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Lymphedema - atrial septal defects - facial changes

General Information (adopted from Orphanet):

Synonyms, Signs:	LYMPHEDEMA, ATRIAL SEPTAL DEFECT, AND CHARACTERISTIC FACIES irons-bianchi syndrome
Number of Symptoms	26
OrphanetNr:	86915
OMIM Id:	601927
ICD-10:	Q87.8
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence:	3 cases [Orphanet]
Inheritance:	Autosomal recessive [Orphanet]
Age of onset:	Neonatal Infancy [Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases:

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	DB Freq
1	(HPO:0000034)	Hydrocele testis	18 / 7739
2	(HPO:0100673)	Vaginal hydrocele	8 / 7739
3	(HPO:0000311)	Round face	104 / 7739
4	(HPO:0011220)	Prominent forehead	137 / 7739
5	(HPO:0000348)	High forehead	157 / 7739
6	(HPO:0000286)	Epicanthus	371 / 7739
7	(HPO:0000455)	Broad nasal tip	67 / 7739
8	(HPO:0000582)	Upslanted palpebral fissure	185 / 7739
9	(HPO:0000219)	Thin upper lip vermilion	112 / 7739
10	(HPO:0000506)	Telecanthus	156 / 7739
11	(HPO:0005280)	Depressed nasal bridge	381 / 7739
12	(HPO:0000750)	Delayed speech and language development	197 / 7739
13	(HPO:0001562)	Oligohydramnios	75 / 7739
14	(HPO:0005099)	Severe hydrops fetalis	2 / 7739
15	(HPO:0001539)	Omphalocele	102 / 7739
16	(HPO:0001597)	Abnormality of the nail	115 / 7739
17	(HPO:0002623)	Overriding aorta	8 / 7739
18	(HPO:0001629)	Ventricular septal defect	316 / 7739
19	(HPO:0004749)	Atrial flutter	20 / 7739
20	(HPO:0001643)	Patent ductus arteriosus	228 / 7739
21	(HPO:0010775)	Vascular ring	3 / 7739
22	(HPO:0001631)	Atria septal defect	274 / 7739
23	(HPO:0001004)	Lymphedema	62 / 7739
24	(OMIM)	Horizontal chin cleft	1 / 7739
25	(HPO:0000007)	Autosomal recessive inheritance	2538 / 7739
26	(OMIM)	Short, deep-set toenails	1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol	Variation	Clinical significance	Reference

Additional Information:

Clinical Description OMIM

Irons et al. (1996) reported 2 brothers with lymphedema of the lower limbs, hydrocele, atrial septal defects (ASD), epicanthus, and wide nasal bridge. Their stillborn sister, who was born after a pregnancy complicated by preeclampsia, had severe hydrops ... Irons et al. (1996) reported 2 brothers with lymphedema of the lower limbs, hydrocele, atrial septal defects (ASD), epicanthus, and wide nasal bridge. Their stillborn sister, who was born after a pregnancy complicated by preeclampsia, had severe hydrops fetalis, omphalocele, ASD, and polysplenia. The family history was unremarkable. Irons et al. (1996) considered this complex to be a previously unknown syndrome with autosomal recessive inheritance. Van Steensel et al. (2007) described a 3-year-old Dutch girl with features similar to those in the patients reported by Irons et al. (1996). She was born prematurely at 35 weeks with a dizygotic twin sister. The parents were nonconsanguineous and 3 sibs were healthy. During pregnancy, fetal hydrops was detected from weeks 16 to 20. At birth, she was noted to have bilateral swelling of the lower legs consistent with lymphedema. She also had atrial flutter, a large perimembranous ventricular septal defect with significant left/right shunting, a secundum type atrial septal defect type II, and an overriding aorta with vascular ring. At age 2 months, the ventricular septal defect was closed, the vascular ring corrected, and an aortopexia was performed. Progressive bilateral lower leg lymphedema was noted at 3 years of age. Physical examination at that time revealed nonpitting edema of the toes, feet, and lower legs. Her face showed epicanthal folds, flat nasal bridge with telecanthus, and a high forehead. Lymphoscintigraphy revealed complete absence of lymph drainage in both lower legs. Karyotype was normal 46,XX, and a 22q11 deletion was excluded by FISH. Analysis of several genes known to be involved in syndromes with lymphedema detected no pathogenic mutations. Levine and Echiverri (2009) reported a 22-year-old African American man with mild mental retardation, mild dysmorphic features, history of a congenital atrial septal defect, massive lymphedema of the lower limbs, and hydrocele. Dysmorphic features included prominent forehead, bitemporal narrowing, epicanthal folds, hypertelorism, and flat and wide nasal bridge. Levine and Echiverri (2009) noted that the patient resembled the brothers reported by Irons et al. (1996), although their patient did not have deep-set nails or a horizontal chin cleft, and had more severe cognitive impairment.

Symptoms & Signs

	Field	Query
	Disease
	Symptom