Noonan syndrome (NS)[OMIM 163950] was first described by Noonan and Ehmke [1963]. It has an estimated frequency of between 1: 1,000 and 1: 2,500 live births [Noonan, 1994, 1999]. The diagnosis of NS is made on the basis of clinical criteria including characteristic facial traits such as long forehead, hypertelorism, downslanting palpebral fissures, ptosis, lowset, posteriorly angulated ears, short neck with excess nuchal skin, low posterior hair line, short stature, delayed puberty, congenital heart defects, and other congenital anomalies. At least 50% of cases of NS have been found to have a mutation in the PTPN11 gene [Tartaglia et al., 2001; Zenker et al., 2004]. Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by widespread inflammation of blood vessels and connective tissues, in association with the presence of antinuclear antibodies (ANA), particularly antibodies to double-stranded DNA. The incidence of SLE in children has been reported at approximately 0.36 per 1, 00,000 children per year [Malleson et al., 1996]. It is very rare in children under the age of 5 years, with the annual incidence increasing throughout childhood, reaching a peak of about 7.6 per 1, 00,000 in adulthood [Petri, 2002]. Three cases of NS with SLE are reported [Martin et al., 2001; Amoroso et al., 2003; Alanay et al., 2004]. Another report from Yamashita et al.[2004] details a patient with NS, Moyamoya vascular changes, and antiphospholipid syndrome with positive testing for anticardiolipin antibody, ANA, and lupus anticoagulant. In addition there are numerous reports of NS patients with various types of autoimmune disorders [Chaves-Carballo and Hayles, 1966; Vesterhus and Aarskog, 1973; Berberich and Hall, 1976; Sharland et al., 1992]. We report on a 5-year-old girl with NS and SLE, the youngest child described to date with both disorders serving to identify further an increasingly recognizable association between NS, SLE, and potentially other auto-immune mediated diseases.

Our patient was born normally at 38 weeks of gestation. Birth weight was 3.6 kg (50%). The pregnancy was uncomplicated. Review of the family history showed that her parents were nonconsanguineous. The rest of the family history was unremarkable and careful examination of the parents did not show any manifestation of NS. The diagnosis of NS in our patient was made at age 3½ years based on characteristic facial appearance, small stature, concentric left ventricular hypertrophy, and mild developmental delay (Fig. 1). Karyotype was normal (46, XX) at 450–550 band resolution. At age 5 she presented with lethargy, decreased appetite, hematuria, proteinurea, arthritis of the right knee, peripheral edema, ascites, mild respiratory distress, a small left pleural effusion, hypertension, and pancytopenia. Initial concerns about malignancy prompted a bone marrow aspiration that showed signs suggestive of peripheral consumption of platelets and neutropenia. A renal biopsy showed diffuse proliferative lupus glomerulonephritis (WHO class IV). Magnetic resonance angiography showed equivocal signs of cerebral vasculitis; however, conventional cerebral angiography was normal. She fulfilled 1997 ARC classification criteria for SLE with glomerulonephritis, Coombs positive hemolytic anemia (Hb 69 gm/L), thrombocytopenia (100Â 109/L), high titre ANA (> 1: 1,280), and raised antibodies to DNA (15 kU/L) and anticardiolipin antibodies (IgG 36.2 MOM). Her latest EKG showed sinus rhythm with axis slightly rightward with no definite ventricular hypertrophy. Her echocardiogram shows mils septal thickening. She is presently stable on her current treatment regimen.