Hennekam syndrome: a rare and often ignored cause of intestinal lymphangiectasia
28 May 2014 (online)
One other rare cause of intestinal lymphangiectasia is Hennekam syndrome .
Hennekam syndrome is typically characterized by the presence of intestinal lymphangiectasia, mental retardation, and characteristic facial anomalies . It is an autosomal recessive disorder, and consanguinity has been noted as a major contributing factor in transmission of the trait. In addition to the bowels, the lymphangiectasia may develop in renal tissue and endocrine glands such as the thyroid. A number of associated rare features may be seen in some patients. For example, Angle et al. have recently reported rectal prolapse as well as vesicoureteral reflux in a female patient with Hennekam syndrome .
Most individuals with Hennekam syndrome have characteristic facial abnormalities, such as a flat face with accompanying puffy eyelids and hypertelorism ; the nasal bridge is typically flat and the ears are typically small. Congenital extremity and genital lymphedema is present in most patients. Preputial hyperplasia is another characteristic feature, and severe phimosis may be seen in some patients . Rarely, cardiac anomalies may develop; Nisli et al. reported pericardial effusion in a patient with Hennekam syndrome, and abnormal pulmonary venous drainage has also been reported . The skin may also be affected, resulting in the formation of verrucous papules, plaques, and pseudovesicular cutaneous lesions. Erysipelas infection is commonly seen in patients with Hennekam syndrome. Palmar creases may also be seen. Nonimmune hydrops fetalis may develop in newborns . Interestingly, newborns with Hennekam syndrome may present with respiratory distress due to a myriad of reasons. Bellini et al. reported on a newborn with pulmonary lymphangiectasia and chylothorax, resulting in respiratory difficulty .
Hematological examination reveals moderate-to-severe iron deficiency anemia. Blood assays reveal attenuated albumin levels. Genetic analysis reveals typical CCBE1 mutations . Lymphangiectasia of the small bowel can be delineated clearly on lymphangiography. Lymphedema of the extremities may also be evident on lymphangiography. Computed tomography imaging may reveal a number of other intra-abdominal anomalies, such as polysplenia and median hepatic location , and ectopic kidneys have also been noted. Intestinal biopsies reveal the typical lymphangiectasia. Fecal examination may reveal accentuated alpha-1 antitrypsin levels. Magnetic resonance imaging of the brain may reveal subcortical hyperintensity lesions , and craniosynostosis has also been reported.
Albumin infusions may be needed in patients with Hennekam syndrome. A medium-chain triglyceride-rich diet is necessary in most patients. Al Sinani et al. reported success with octreotide therapy in minimizing intestinal protein loss and the subsequent hypoalbuminemia .
As is clear from the above discussion, Hennekam syndrome is a rare cause of intestinal lymphangiectasia. It should be considered a definite possibility during the differential diagnosis of patients with intestinal lymphangiectasia and concurrent lymphedema who have the abovementioned facial anomalies.
- 1 Ersoy O, Akin E, Demirezer A et al. Evaluation of primary intestinal lymphangiectasia by capsule endoscopy. Endoscopy 2013; 45: E61-62
- 2 Forzano F, Faravelli F, Loy A et al. Severe lymphedema, intestinal lymphangiectasia, seizures and mild mental retardation: further case of Hennekam syndrome with a severe phenotype. Am J Med Genet 2002; 111: 68-70
- 3 Angle B, Hersh JH. Expansion of the phenotype in Hennekam syndrome: a case with new manifestations. Am J Med Genet 1997; 71: 211-214
- 4 Erkan T, Kutlu T, Cullu F et al. Hennekam syndrome. Arch Pediatr 1998; 5: 1344-1346
- 5 Cormier-Daire V, Lyonnet S, Lehnert A et al. Craniosynostosis and kidney malformation in a case of Hennekam syndrome. Am J Med Genet 1995; 57: 66-68
- 6 Nisli K, Oner N, Kayserili H et al. A case of Hennekam syndrome presenting with massive pericardial effusion. Turk Kardiyol Dern Ars 2008; 36: 325-328
- 7 Musumeci ML, Nasca MR, De Pasquale R et al. Cutaneous manifestations and massive genital involvement in Hennekam syndrome. Pediatr Dermatol 2006; 23: 239-242
- 8 Bellini C, Mazzella M, Arioni C et al. Hennekam syndrome presenting as nonimmune hydrops fetalis, congenital chylothorax, and congenital pulmonary lymphangiectasia. Am J Med Genet A 2003; 120A: 92-96
- 9 Rockson SG, de los Santos M, Szuba A. Lymphoscintigraphic manifestations of Hennekam syndrome – a case report. Angiology 1999; 50: 1017-1020
- 10 Al-Gazali LI, Hertecant J, Ahmed R et al. Further delineation of Hennekam syndrome. Clin Dysmorphol 2003; 12: 227-232
- 11 Huppke P, Christen HJ, Sattler B et al. Two brothers with Hennekam syndrome and cerebral abnormalities. Clin Dysmorphol 2000; 9: 21-24
- 12 Al Sinani S, Rawahi YA, Abdoon H. Octreotide in Hennekam syndrome-associated intestinal lymphangiectasia. World J Gastroenterol 2012; 18: 6333-6337