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Hennekam syndrome is characterised by the association of lymphoedema, intestinal lymphangiectasia, intellectual deficit and facial dysmorphism.
ORPHA:2136Classification level: Disorder
The prevalence is unknown but less than 50 cases have been reported in the literature. The entity occurs in all ethnic groups.
Lymphoedema is usually present at birth or appears during early infancy. It generally becomes severe within a few years, affecting mainly the face, lower limbs and genitalia, and often leads to complications such as erysipelas. Intestinal lymphangiectasia may result in protein-losing enteropathy, mild growth retardation, peripheral oedema and ascites. The degree of intellectual deficit is highly variable, even within a single family. Facial symptoms are characterised by a flat face, a broad and depressed nasal bridge, hypertelorism, epicanthal folds, a small mouth, and low-set ears with a narrow meatus. Delayed puberty, tooth anomalies, gingival hypertrophy, seizures, blood vessel anomalies, congenital pulmonary lymphangectasia, and a narrow upper throrax have also been reported. Less common manifestations include glaucoma, nonimmune hydrops fetalis, chylothorax, brain cysts, and craniosynostosis.
The aetiology remains unknown but the clinical manifestations suggest that the syndrome results from defects in the mechanism of fluid uptake due to abnormal vascular and lymphatic development.
The diagnosis is suspected on the basis of the clinical phenotype. Intestinal lymphangiectasia may be suspected from biological studies revealing hypogammaglobulinemia, hypoalbuminemia, lymphopenia and increased alpha-1 antitrypsin excretion in the faeces, and can be confirmed by duodenal biopsy. However, several biopsies are often needed before lymphangiectasia can be shown. Lymphatic impairment can be evaluated by radionuclide lymphoscintigraphy.
The differential diagnosis should include other rare syndromes associated with congenital lymphoedema such ascholestasis-lymphoedema syndrome, as well as Noonan syndrome (see these terms).
The syndrome is transmitted as an autosomal recessive trait.
Management and treatment
Treatment is symptomatic with many patients requiring total parenteral nutrition with a medium-chain triglyceride-rich diet and albumin infusions. Vitamin and electrolyte supplements together with a high-protein diet have been reported to be of benefit. Pulmonary lymphangiectasia is especially difficult to treat and can be relentlessly progressive in adulthood. The lymphoedema may be severely disabling and require repeated surgical intervention.
The prognosis is variable and a few patients have been described with very severe manifestations leading to early death.