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Congenital pulmonary lymphangiectasia

General Information (adopted from Orphanet):

Synonyms, Signs:	PULMONARY CYSTIC LYMPHANGIECTASIS LYMPHANGIOMATOSIS, PULMONARY CPL Pulmonary lymphangiomatosis
Number of Symptoms	53
OrphanetNr:	2414
OMIM Id:	265300
ICD-10:	Q33.8
UMLs:	C0265800 C1849554
MeSH:	C537727
MedDRA:
Snomed:	45142002

Prevalence, inheritance and age of onset:

Prevalence:	> 100 cases [Orphanet]
Inheritance:	Autosomal recessive [Orphanet]
Age of onset:	Neonatal [Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases:

Genetic interstitial lung disease
-Rare genetic disease
Nonsyndromic respiratory or mediastinal malformation
-Rare developmental defect during embryogenesis
-Rare genetic disease
-Rare surgical thoracic disease
Primary interstitial lung disease specific to childhood due to alveolar vascular disorder
-Rare respiratory disease
Respiratory malformation
-Rare respiratory disease
Syndromic lymphedema
-Rare circulatory system disease
-Rare developmental defect during embryogenesis
-Rare genetic disease
-Rare skin disease

Symptom Information: Sort by abundance

	Symptom Information	Symptom	Abundance	DB Freq
1	(HPO:0000316)	Hypertelorism		644 / 7739
2	(HPO:0005280)	Depressed nasal bridge		381 / 7739
3	(HPO:0000272)	Malar flattening		277 / 7739
4	(HPO:0100540)	Palpebral edema		31 / 7739
5	(HPO:0000282)	Facial edema		5 / 7739
6	(HPO:0012368)	Flat face		106 / 7739
7	(HPO:0000431)	Wide nasal bridge		290 / 7739
8	(HPO:0000767)	Pectus excavatum		244 / 7739
9	(HPO:0001561)	Polyhydramnios		191 / 7739
10	(HPO:0001789)	Hydrops fetalis	Frequent [Orphanet]	63 / 7739
11	(HPO:0001790)	Nonimmune hydrops fetalis		15 / 7739
12	(HPO:0001541)	Ascites	Frequent [Orphanet]	94 / 7739
13	(HPO:0001744)	Splenomegaly	Occasional [Orphanet]	337 / 7739
14	(HPO:0012281)	Chylous ascites		2 / 7739
15	(HPO:0002240)	Hepatomegaly	Occasional [Orphanet]	467 / 7739
16	(HPO:0002577)	Abnormality of the stomach	Frequent [Orphanet]	84 / 7739
17	(HPO:0001530)	Mild postnatal growth retardation		7 / 7739
18	(HPO:0004325)	Decreased body weight	Frequent [Orphanet]	492 / 7739
19	(HPO:0001063)	Acrocyanosis	Very frequent [Orphanet]	56 / 7739
20	(HPO:0001702)	Abnormality of the tricuspid valve	Occasional [Orphanet]	32 / 7739
21	(HPO:0002092)	Pulmonary hypertension	Occasional [Orphanet]	109 / 7739
22	(HPO:0004414)	Abnormality of the pulmonary artery	Occasional [Orphanet]	50 / 7739
23	(HPO:0001635)	Congestive heart failure	Frequent [Orphanet]	232 / 7739
24	(HPO:0001697)	Abnormality of the pericardium	Frequent [Orphanet]	52 / 7739
25	(HPO:0010741)	Edema of the lower limbs		34 / 7739
26	(HPO:0002202)	Pleural effusion		22 / 7739
27	(HPO:0010310)	Chylothorax		6 / 7739
28	(HPO:0002102)	Pleuritis		7 / 7739
29	(HPO:0002205)	Recurrent respiratory infections		254 / 7739
30	(HPO:0006510)	Chronic obstructive pulmonary disease	Frequent [Orphanet]	19 / 7739
31	(HPO:0002093)	Respiratory insufficiency	Very frequent [Orphanet]	410 / 7739
32	(HPO:0006533)	Bronchodysplasia		1 / 7739
33	(HPO:0002103)	Abnormality of the pleura	Very frequent [Orphanet]	58 / 7739
34	(HPO:0006521)	Pulmonary lymphangiectasia		6 / 7739
35	(OMIM)	Growth retardation, mild		2 / 7739
36	(OMIM)	Lymphangitis, episodic		1 / 7739
37	(OMIM)	Edema reoccurs with infections		1 / 7739
38	(OMIM)	Edema of the face		1 / 7739
39	(OMIM)	Interstitial markings on x-ray		1 / 7739
40	(HPO:0011420)	Death	Very frequent [Orphanet]	184 / 7739
41	(OMIM)	Bone demineralization, diffuse		1 / 7739
42	(OMIM)	Normal intelligence		81 / 7739
43	(OMIM)	Pachypleuritis		1 / 7739
44	(OMIM)	Pleural effusions, chronic		1 / 7739
45	(OMIM)	Edema, subcutaneous, generalized		1 / 7739
46	(OMIM)	Pulmonary lymphangiectasia, congenital		1 / 7739
47	(OMIM)	Pleural membrane thickening		1 / 7739
48	([DEL]MedDRA:10011224)	Cough	Frequent [Orphanet]	70 / 7739
49	(HPO:0003828)	Variable expressivity		130 / 7739
50	(HPO:0000007)	Autosomal recessive inheritance		2538 / 7739
51	(HPO:0001522)	Death in infancy	Frequent [Orphanet]	275 / 7739
52	(OMIM)	Bronchodysplasia, mild		1 / 7739
53	(OMIM)	Edema is present at birth and then slowly decreases		1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol	Variation	Clinical significance	Reference

Additional Information:

Clinical Description OMIM

Frank and Piper (1959) described 2 unrelated infants with congenital pulmonary cystic lymphangiectasis. One was stillborn and the other lived only about 2 hours. In 1 patient there were similar lesions in the heart, pancreas, kidneys, and mesentery. ... Frank and Piper (1959) described 2 unrelated infants with congenital pulmonary cystic lymphangiectasis. One was stillborn and the other lived only about 2 hours. In 1 patient there were similar lesions in the heart, pancreas, kidneys, and mesentery. Scott-Emuakpor et al. (1981) described the disorder in 2 sisters who showed acute respiratory distress soon after birth and died in the neonatal period. Changes at autopsy were limited to the lungs. Moerman et al. (1993) reported on 7 perinatal autopsy cases of primary congenital pulmonary lymphangiectasis with bilateral chylothorax. They demonstrated that primary CPL is often complicated by chylous pleural effusions with ensuing pulmonary hypoplasia. Conversely, CPL appears to be a constant pathologic finding in spontaneous congenital chylothorax. These observations indicated a common pathogenesis for the 2 disorders. The authors suggested that the basic defect was not an intrinsic lung abnormality, but a developmental error of the lymphatic system resulting in a pulmonary lymphatic obstruction sequence. Njolstad et al. (1998) reported 3 sibs with nonimmune hydrops fetalis (236750), 2 of whom had histologic evidence of congenital pulmonary lymphangiectasia. One infant died at age 9 hours and another died in utero. Postmortem findings included subcutaneous edema, ascites, hydrothorax, and pleural effusions. The surviving child had frequent upper airway infections with simultaneously increasing edema of the arms and face. She had normal neurologic development. Njolstad et al. (1998) concluded that the nonimmune hydrops fetalis was secondary to primary pulmonary lymphangiectasia, and suggested an underlying genetic cause in this family. Jacquemont et al. (2000) reported 3 French sibs and an unrelated girl with CPL. Nonimmune hydrops fetalis was observed in 3 patients, and was fatal in 1. Other variable prenatal findings included polyhydramnios and chylothorax. The main clinical features were facial and lower limb edema, episodic lymphangitis, and pleural effusions. One patient also had bilateral chylothorax. Chest radiographs showed chronic pleural effusions, pachypleuritis, and interstitial markings. Pulmonary biopsy of 1 patient showed signs of bronchodysplasia and lymph vessel ectasia. Other common features included mild growth retardation, hypertelorism, palpebral edema, flat nasal bridge, diffuse bone demineralization, and normal intelligence. Although histologic diagnosis of pulmonary lymphangiectasia had been noted by Njolstad et al. (1998) to be uncertain, Jacquemont et al. (2000) stated that chylothorax, chronic pleural effusions, and pleural membrane thickening were consistent with pulmonary lymphangiectasia, especially in the presence of normal cardiac findings. Jacquemont et al. (2000) noted the resemblance to Hennekam syndrome (235510), but concluded that their cases and the cases reported by Njolstad et al. (1998) represented a distinct nosologic entity. Stevenson et al. (2006) reported 2 sibs with congenital nonimmune hydrops, pleural effusions, and chylothorax. One sib had histologically confirmed pulmonary lymphangiectasia. Both sibs died in the neonatal period. Stevenson et al. (2006) suggested that disordered lymphatic drainage was the basic defect leading to a secondary condition of CPL.

Symptoms & Signs

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	Disease
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