HENNEKAM SYNDROME
Classified as a developmental disorder of the lymphatics. First described by Dutch physician R.C.M. Hennekam in 1989.
Generally presents with congenital lymphedema.
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 Syndrome
Multiple Congenital Anomaly/Mental Retardation (MCA/MR)
Syndromes
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.
http://www.nlm.nih.gov/cgi/jablonski/syndrome_cgi?index=339
...............................................
Hennekam Syndrome
HENNEKAM LYMPHANGIECTASIA-LYMPHEDEMA SYNDROME
| Syndrome | Hennekam syndrome |
|---|---|
| Synonym | intestinal lymphagiectasia-lymphedema-mental retardation syndrome |
| Personalia | Hennekam, R. C. M. (Dutch physician) |
| MeSH | Face / abnormalities |
| Growth Disorders | |
| Lymphangiectasis, Intestinal | |
| Lymphedema | |
| Seizures | |
| OMIM | 235510 |
| Summary | Intestinal lymphangiectasia; severe lymphedema of the limbs, genitalia, and face; facial anomalies; seizures; mild growth retardation; and moderate mental retardation. |
| Major Features | Head and neck: Lymphadematous flat facies, mild retrognathia, and occasional craniosynostosis. |
| Ears: Dysmorphic pinnae and atresia of ear canal. | |
| Eyes: Hypertelorism. | |
| Nose: Flat nasal bridge and epicanthal folds. | |
| Mouth and oral structures: Small mouth, narrow palate, flat upper lip, oligodonia, and conical crowns. | |
| Thorax: Narrow upper thorax. | |
| Extremities: Lymphedema of lower extremities. | |
| Skin: Infection of oozing lymph may cause erysipelas. | |
| Skin appendages: Alopecia areata, frontal upsweep, heavy eyebrows. | |
| Nervous system: Seizures. | |
| Cardiovascular system: Ventricular septal defect. | |
| Gastrointestinal system: Lymphagiectasia of the small intestine and rectal prolapse. | |
| Urogenital system: Genital lymphedema, kidney malformations, and vesicoureteral reflux. | |
| Immunologic system: Hypogammaglobulinemia. | |
| Biochemical and metabolic features: Hypoproteinemia and hypoalbuminemia. | |
| Growth and development: Growth and mental retardation. | |
| Heredity: The syndrome is familial and was first reported in two male and two female children of consanguineous parents. Transmitted as an autosomal recessive trait. | |
| Historical References | Hennekam RCM et al Autosomal recessive intestinal lymphangiectasia and lymphedema, with facial anomalies and mental retardation. Am J Med Genet, 1989, 34:593-600 |
| Mücke J et al Early onset lymphoedema, recessive form--a new form of genetic lymphoedema syndrome. Eur J Pediat, 1986, 145:195-8 | |
| Bibliography | Angle B, Hersh JH Expansion of the phenotype in Hennekam syndrome: A case with new manifestations. Am J Med Genet, 1997, 71:211-4 [MEDLINE] |
| Cormier-Daire V et al Craniosynostosis and kidney malformation in a case of Hennekam syndrome. Am J Med Genet, 1995, 57:66-8 [MEDLINE] | |
| Gabrielli O et al Intestinal lymphangiectasia, lymphedema, mental retardation, and typical face: Confirmation of the Hennekam syndrome. Am J Med Genet, 1991, 40:244-7 [MEDLINE] | |
| Yasunaga M et al Protein-loosing gastroenteropathy with facial anomaly and growth retardation: A mild case of Hennekam syndrome. Am J Med Genet, 1993, 45:477-80 [MEDLINE] |
http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?cmd=entry&id=235510
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Further Delineation of Hennekam Syndrome
1Ll
Al-Gazali, 2J.
Hertecant, 3R.
Ahmed, 4R. Padmanabhan
1UAE University Faculty of Medicine and
Health Sciences,
Paedatrics, PO Box 17666, Al Ain, UAE, 2Tawam
Hospital,
Paediatrics Dept., P.O. Box 15258, Al Ain, UAE, 3Al
Ain
Hospital, P.O. Box 1006, Al Ain, UAE, 4UAE
University Faculty
of Medicine and Health Sciences, Anatomy, PO Box 17666, Al Ain, UAE
Hennekam syndrome is an autosomal disorder characterized by midfacial hypoplasia, intestinal lymphangiectasia, peripheral lymphedema, seizures, growth retardation and variable degree of mental retardation (Hennekam et al., 1989 Am J Med Genet 34:593-600.). So far 24 cases have been reported in the literature. Van Balkom et a., 2002 Am J Med Genet 112:412-21) recently emphasized variability of the phenotypes of the syndrome and suggested the possible existence of phenocopies and genocopies. Here we report 4 children from four inbred Arab families with variable manifestation of Hennekam syndrome with additional features that were not previously reported. These include 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 haemangioma. That the lymphatics largely develop as outsproutings from the veins has been widely accepted now. Since anomalies of the veins and the consequent developmental abnormalities of the lymphatics might lead to alterations in the fluid balance of the embryos, we hypothesize that altered fluid dynamics due to defective vascular and lymphatic development may disrupt critical events in craniofacial morphogenesis, such as neural crest cell migration, and growth and differentiation of the facial primordia of neural crest origin resulting in Hennekam syndrome.
Other abstracts in same session
http://hgm2003.hgu.mrc.ac.uk/Abstracts/Publish/WorkshopPosters/WorkshopPoster02/hgm017.html
...............................................
Cutaneous manifestations and massive genital involvement in Hennekam syndrome
Pediatr Dermatol. 2006 May-Jun
Dermatology Clinic, University of Catania, Italy.
We describe a 16-year-old boy with intestinal lymphangiectasia, lymphedema of the limbs and genitalia, mild mental retardation, and facial anomalies (Hennekam syndrome) and cutaneous lesions. Severe edema in the genital area created a gigantic mass that included the scrotum and penis. Numerous grouped red-violaceous pseudo-vesicular lesions and plaques, as well as verrucous brown papules, were present on the penis and scrotum. The prepuce was hypertrophic, with severe phimosis. Histologic analysis revealed dilated lymphatic vessels lined by a discontinuous layer of flat endothelial cells in the papillary dermis and extending down to the reticular dermis. Dilated blood vessels were also present but no cellular abnormalities were identified. A diagnosis of superficial cutaneous lymphatic malformations was made. To the best of our knowledge, this is the first detailed cutaneous histologic investigation in a patient with Hennekam syndrome. We assume that the onset of cutaneous lesions in our patient was likely triggered by a generalized worsening of his lymphedema.
...............................................
Lymphedema-lymphangiectasia-mental retardation (Hennekam) syndrome: a review
Am J Med Genet. 2002 Nov
Child- and Adolescent Psychiatry Clinic, Oranjestad, Aruba, Dutch West Indies.
The Hennekam syndrome is an infrequently reported heritable entity characterized by lymphedema, lymphangiectasia, and developmental delay. Here we add an additional 8 patients, and compare their findings to the 16 cases from the literature. The lymphedema is usually congenital, can be markedly asymmetrical, and, often, gradually progressive. Complications such as erysipelas are common. The lymphangiectasias are present in the intestines, but have also been found in the pleura, pericardium, thyroid gland, and kidney. Several patients have demonstrated congenital cardiac and blood vessel anomalies, pointing to a disturbance of angiogenesis in at least some of the patients. Facial features are variable, and are chiefly characterized, in a typical patient, by a flat face, flat and broad nasal bridge, and hypertelorism. Facial features are thought to mirror the extent of intrauterine facial lymphedema, or may be caused by lymphatic obstruction that affects the early migration of neural crest tissue. Other anomalies have included glaucoma, dental anomalies, hearing loss, and renal anomalies. The psychomotor development varies widely, even within a single family, from almost normal development to severe mental retardation. Convulsions are common. The existence of 10 familial cases, equal sex ratio, increased parental consanguinity rate (4/20 families), and absence of vertical transmission are consistent with an autosomal recessive pattern of inheritance. It seems likely that most (but not all) manifestations of the entity can be explained as sequences of impaired prenatal and postnatal lymphatic flow, suggesting that the causative gene(s) should have a major function in lymphangiogenesis. Copyright 2002 Wiley-Liss, Inc.
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Exudative enteropathy in congenital lymphedema-lymphangiectasia syndrome
Klin Padiatr. 2006 Jan-Feb
Abt. Kinder- und Jugendmedizin, HELIOS Krankenhaus, Leisnig.
Key Words: Hennekam syndrome - lymphangiectasia-lymphedema syndrome - exudative enteropathy
BACKGROUND: Congenital peripheral elephantiasiformic alterations are very rare in paediatric patients. In a patient with lymphangiectasia-lymphedema syndrome we demonstrate over a 8-year follow-up that not only cosmetic and social indications for surgical treatments but also internal care become important during the course.
PATIENT: We report on a boy with congenital lymphedemas of the extremities and the genital region, which were several times surgically treated. The patient became symptomatic firstly with tetanic cramps caused by malabsorption syndrome due to intestinal lymphangiectasia at the age of 6 years. Synopsis of clinical and laboratory findings and the patient's course are pointing to a mild Hennekam syndrome with still unknown aetiology.
RESULTS: The boy developed adequately with permanent oral substitution of electrolytes and vitamins, protein-rich diet, supplementation of medium-chain fatty acids and compressing bandages. Infusions of human albumin to correct persistent hypalbuminemia as well as cytostatic treatment with cyclophosphamide as a formal trial were ineffective and are not advisable, therefore.
...............................................
Early death in two sisters with Hennekam
syndrome.
Scarcella A, De Lucia A, Pasquariello MB, Gambardella P.
Dipartimento di Pediatria, University of Naples, Federico II, Italy.
aldscarc@unina.it
We report on two sisters with facial anomalies,
protein-losing
enteropathy, and
intestinal lymphangiectasia consistent with the diagnosis of Hennekam
syndrome.
Both patients had a number of other anomalies not previously described
in this
autosomal recessive disorder, i.e., primary hypothyroidism,
hypertrophic pyloric
stenosis, and an early fatal outcome. These cases support the autosomal
recessive transmission and the expansion of the phenotype of the
Hennekam
syndrome.
Publication Types: PubMed
...............................................
Elisabeth Rosser, Scheimberg I, Barnick C.
Hennekam syndrome (HS) is a rare disorder comprising intestinal lymphangiectasia and lymphodema of the limbs, together with a dysmorphic facial appearance and mental retardation. The facial features include hypertelorism with a wide, flat nasal bridge, epicanthyic folds, small mouth and small ears. Gum hypertrophy has also been described. The condition seems to be inherited in an autosomal recessive manner. We describe the first pregnancy of a Caucasian couple who are not known to be consanguineous. Ultrasound scanning at 12 weeks gestation demonstrated increased nuchal thickening; karyotyping showed normal female chromosomes but the pregnancy continues to be scanned regularly. Scans at 17 weeks gestation revealed a pericardial effusion but detailed cardiac scans did not demonstrate a structural abnormality. Infection screens were negative. Generalises oedema and pleural effusions were seen on later scans, and the infant was born by SVD at 27 weeks gestation. Resuscitation at birth was unsuccessful. The infant was dysmorphic with hypertelorism, a beaked nose, a long philtrum and low set ears. There was also gingival hypertrophy, a mild pectus excavatum, rocker bottom feet and a vaginal prolapse. Pot mortem examination demonstrated an ostium secumdum, intestinal malrotation and a large anterior fontanelle with a fused posterior fontanelle. A search using the LDDB suggested several conditions, including HS. The pathology of the intestine and lungs was reviewed and submucosal lymphangiectasia was seen in both organs. We believe that these findings substantiate the diagnosis of HS. We are not aware of any previous reports of the condition proving to be lethal in the perinatal period. The lymphangiectasia was detected only when the pathology was reviewed; the diagnosis should perhaps be considered in other infants with unexplained pericardial or pleural effusions.
* *Link No Longer Available**
======================
External Links:
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Hennekam syndrome - Definition
"Intestinal lymphangiectasia; severe lymphedema of the limbs,
genitalia,
and face; facial anomalies; seizures; mild growth retardation; and
moderate
mental retardation."
http://www.diseasesdatabase.com/umlsdef.asp?glngUserChoice=32192
........................
Hennekam’s Syndrome:
Lymphoedema of face, genitals, and limbs; the face and nose are flat, the mouth narrow, the chin large, the ear malformed, the eyes protruding, the fingers can be webbed, the thumb large. There can be mild mental retardation. [Autosomal Recessive]
Ackowledgement
Lymphoedema Association of Australia[/b]
www.lymphoedema.org.au
........................
Hennekam lymphangiectasia lymphedema syndrome
........................
Severe lymphedema, intestinal lymphangiectasia, seizures and mild mental retardation: further case of Hennekam syndrome with a severe phenotype.
........................
Intestinal lymphangiectasia, lymphedema, mental retardation, and typical face: confirmation of the Hennekam syndrome.
........................
Expansion of the phenotype in Hennekam syndrome: a case with new manifestations.
........................
Craniosynostosis and kidney malformation in a case of Hennekam syndrome.
........................
Two brothers with Hennekam syndrome and cerebral abnormalities.
........................
Lymphoscintigraphic manifestations of Hennekam syndrome--a case report.
........................
Hennekam syndrome presenting as nonimmune hydrops fetalis, congenital chylothorax, and congenital pulmonary lymphangiectasia.
........................
Severe lymphedema, intestinal lymphangiectasia, seizures and mild mental retardation: further case of Hennekam syndrome with a severe phenotype.
=======================
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=======================
ICD10 - ICD9 External Resources
* No ICD-10
* No Specific ICD-9
2008 ICD-9-CM Volume 1 Diagnosis Codes Home > Diseases Of The Digestive System 520-579 > Other Diseases Of Digestive System 570-579 > Intestinal Malabsorption 579.*
Human Disease and Mouse Model Detail
Term:
Hennekam Lymphangiectasia-Lymphedema
Syndrome
OMIM ID: 235510
There are currently no human or mouse genes associated with this disease in the MGI database.
=======================
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Lipodema Lipoedema
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DISCRIPTION
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Sentinel
Node Biopsy
http://www.lymphedemapeople.com/wiki/doku.php?id=sentinel_node_biopsy
Small
Needle Biopsy - Fine Needle Aspiration
http://www.lymphedemapeople.com/wiki/doku.php?id=small_needle_biopsy
Magnetic
Resonance Imaging
http://www.lymphedemapeople.com/wiki/doku.php?id=magnetic_resonance_imaging
Lymphedema
Gene FOXC2
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_foxc2
Lymphedema Gene VEGFC
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_vegfc
Lymphedema Gene SOX18
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_gene_sox18
Lymphedema
and
Pregnancy
http://www.lymphedemapeople.com/wiki/doku.php?id=lymphedema_and_pregnancy
Home page: Lymphedema People
http://www.lymphedemapeople.com
Page Updated: April 16, 2008