Agenesis of the inferior vena cava in nail-patella syndrome
(Portuguese PDF version)

Simone Castelo Branco Fortaleza,1 André Pires Cortez,2 Luís Edmundo Teixeira Arruda Furtado,2 João Sales Pimentel,3 Manoel Pedro Guedes Guimarães,4 Antonio Luiz Carneiro Jerônimo,4 José Otho Leal Nogueira,5 José Walter Correia6

1. Resident Physician, Hospital Geral Dr. César Cals, Fortaleza, CE, Brazil.
2. Intern, Hospital Geral Dr. César Cals, Fortaleza, CE, Brazil.
3. Vascular Surgeon, Hospital Geral Dr. César Cals, Fortaleza, CE, Brazil.
4. Preceptor, Medical Clinic Service, Hospital Geral Dr. César Cals, Fortaleza, CE, Brazil.
5. Professor, School of Medicine, Universidade Federal do Ceará (UFC), Fortaleza, CE, Brazil.
6. Head of the Medical Clinic Service, Hospital Geral Dr. César Cals, Fortaleza, CE, Brazil

Correspondence:
Antonio Luiz Carneiro Jerônimo
Rua Tenente Benévolo, 2211/1002
CEP 60160-041 - Fortaleza, Ceará
Brazil
Tel.: +55 (85) 264.2627
Fax: +55 (85) 221.6438
E-mail: jeronimo@fortalnet.com.br

ABSTRACT

The authors report on the case of a 23-year-old girl, with the complete form of nail-patella syndrome, a rare disorder inherited as an autosomal dominant trait. Besides the classical physical symptoms of the syndrome, the patient presented portal hypertension signs, manifested by large-volume ascites, with exuberant collateral circulation observed in both abdominal and thoracic wall, and esophagus varices without evidences of associated liver disease. Surprisingly, the computed tomography of the abdomen demonstrated the complete absence of the inferior vena cava, confirmed by venography. This is the first case in the literature describing nail-patella syndrome associated with agenesis of inferior vena cava.

Key-words: syndrome, inferior vena cava, portal hypertension.
Palavras-chave: síndrome, veia cava inferior, hipertensão portal.

J Vasc Br 2004;3(3):273-6

The nail-patella syndrome (NPS), otherwise known as hereditary Onychoosteodysplasia, Iliac Horn syndrome, Fongs disease and Turner Kieser Syndrome, was first reported by Chatelain in 1820.^1-5 It is a rare autosomal dominant condition with high penetrance and its symptoms may vary widely from case to case. Classically, patients have a classical tetrad of pathologic symptoms including absent or hypoplastic patella, fingernail dysplasia, bony processes along the posterior surfaces of the iliac bones, also called iliac horns, and elbow abnormalities, including head of radius dislocation.

The incidence of NPS is 4.5 per million population in the United States, whilst in England it is 22 per million inhabitants.^6-8 It is caused by mutation in the LMX1B gene located on the long arm of chromosome 9q34,^9-11 and in 10% of cases, NPS is in the same chromosome that carries information of the ABO^8,11,12 blood group.

CASE REPORTS

M.L.N.L., female, 23 years-old, entered the Hospital Geral César Cals (HGCC), in Fortaleza, Brazil, in 1996, with anasarca in the last 9 previous months, foamy urine, menstrual changes, pain and increased abdominal volume. She was born preterm (7 months of pregnancy), with congenital malformation and delayed motor development, however, she did not present psychological deficit. There were not reports of similar cases in her family, except a maternal uncle with isolated nail alterations.

The physical examination revealed bilateral convergent strabismus, left eyelid ptosis, anomalous implanted ears, long nose with prominent nasal septum, fingernail beds dystrophy, bilateral cubital pterygium (Figure 1), absence of patellas, rigidity of knees, bilateral prominence of the calcaneum, flat feet and large-volume ascites with increased collateral circulation, umbilical hernia and lower limb edema.

Figure 1 - Cubital pterygium.

Laboratory tests identified anemia (hematocrit = 32%, hemoglobin = 10.6g/dl), hypoalbuminemia (2.6 g/dl), hypercholesterolemia (373 mg/dl), high 24-hours proteinuria (1,104 mg), normal renal function, normal hepatic function, and ascitic liquid without alterations. The following tests: ANA (anti-nucleus antibody), anti-HCV (hepatitis C virus), anti-HIV and HBsAG (Hepatitis B surface antigen) presented negative results. Radiological examinations confirmed the presence of bilateral cubital pterygium, iliac horns and absent patella (Figure 2).

Figure 2 - Lateral x-ray of leg bones showing that the patella was absent.

Computed tomography of abdomen showed splenomegaly and absence of the intrahepatic portion of inferior vena cava (Figure 3), confirmed by venography (Figure 4). The congenital alterations described were in accordance with the diagnosis of NPS, developing with nephropathy and agenesis of inferior vena cava. The patient refused to undergo renal biopsy for confirmation of renal involvement and is currently fine, following regular visits.

Figure 3 - Abdominal computed tomography showing the absence of the inferior vena cava.

Figure 4 - X-ray of intraabdominal veins using contrast dye showing the absence of the inferior vena cava.

DISCUSSION

Patients who have nail-patella syndrome may show a variety of clinical symptoms. The syndrome may be complete, with the presence of the characteristic tetrad of pathologic symptoms, or incomplete, showing only some isolated alterations. The most commonly found features are nail dystrophy, with triangular lunulae in one or more fingers or the complete absence of fingernails of thumbs. The other fingernails may be underdeveloped, thin and short and the toenails are least likely to be affected.

Dysplasia observed in patellas also shows to be variable. They may be missing or poorly developed, and if present, patellas are likely to be laterally dislocated, causing difficulty in walking, once patellar tendons are hypoplastic. Quadriceps contraction and atrophy of vastus medialis are common findings; signs of knee osteoarthritis are frequent and early noticed. Other skeletal abnormalities may be malformation of the sternum, scapula, and clavicles and congenital talipes equinovarus and talipes valgus may be also present. The iliac horns, which are detected only by x-ray, appear as iliac spurs after antero-superior iliac crests and they are pathognomonic of NPS, being present in 80% of cases. Affected individuals may also demonstrate underdevelopment (hypoplasia) of the rounded projection of the thighbone (femur) that anchors to the head of the shinbone (lateral femoral condyle). The portions of bone that meet at the elbow may be hypoplastic, and there may be occasional subluxation of the head of radius. Due to such abnormalities, patients may be unable to completely rotate the arms inwards and outwards, with atrophy of the surrounding muscles.

Nephropathy is a serious disorder and it is present in about 30 to 55% of patients.^13-15 It may present simple proteinuria to severe acute renal insufficiency. Microscopic hematuria, leukocytes in the urine, abnormal urinary concentration, reduction of creatinine clearance and hypertension may be associated with proteinuria. Optical microscopy examination revealed different patterns, the most common is thickening of the glomerular basal lamina, with or without expansion of the mesangial matrix or cellularity. Endothelial proliferation and epithelial cells may occur. Deposits of fibrillar material within the basal lamina and/or mesangium could be observed by electron microscopy. Usually, patients with this type of renal involvement may present associated skeletal abnormalities; a minority does not present abnormalities, probably due to the incomplete gene penetrance in the syndrome.

Some associations with self-immune diseases like Goodpasture syndrome, vasculitis (polyarteritis nodosa) and other primary nephropathies (membranous glomerulonephrite) have been reported.

Our patient presented four characteristic diagnostic of NPS: absent patellas, nails dysplasia, bone spurs in the illiac bones and malformations in the head of radius, configuring the classical form of NPS. The first two findings are essential in the diagnosis,¹⁶ whilst the last ones, although pathognomic, are present only in 70 to 80% of cases.^16-18 Concomitant renal involvement could not be assessed through biopsy and related to the pathology, although the overall investigation to diagnose a secondary glomerular disease was negative. There was not any sign of self-immune disease, as well as any positive serology for viruses. It is possible that the proteinuria is related to the NPS. Another extremely significant finding was the presence of large-volume ascites with collateral circulation and signs of portal hypertension, with varicose veins in the esophagus evidenced by digestive endoscopy.

Hepatic problems are not described for NPS, and the patient did not have any hepatic disorder evidenced through laboratory tests or alterations in the image procedures suggesting hepatic diseases. The absence of the inferior vena cava was detected through computed tomography and venography, in its full extension, including intrahepatic. This could justify the portal hypertension of this patient, and there are not previous reports in the literature of the association of NPS with agenesis of inferior vena cava.

CONCLUSION

The authors suggest that patients with NPS with signs of portal hypertension should undergo image examinations (computed tomography and venography) in order to detect agenesis of inferior vena cava associated with this syndrome.

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