Paediatric chylous ascites in tropics is commonly caused by infections and trauma. We describe the clinical characteristics of an uncommon inherited cause of chylous ascites, Hennekam syndrome, treated by nutritional modification.
- congenital disorders
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Syndromic causes of lymphoedema are under-recognised and often missed. We describe a patient with Hennekam syndrome whom we had diagnosed on the basis of characteristic dysmorphism, intestinal lymphangiectasia and chylous ascites. Early recognition and supportive therapy improve quality of life in patients. This also prevents them from undergoing unwanted investigations or empirical therapies.
An 8-year-old boy presented with a history of bilateral progressive pedal oedema since 5 months of age. He was noted to have progressive abdominal distension since past 1 month, compelling his parents to seek medical opinion. On further exploration of history, he had focal seizures since early infancy warranting antiepileptic therapy. The child had global developmental delay with absent neck holding, unidextrous grasp, social smile and monosyllabic speech. There was no history of chronic diarrhoea, stigma of liver disease, urinary or cardiac complaints. Family history was unremarkable. On examination, the child was undernourished with a weight of 15 kg (−5.7 Z), length of 97 cm (−6 Z), Occipito frontal circumference of 44 cm (−6.8 Z). Physical examination revealed generalised extensor posture (figure 1A), and dysmorphism which included flattened face, puffy eyelids, abnormal dentition with carious teeth with hypertrophied gums (figure 1B), depressed nasal bridge, short stout fingers with camptodactyly (figure 1C) and bilateral non- pitting oedema. Abdomen was grossly distended, and there was no organomegaly but fluid thrill was present. He had generalised sarcopenia and deep tendon reflexes were absent.
The child had mild normocytic normochromic anaemia (haemoglobin 103 g/L) with normal electrolyte profile and liver function. Ultrasound abdomen showed gross ascites. Diagnostic paracentesis revealed a milky white fluid suggestive of chylous ascites (triglycerides: 1008 mg/dL), cells 280/μL with 90% lymphocytes, protein 3.9 g/dL (high protein: >2.5 g/dL), low serumascites albumin gradient (SAAG) 0.7 g/dL (non-portal hypertensive) with a normal adenosine deaminase (ADA) (8 IU/L) and no malignant cells. MR lymphangiogram was normal. Upper gastrointestinal endoscopy revealed whitish blebs in duodenum and biopsy was suggestive of lymphangiectasia (figure 2A,B). MRI brain was normal.
Intestinal lymhangiectasia is an important cause of protein-losing enteropathy and is usually secondary to infections like abdominal tuberculosis and filariasis in a tropical country like ours. The other causes are abdominal trauma, lymphatic tumours or a surgical sequelae. However, it can also be caused by genetic syndromes causing lymphatic malformations, for example, Turner, Noonan, Klippel Trenauny and Hennekam syndromes. We made a diagnosis of Hennekam syndrome in our patient as he had intestinal lymphangiectasia, characteristic facial and dental anomalies and neurodevelopmental abnormality along with chylous ascites and lymphoedema.
The child was given nutritional rehabilitation and fat-restricted medium-chain triglyceride (MCT) (coconut oil/commercial MCT)-rich diet and intravenous albumin. The abdominal distension started subsiding. Patient was discharged with nutritional advice, supplements and physiotherapy exercises.
Outcome and follow-up
On regular follow-up till 6 months, patient had complete resolution of ascites and reduced extremity oedema. However after a span of 3 months after his outpatient visit, the child died due to an acute event of aspiration pneumonia, possibly secondary to seizures.
Hennekam syndrome is to be considered in patients with chylous ascites and lymphangiectasia, when it is associated with mental retardation, facial dysmorphism, peripheral lymphoedema and seizures. It was first described in a Dutch family and the inheritance is autosomal recessive.1 Spectrum of presentation ranges from very mild to life-threatening illness and hence ample number of cases may remain unrecognised. The causative mutation is seen in CCBE1 or PROX1 gene.2 3 The most commonly seen mutations causing defective vasculogenesis of lymphatics are involving vascular endothelial growth factor 3 (VEGF-3/VEGFR) signalling pathways.4
The most common sites involved are extremities and intestines, but these are not seen universally.5 Involvement of the pleura and pericardium leads to symptomatic effusions.6 The lymphoedema is seen soon after birth and can be asymmetric. This can predispose to erysipelas and cellulitis. The hallmark symptoms of intestinal lymphangiectasia are attributed to protein-losing enteropathy, hypogammaglobulinaemia, loss of fat-soluble vitamins and increased predisposition to food allergies. Generalised lymphatic malformation leads to chylous ascites (triglyceride levels >200 mg/dL and lymphocytic predominant ascites). These patients usually have a varying spectrum of mental retardation and seizures are known in one in three of these patients. Defective dural lymphatics cause seizures and developmental delay. Dysmorphism is striking, which includes flat face, hypertelorism, depressed nasal bridge, low set ears, dysplastic ears, gingival hypertrophy and high arched palate.7 Facial anomalies are due to the intrauterine lymphoedema. Dental anomalies include supernumerary molars, microdontia peg-shaped incisors and high predisposition to dental caries. Growth retardation is well described. Digital anomalies include syndactyly and camptodactyly (claw hands).7 Upper thorax is narrow and pectus excavatum is also seen. Renal lymphangiectasia leading to end-stage renal disease is known. Conductive hearing loss and glaucoma are rare manifestations.
Our patient with peripheral lymphoedema, chylous ascites, lymphangiectasia, facial dysmorphism, dental anomalies, developmental delay, growth retardation and seizures fits into the profile of Hennekam syndrome. He was managed with nutritional rehabilitation to which his anasarca responded brilliantly.
The prognosis varies depending on the clinical phenotype. Important causes of death in these patients include sepsis secondary to cellulitis or erysipelas and acute life-threatening events like seizures or aspiration pneumonia. Our case report highlights the typical clinical profile of Hennekam syndrome, benefits of its early recognition and timely therapeutic interventions, in a setting where it is more common to encounter tropical causes of chylous ascites like infections.
Chylous ascites can be secondary to genetically inherited causes apart from trauma and tuberculosis which are the most common causes in developing countries.
Hennekam syndrome should be suspected when chylous ascites coexists with facial dysmorphism, intestinal lymphangiectasia and developmental delay.
Early diagnosis with supportive management including dietary modification improves the quality of life in these patients.
Prognosis is guarded; death can be secondary to aspiration pneumonia due to the neurological sequelae, as seen in our case.
Contributors JM managed the case, wrote the manuscript and did the upper gastrointestinal endoscopy. VV was involved in managing the patient. BT did the histopathological examination. SBL finalised the manuscript and will act as the guarantor of the paper.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
Patient consent for publication Parental/guardian consent obtained.
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