucosal ulcerations), (2) those with mucosal erosions and/or ulcerations, and (3) those in which protein loss is secondary to mechanical lymphatic obstruction. While a more detailed discussion on Protein-Losing Enteropathy

E-Medicine

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For Further Information:

Intestinal Lymphangiectasia

Lymphedema People

Pulmonary Lymphangiectasia

All About Lymphangiectasia Yahoo Support Group

Support group for parents, patients, children who suffer from all forms of lymphangiectasia. This condition is caused by dilation of the lymphatics. It can affect the intestinal tract, lungs and other critical body areas.

Subscribe: allaboutlymphangiectasia-subscribe@yahoogroups.com

. . . . . .

Pub Med Related Links Page

Waldmann Disease - Intestinal Lymphangiectasia

Hennekam Lymphangiectasia

Classified as a developmental disorder of the lymphatics.

First described by Dutch physician R.C.M. Hennekam in 1989.

Clinical

Characteristics include Intestinal or pleural lymphangiectasia was accompanied by the usual hypoproteinemia, hypogammaglobulinemia, and lymphocytopenia. Facial anomalies included flat face, flat nasal bridge, hypertelorism, epicanthal folds, small mouth, tooth anomalies, and ear defects. Complications involve severe lymphedema cellulitis and erysipelas.

There is no specific treatment for the condition, only management of the complications. Also, related to Turner Syndrome.

Histology

Malformation or dilation of lymphatic channels resulting in lymph blockages and accumulation of fluids in the affected body areas.

Etiology

This condition can either be primary (hereditary), primary (congenital) or can be secondary as a result of cancers, cardiac conditions, tuberculosis, scleroderma, lupus, fibrosis, endometriosis as well as other factors.

Treatment

There is no cure for lymphangiectasia. Treatment is focused on control of complications, control through dietary habits and possible drug therapy for various symptoms.

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Hennekam SyndromeMultiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes

%235510 HENNEKAM LYMPHANGIECTASIA-LYMPHEDEMA SYNDROME

TEXT

Hennekam et al. (1989) described a syndrome of intestinal lymphangiectasia with severe lymphedema of the limbs, genitalia and face, and severe mental retardation. Intestinal lymphangiectasia was accompanied by the usual hypoproteinemia, hypogammaglobulinemia, and lymphocytopenia. Facial anomalies included flat face, flat nasal bridge, hypertelorism, epicanthal folds, small mouth, tooth anomalies, and ear defects. The facial appearance was Oriental. Down syndrome had been suspected in some of the patients. The patients had seizures. Erysipelas was a problem complicating the edema of the legs. Autosomal recessive inheritance was strongly supported by the occurrence of the disorder in 2 males and 2 females of 2 sibships from parents who shared a common ancestral couple. Hennekam et al. (1989) reviewed genetic syndromes with lymphangiectasia and lymphedema as features.

Gabrielli et al. (1991) reported a male, born of second-cousin parents, with facial anomalies, syndactyly of the fingers, equinovarus feet, and cryptorchidism were present at birth. He had had soft and abundant feces most of his life. He was first hospitalized at age 4 for leg edema and was found to have hypoalbuminemia, hypogammaglobulinemia, and lymphopenia. Conductive hearing loss was demonstrated at age 9 years. Gabrielli et al. (1991) provided photographs of the patient at age 14 years. The typical face was characterized by flat midface, flat nasal bridge, hypertelorism, epicanthal folds, small mouth, tooth anomalies, and small ears. The hand showed cutaneous syndactyly and camptodactyly. Seizures were thought to be related to hypocalcemia; however, it would seem that the ionized calcium may be normal. Pachygyria was demonstrated which may account for mental retardation and seizures.

Yasunaga et al. (1993) described the case of a 7-year-old boy with protein-losing gastroenteropathy. He had a face typical of Hennekam syndrome, including flat nasal bridge, hypertelorism, small mouth and tooth anomalies, but did not have mental retardation or severe lymphedema. Yasunaga et al. (1993) suggested that the child had a mild form of Hennekam syndrome. Study of the family in 3 generations suggested that heterozygotes may have some of the facial features.
Cormier-Daire et al. (1995) described a girl with intestinal lymphangiectasia, severe lymphedema of the limbs, seizures, mild mental retardation, and facial anomalies consistent with the diagnosis of Hennekam syndrome. In addition, she had an ectopic kidney and craniosynostosis of the coronal suture, 2 manifestations not previously reported in this disorder.

Scarcella et al. (2000) described 2 sisters with facial anomalies, protein-losing enteropathy, and intestinal lymphangiectasia consistent with the diagnosis of Hennekam syndrome. Both had a number of other anomalies not previously described in this disorder: primary hypothyroidism, hypertrophic pyloric stenosis, and an early fatal outcome at 8 and 3 months, respectively.

Polyhydramnios complicated each pregnancy in the third trimester. At birth the older sister had flat face with flat and broad nasal bridge, short philtrum, hypertelorism, gingival hypertrophy, and mild retrognathia; the younger sister had similar features. Hepatosplenomegaly and lymphedema of the limbs developed in the first month of life in the first born. She died from a severe septic event at 8 months of age, after having recurrent gastroenteric and respiratory infections associated with severe hypogammaglobulinemia. Autopsy showed extensive lymphangiomatosis of the mediastinum, pleura and peritoneum, and intestinal lymphangiectasia. Fetal hepatomegaly was detected in the second born, who died at 3 months of age from cardiac failure due to severe refractory hypoproteinemia.

Forzano et al. (2002) reported an Italian patient with severe lymphedema of the lower limbs, genitalia, and face, intestinal lymphangiectasia, seizures, and moderate mental retardation. He had a flat face, depressed nasal bridge, and hypertelorism. Forzano et al. (2002) proposed that the patient had a severe form of Hennekam syndrome.

Van Balkom et al. (2002) reported 8 patients with Hennekam syndrome and compared their findings with those of the 16 previously reported cases. Lymphedema was usually congenital, sometimes markedly asymmetric, and often gradually progressive. Complications, such as erysipelas, were common. Lymphangiectasias were found in the intestines and occasionally in the pleura, pericardium, thyroid gland, and kidney. Several patients demonstrated congenital cardiac and blood vessel anomalies, suggesting a disturbance in angiogenesis. Typical facial features included flat face, flat and broad nasal bridge, and hypertelorism, but the features were variable and thought to mirror the extent of intrauterine facial lymphedema. Other anomalies included glaucoma, dental anomalies, hearing loss, and renal anomalies. Psychomotor development varied widely, even within a single family, from almost normal development to severe mental retardation. Convulsions were common. The existence of 10 familial cases, equal sex ratio, increased parental consanguinity rate, and absence of vertical transmission were consistent with an autosomal recessive pattern of inheritance.

Bellini et al. (2003) described a female infant with congenital lymphedema, facial anomalies, and intestinal lymphangiectasia consistent with a diagnosis of Hennekam syndrome. At birth, the patient presented with severe respiratory distress due to nonimmune hydrops fetalis, a congenital chylothorax, and pulmonary lymphangiectasia.

Al-Gazali et al. (2003) reported 4 children from 4 inbred Arab families with varying manifestations of Hennekam syndrome as well as additional features, including abnormalities of the middle ear, anomalous pulmonary venous drainage, interrupted inferior vena cava, polysplenia, crossed renal ectopia, median position of the liver, and multiple cavernous haemangiomas. Since anomalies of the veins and the consequent developmental abnormalities of the lymphatics might lead to alterations in the fluid balance of the embryo, Al-Gazali et al. (2003) hypothesized that altered fluid dynamics due to defective vascular and lymphatic development might disrupt critical events in craniofacial morphogenesis, resulting in Hennekam syndrome.

Multiple Congenital Anomaly/Mental Retardation (MCA/MR) Syndromes

For Further Information:

Hennekem Lymphangiectasia

Lymphedema People

All About Lymphangiectasia Yahoo Support Group

Support group for parents, patients, children who suffer from all forms of lymphangiectasia. This condition is caused by dilation of the lymphatics. It can affect the intestinal tract, lungs and other critical body areas.

Subscribe: allaboutlymphangiectasia-subscribe@yahoogroups.com

Intestinal Lymphangiectasia

Pulmonary Lymphangiectasia

Diseases and Disorders of the Lymphatic System

Castleman's Disease

Peom's Syndrome

Related Terms: Angiofollicular hyperplasia, Giant lymph node hyperplasia, Angiofollicular Lymph Node Hyperplasia, Angiomatous Lymphoid, Giant Benign Lymphoma, Hamartoma of the Lymphatics, Poems Syndrome

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Cutaneous B-Cell Lymphoma

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Cutaneous T-Cell Lymphoma

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Cystic Hygroma

Related Terms: Lymphatic dysplasia, cystic swelling, hydroma, cervical hygroma, hygroma colli cysticum, hygroma of the neck, hygroma axillare, hygroma of the axilla, lymphedema, encephaloceles, meningomyelocele

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Duncan's Syndrome

Lymphoproliferative Disorder

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Hidradenitis Suppurativa

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Kawasaki Disease

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Lipoedema, Lipodema, Lipedema

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Lymphangiomatosis

Gorham's Vanishing Bone Disease

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Lymphadenopathy

Related Terms: Adenopathy, lymph node enlargement, lymph node disease

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Lymphangiomas

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Lymphangitis

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Lymphatic Filariasis

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Lymphatic Malformations

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Lymphedema

RELATED TERMS: Hereditary Lymphedema, Type I; Congenital Hereditary Lymphedema Milroy Disease, Nonne-Milroy-Meige Syndrome, Hereditary Lymphedema, Type II, Meige's Lymphedema, Familial Lymphedema Praecox, Hereditary Lymphedema Tarda, Hereditary Angioedema, Lymphedema (Traumatic), Elephantiasis, Distichiasis-Lymphedema Syndrome Lymphedema and Ptosis, The lymph system, Lymphorrhea, Lymphedema wounds, Weeping lymphedema, Cellulitis, Lymphangitis, Secondary lymphedema, Lymphedema complications, Lymphedema Stages, Lymphedema treatment, Decongestive therapy, Risk factors for lymphedema, lymphedema fibrosis, Lymphedema complications, Lymphedema Praecox, Temporary lymphedema, Chronic lymphedema, Autosomal genetic trait, Emotional impact of lymphedema, Spreading lymphedema

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Lymphoceles

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Lymphoma

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Hodgkins Lymphoma

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Panniculitis

Info Page Links for Developmental Disorders of the Lymphatics

Syndromes Associated with Lymphatic Dysplasia

Aagenaes Syndrome

Aarskog Syndrome

Alpha Galactosidase B Deficiency

Avasthey Roy Syndrome

Cholestasis Syndrome

Crohn's Disease

Congenital Disorder of Glycosylation Type 1B

Congenital Recessive Syndrome

Distichiasis

Dysplasia Anhidrotic Immunodeficiency Oledaid

Ectodermal dysplasia hypohidrotic immune deficiency

Fabry's Disease

Figueroa Syndrome

German Syndrome

Hennekam Syndrome

Hereditary Syndromes

Hypotrichosis Lymphedema

Idiopathic Hydrops Fetalis

Jeken's syndrome

Kasabach Merritt Syndrome

Klippel Trenaunay Weber

Klinefelter Syndrome

Lissencephaly Syndrome

Lymphangiectasia

Lymphangiectasia - Hennekam

Lymphangiectasia - Intestinal

Lymphangiectasia - Pulmonary

Lymphangiectasia - Renal

Lymphedema Atrial Septal Defect

Lymphedema Campomelia Cumming

Lymphedema Hypoparathyroidism Syndrome

Lymphedema Osteopetrosis Ectodermal

Maffuccis Syndrome

Melkersson Rosenthal Syndrome

Micropehaly Chorioretinopathy Syndrome

Nevo Syndrome

Noonan Syndrome

Peho Syndrome

Phelan-McDermid Syndrome - 22q13 Deletion

Prolidase Deficiency

Ptosis Syndrome

Pulmonary Cystic Lymphangiectasis

Sharp Aagenaes Syndrome

Swyer Syndrome

Trisomy 10

Trisomy 13

Trisomy 18

Trisomy 21

Trisomy 22

Trisomy Disorders

Turner Syndrome

Von Recklinghausen Neurofibromatosis

Waldmann Disease

Yellow Nail Syndrome

Syndromes Associated with Lymphatic Dysplasia - Page Seven

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http://www.lymphedemapeople.com

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Other Syndromes Associated With Lymphatic Dysplasia

*Aarskog syndrome

(short stature, hypertelorism, and abnormal scrotum). Probably X-linked recessive disorder.

*Alpha-Galactosidase B deficiency (Galb) or N-Acetyl-Alpha-D-Galactosaminidase deficiency (NAGA).

These syndromes may lead to progressive neurologic abnormalities (psychomotor retardation).

Gene location: 22q11.

*Congenital disorder of Glycosylation, Type Ib (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).

*Hypotrichosis-Lymphedema-Telangiectasia Syndrome (Hlts)

Gene location: 20q13.33

*Idiopathic Hydrops Fetalis

(generalized edema of the fetus of non immunologic origin)

*Intestinal Lymphangiectasia.

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 syndrome

(lissencephaly is characterized by microcephaly and a thickened cortex), Norman-Roberts Type. Gene location: 7q22.

*Lymphedema-Atrial Septal Defect-Facial Changes

*Lymphedema-Campomelia Cumming type (Cumming, W. A.; 1986).

Campomelia is characterized by an abnormal curvature of the long bones, especially from lower extremities.

*Lymphedema-Cerebral Arteriovenous malformations

*Lymphedema-Microcephaly-Chorioretinopathy

*Lymphedema-Ptosis (eyelids).

Gene location: 16q24.3.

*Lymphedema- Osteopetrosis-Ectodermal

*Dysplasia-Anhidrotic-Immunodeficiency or OL-EDA-ID syndrome (Duffinger et al. 2001).

Gene location: Xq28.

*Pulmonary Cystic Lymphangiectasis (Franck J., Pipper P.G., 1959)

*Nevo Syndrome

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:

Progressive encephalopathy with edema, hypsarrhythmia, and optic atrophy (Salonen R. et al, 1991)

*Prolidase deficiency (PEPD).

Include: 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

*Swyer syndrome, Gonadal dysgenesis, XY female type.

Pateints are female that do not develop secondary sexual characteristics at puberty and present streak gonads.

Gene location: Xp22.11-p21.2.

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(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

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Syndromes Associated with Lymphatic Dysplasia - Page Six

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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: 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
- Gonadal dysgenesis usually leads to primary or secondary amenorrhea (95%)
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

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Von Recklinghausen Neurofibromatosis type 1 (NF1)

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,

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Yellow nail syndrome:

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

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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.

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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

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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)

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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

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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

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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

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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.

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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%)

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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.

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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- 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)

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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.

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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.

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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 internal organs, the head and neck area, or the extremities).

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Distichiasis (a.k.a. Lymphedema-Distichiasis) syndrome

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

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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

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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

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