Hennekam Lymphangiectasia Syndrome

HENNEKAM LYMPHANGIECTASIA SYNDROME

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 syndrome - Definition"Intestinal lymphangiectasia; severe lymphedema of the limbs, genitalia, and face; facial anomalies; seizures; mild growth retardation; and moderate mental retardation.

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.

REFERENCES

1. Al-Gazali, L. I.; Hertecant, J.; Ahmed, R.; Khan, N. A.; Padmanabhan, R. :
Further delineation of Hennekam syndrome. Clin. Dysmorph. 12: 227-232, 2003.PubMed ID : 14564208
2. Bellini, C.; Mazzella, M.; Arioni, C.; Campisi, C.; Taddei, G.; Toma, P.; Boccardo, F.; Hennekam, R. C.; Serra, G. :
Hennekam syndrome presenting as nonimmune hydrops fetalis, congenital chylothorax, and congenital pulmonary lymphangiectasia. Am. J. Med. Genet. 120A: 92-96, 2003.PubMed ID : 12794699
3. Cormier-Daire, V.; Lyonnet, S.; Lehnert, A.; Martin, D.; Salomon, R.; Patey, N.; Broyer, M.; Ricour, C.; Munnich, A. :
Craniosynostosis and kidney malformation in a case of Hennekam syndrome. Am. J. Med. Genet. 57: 66-68, 1995.PubMed ID : 7645602
4. Forzano, F.; Faravelli, F.; Loy, A.; Di Rocco, M. :
Severe lymphedema, intestinal lymphangiectasia, seizures and mild mental retardation: further case of Hennekam syndrome with a severe phenotype. Am. J. Med. Genet. 111: 68-70, 2002.PubMed ID : 12124738
5. Gabrielli, O.; Catassi, C.; Carlucci, A.; Coppa, G. V.; Giorgi, P. :
Intestinal lymphangiectasia, lymphedema, mental retardation, and typical face: confirmation of the Hennekam syndrome. Am. J. Med. Genet. 40: 244-247, 1991.PubMed ID : 1897580
6. Hennekam, R. C. M.; Geerdink, R. A.; Hamel, B. C. J.; Hennekam, F. A. M.; Kraus, P.; Rammeloo, J. A.; Tillemans, A. A. W. :
Autosomal recessive intestinal lymphangiectasia and lymphedema, with facial anomalies and mental retardation. Am. J. Med. Genet. 34: 593-600, 1989.PubMed ID : 2624276
7. Scarcella, A.; De Lucia, A.; Pasquariello, M. B.; Gambardella, P. :
Early death in two sisters with Hennekam syndrome. Am. J. Med. Genet. 93: 181-183, 2000.PubMed ID : 10925377
8. Van Balkom, I. D. C.; Alders, M.; Allanson, J.; Bellini, C.; Frank, U.; De Jong, G.; Kolbe, I.; Lacombe, D.; Rockson, S.; Rowe, P.; Wijburg, F.; Hennekam, R. C. M. :
Lymphedema-lymphangiectasia-mental retardation (Hennekam) syndrome: a review. Am. J. Med. Genet. 112: 412-421, 2002.PubMed ID : 12376947
9. Yasunaga, M.; Yamanaka, C.; Mayumi, M.; Momoi, T.; Mikawa, H. :
Protein-losing gastroenteropathy with facial anomaly and growth retardation: a mild case of Hennekam syndrome. Am. J. Med. Genet. 45: 477-480, 1993.

PubMed ID : 8465855