In other species: dog , horse

Categories: Immune system phene

Single-gene trait/disorder: unknown

Disease-related: yes

Cross-species summary: Lymphedema

Species-specific name: Inherited (congenital) lymphedema

Species-specific description: Inherited primary lymphoedema has been reported in several breeds including Ayrshire, Hereford and Japanese black cattle (Donald et al., 1952; Morris et al., 1954; Schild et al., 1991; Yamaguchi et al., 1995). A defect of the lymphatic system causes chronic oedema, particularly of the extremities and hindlimbs. In Hereford cattle the lower limbs and extremities appear to be most affected in a clinical presentation similar to that observed in humans with heritable lymphatic malformations (Schild et al., 1991). Affected cattle appear highly susceptible to secondary diseases, have a reduced life expectancy, and show abnormal lymph node anatomy on histopathology (Schild et al., 1991). Clinical presentation in Ayrshire cattle is distinct, with a severe and mild form of the disease described (Donald et al., 1952). For the severe form see: OMIA:000493-9913 : Hydrops foetalis.  Yamaguchi et al. (1995) report a 9 month old Japanese Black calf with congenital lymphoedema.  (IT thanks Alexandra Fraser for suggested changes to this entry (31/01/2025))

Inheritance: Schild et al. (1991) report variable expressivity and incomplete penetrance in Hereford cattle, based on disease expression following test matings: 14.28% of offspring were affected when a carrier Hereford bull was mated to unrelated Charolais females, and 18.18% were affected when the same bull was mated to his daughters. 

Clinical features: In Ayrshire cattle, two clinical presentations have been reported. The generalised form results in oedema affecting the entire body (see: OMIA:000493-9913 : Hydrops foetalis), whilst the milder form predominantly affects the head, neck, limbs, and tail (Donald et al., 1952; Morris et al., 1954). Morris et al. (1954) report findings relating to two Ayrshire calves with the milder form. Both calves were oedamatous at birth and were investigated at the age of 5 weeks and 10 days due to oedema of the head and limbs.
In Hereford cattle, swelling of limbs (largely hindlimbs and occasionally forelimbs), tail, prepuce, and (in one individual) the head, were observed in calves either immediately or several months after birth (Schild et al., 2019) . In areas of oedema the skin appeared thickened, and transverse fissures were observed on swollen areas of the hindlimbs. The skin in these fissures was ulcerated and occasionally associated with secondary myiasis or necrosis. The muscle underlying areas of oedema were abnormally firm, pale, and oedematous. Translucent oedema was found in the subcutaneous tissue of affected areas ((Schild et al., 2019).
Yamaguchi et al. (1995) investigated a "9-month-old male Japanese Black calf with subcutaneous edema in mainly both limbs ... ." 

Pathology: Morris et al. (1954) report developmental abnormalities in the lymphatic system in two affected Ayrshire calves.
Schild et al. (2019) summarises pathological findings in Hereford cattle. Prescapular and iliofemoral lymph nodes were smaller in affected animals than in control animals. Popliteal lymph nodes were bi- or uni-laterally absent in a number of animals and, when present, were also smaller than the controls. Similarly, superficial lymphatic vessels were absent in a number of affected individuals. Absence of vessels presumably due to elevated lymphatic pressure caused by lymphatic hypoplasia. Lesions were detected on the peripheral and mesenteric lymph nodes of affected animals using histopathology. These lesions showed hypoplastic changes leading to sclerosis of the lymphatic sinuses. In addition, oedema of the subcapsular and medullar sinuses of affected lymph nodes was noted. The affected lymph nodes appeared hypocellular. No significant abnormalities detected on other organs.
Yamaguchi et al. (1995): "Necropsy [of the affected Japanese Black animal] revealed about 20 l of ascites and severe edema in the large omentum, abomasal folds, conjunctiva and rectum. Only small internal iliac and hepatic lymph nodes were found. Histopathology revealed lymph node dysplasia showing excess trabecular formation, reticular cell proliferation, and obvious dilation of both afferent and efferent lymphatics. "

Breeds: Ayrshire (Cattle) (VBO_0000120), Hereford (Cattle) (VBO_0000232), Japanese Black, Japan (Cattle) (VBO_0004987).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).