BN
Akyildiz1, N Urganci2, H Kayserili3, RO Rosi3
1 Department of Paediatric Intensive Care, Erciyes University Medical Faculty, Kayseri, Turkey
2 Division of Paediatric Gastroenterology, Clinic of Pediatrics, Sisli Etfal Hospital, Istanbul, Turkey
3 Medical Genetics Department, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey
Corresponding author: Başak Nur Akyıldız
Erciyes University Medical Faculty Department of Intensive Care, Kayseri/ Turkey
e-mail: basaknurbesra@gmail.com
SMJ 2009 54(3): 58
Abstract
We report a patient presenting with an abdominal distention and irritiability, who was found to have Hennekam syndrome. A physical examination revealed left sided hemihypertrophy and a mass with undefined margins around the umblical region. Ultrasonography and contrast enhanced computerised tomography revealed a solid heterogeneous mass extending from the parapancreatic region into the mesenteric root and, diagnostic laparotomy was performed. The intestinal walls and the mesentery were found to be diffusely thickened. Histopathological analysis revealed fibrosis along with cystic enlargement of the lymphatic vessels. The patient had left periorbital edema and facial dysmorphism. Non-pitting edema of the abdomen, left arm, left leg, and left labia majora was noted. Laboratory tests showed hypoproteinemia, hypoalbuminemia, and high faecal α-1 anti trypsin. Endoscopic examination revealed milky fluid oozing from the mucosa into the duodenal lumen. Histopathological analysis revealed total villus atrophy and cryptic hyperplasia. We postulate that an enlargement in the intestinal wall could be mistaken for an abdominal mass, and, we present this case of an abdominal mass as a new manifestation of Hennekam syndrome.
Key words: abdominal mass, Hennekam syndrome
Introduction:
First described in 1989,1 Hennekam syndrome is an autosomal recessive disorder characterised by intestinal lymphangiectasia with severe lymphodema of the limbs, genitalia and face complicated with mental retardation and facial dysmorphism. There have been 38 cases of Hennekam syndrome presented in the literature.2-17 We report a case of Hennekam syndrome presenting as an abdominal mass, which has not been previously described in the literature.
Case Presentation:
A 2-month-old female presented to our paediatric surgery clinic with abdominal distention and irritability. The patient was born by caesarean section due to post-maturity. Both antenatal and family history were uneventful. A physical examination revealed on the left-sided hemihypertrophy, abdominal distension and a mass around the umblical region with undefined margins. The results of the laboratory tests were as follows: haemoglobin - 110 g/L, white cell count - 9.9 x 109/L, platelets – 381 x 109/L, alpha-feto protein - 2.51 µg/L ( N:<10 µg/L), neuron specific enolase: 4.8 ng/mL (N: < 20 ng/mL) in blood and vanyl mandalic acid: 4.8 mg/24 h urine collection (N: 2-10 mg/24 h urine collection). An ultrasonography and contrast–enhanced CT revealed a solid heterogeneous mass (6 x 5 x 3.5cm) extending from the parapancreatical region into the mesenteric root. No congenital abnormalities of the kidneys, liver, pancreas and spleen were detected. A diagnostic laparatomy was performed, which revealed that the intestinal walls and the mesentery were diffusely thickened. Approximately 200 ml of chylous ascites was present. A histopathological examination of biopsies from the ileal and colonic mesentery revealed fibrosis along with cystic enlargement of the lymphatic vessels. These findings were considered to be compatible with intestinal lymphangiectasia and the patient was referred to the paediatric gastroenterology division for further follow-up.
In the pediatric gastroenterology clinic, on the physical examination at two months of age; both the patient’s weight (4600 g) and head circumference (38 cm) were at the 25th percentiles and her height (53.5 cm) was between the 10th and 25th percentiles. She had left periorbital oedema, epicanthic folds, hypertelorism, a depressed nasal root, anteverted nares, high palate and helical anomaly of the left ear. Non-pitting oedema of the abdomen, left arm, left leg and left labia majora was noted. Cardiology and respiratory examinations were normal and no organomegaly were present. Tonus was normal with the exception of hypoactive reflexes on the left side. Laboratory tests showed that total protein at 41g/L (61-79 g/L), albumin at 17 g/L (18-30 g/L), IgG at 2.85 g/L (1.72-10.69 g/L), Ig A at 0.32 g/L (0.11-1.06 g/L), IgM at 0.39 g/L (0.41-1.73 g/L), and faecal α-1 anti trypsin at 350 mg/day (0-100 mg/day). Endoscopic examination revealed oozing of milky fluid from the mucosa into the duodenal lumen. Histopathological examination revealed total villus atrophy and an inflammatory reaction in the lamina propria. The patient was lost to follow up in his period. She admitted again with more severe symtoms at 18 months. The presence of lymphoedema, facial dysmorphism and intestinal lymphangiectasia led to a clinical diagnosis of Hennekam when the baby was 18 months. The patient was given human albumin 1 gr/kg/day, and a formula rich in medium chain fatty acids was added to her diet. At further follow-up, the Denver Developmental test was administered at 18 months of age and revealed normal results for social, language skills, Fine motor skills were normal at the right side but abnormal on the left ( 9 months development level), and gross motor skills were also delayed (10 months development level). The karyotype was 46,XX; normal. The patient did not return to clinic after given treatment and was lost to follow-up. The patient died at aged three years
from sepsis.
Discussion:
Hennekam syndrome is a rare disorder characterised by intestinal lymphangiectasia, lymphoedema, various facial anomalies and mental retardation.1 Generalised developmental defects in the lymphathic system are characteristic of the syndrome. It is common for the involvement of the intestines, extremities and genital region although pleura, pericardium, thyroid gland, and kidneys are affected less frequently.15 The facial anomalies characteristic of Hennekam Syndrome include a flat midface, a flat nasal bridge, hypertelorism, epicanthic folds, smooth philtrum, a small mouth with a variable degree of gingival hypertrophy, and low set mildly dysplastic ears. The facial anomalies are typical of congenital lymphoedema occurring during the early stages of gestation. These facial anomolies have been attibuted to the lymphatic obstruction, which affects the early migration of neural crest tissue.3, 15 In our case, hypertelorism, eyelid oedema, epicanthic folds, depressed nasal root, small mouth, and low-set ears were found.
Autosomal recessive syndromes should be considered in the differential diagnosis presenting with lymphoedema and/or lymphangiectasia. Aagenaes syndrome (MIM % 214900)18 differs from Hennekam syndrome, as the patient has hereditary recurrent cholestasis, jaundice, cirrhosis and fibrosis of the liver tissue in later childhood. Also, the facial dysmorphisms which are characteristic of Hennekam syndrome are absent in Aagenaes syndrome. Urioste syndrome (MIM % 235255)19, along with lymphangiectasia, shows persistence of mullerian derivatives and other congenital anomalies including post-axial polydactyly, redundant nuchal skin, and renal anomalies. These characteristics excluded this entity from our differential diagnostic list. Autosomal recessive congenital lymphoedema (MIM % 247440)20 has no associated malformations making it a distinct syndrome. Congenital chylothorax syndrome (MIM % 603523)21, with congenital pulmonary lymphangiectasis and bilateral chylothorax, also has no associated malformations other than a reported case complicated by congenital pyloric stenosis22; thus excluding this syndrome from our differential diagnosis.
Protein
loss and malabsorption due to intestinal lymphangiectasia, another typical
characteristic of Hennekam syndrome, causes hypoproteinemia, hypoalbuminemia,
lymphopenia, recurrent infections, and growth retardation.16 In our
case, enlargement of the intestinal wall was considered to be indicative of
intestinal lymphangiectasia. This finding could mimic an abdominal mass and
mislead a physician. In Hennekam syndrome, individuals are usually normal at
birth and growth retardation manifests postnatally. Yasunaga et al3
reported that protein loss due to intestinal lymphangiectasia is compensated for
by maternal support during the intrauterine phase and thus growth retardation
occurs later. The birth weight, height and head circumference of our patient
were within normal ranges at two months and no growth delay was observed at nine
months of age.
Whilst it is commonly the intestinal system, extremities, face and genital organs involved in Hennekam Syndrome, other problems have been reported. Other cases have included ectopic kidney and coronal synotosis,4 congenital heart disease,5 unilateral stenosis with hydronephrosis.15 We did not detect any additional anomalies in our patient.
Of the 38 cases reported so far; 15 described varying degrees of mental deficiences.1,2,4-6,11,14,15. Our patient did not show severe psychomotor deficiencies except for gross motor skills.
Treatment is symptomatic in Hennekam syndrome, as in other conditions with protein-losing enteropathy. In these cases, albumin infusion, restricted fat intake to decrease lymphathic flow, and special diet formulas including medium chain fatty acids are used since they directly enter the circulation.23 Our patient was administered albumin 1 g/kg/d at the time of admission and a formula rich in medium chain fatty acids was added in addition to her diet of breast milk. Despite the improved clinical picture, the patient was lost to follow-up and later it was found that she had died due to sepsis when she was three years old.
Since enlargement of the intestinal wall can be mistaken for an abdominal mass, we recommend that Hennekam syndrome should be considered in the differential diagnosis of patients presenting with abdominal masses who have accompanying facial dysmorphism and/or lymphoedema.
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