Yellow nail syndrome presenting as non-immune hydrops: Second case report

INTRODUCTION

Samman and White [1964] delineated the yellow nail syndrome, reporting on 13 cases. The nails are typically slow growing, excessively curved and with a yellowish discoloration. They frequently show ridging due to interrupted growth with an overall slow rate of growth. Onycholysis can occur in one or more of the nails. The most consistent association is that of ankle edema due to lymphoedema, but other associations have been reported in adults, including more extensive lymphoedema, bronchiectasis and recurrent pleural effusions [Venencie and Dicken, 1984; De Coste et al., 1990]. Govaert et al. [1992] reported on a girl born at 33 weeks of gestation with non-immune hydrops and a recurrent left chylothorax, to a mother with the yellow nail syndrome. The non-immune hydrops in their case was diagnosed on a 29-week ultrasound examination.

Our case represents the second documented prenatal manifestation of the yellow nail syndrome, and confirms an unusual presentation of this rare disorder.

CLINICAL REPORT

A 5-year-old-boy was the only child of young, non-consanguineous parents. The pregnancy was uneventful until 23 weeks when antenatal ultrasonography detected polyhydramnios, fetal skin edema and bilateral pleural effusions (Fig. 1). There had been no maternal febrile illnesses, the mother was rhesus positive and her blood antibody screen was negative. In addition fetal cardiac anatomy appeared normal, with a normal cardiac rhythm. Cordocentesis was performed excluding chromosomal or hematologic abnormality, and results of viral studies, including the TORCH group and parvovirus, were negative. The pregnancy continued for a further 7 weeks before preterm rupture of membranes at 30 weeks of gestation and delivery of a hydropic male infant weighing 2,200 g with bilateral chylothorax. He had a stormy neonatal course, with ventilator assistance for 4 weeks, complicated by a spontaneous pneumothorax, the need for early inotrope support, prolonged conjugated hyperbilirubinemia due to neonatal hepatitis, 2 episodes of septicemia and a small right subependymal hemorrhage. Repeat viral serology was normal, blood group was O positive and a Direct Coombs test was negative. The chylothoraces did not reaccumulate after drainage, and, in particular, did not recur after introduction of feeds. He had persistent conjugated hyperbilirubinemia in association with mildly raised transaminases that persisted for 4 months. Liver biopsy was in keeping with neonatal hepatitis. At the age of 3 months he had bilateral inguinal hernia repairs, and at 2½ years was found to have moderately severe sensorineural deafness, for which he has been fitted with hearing aids.

At 5 years his developmental progress was normal, with no neurological sequelae. His nails were normal and there have been no further episodes of edema. He had developed a chronic non-productive cough, however, over the preceding 18 months. Chest radiography, including CT scan, was normal.

His mother, age 33 years, had developed yellow, hypertrophic poorly growing nails (Fig. 2) with increased lateral curvature (Fig. 3) over the past 6 years. Over this period she had also developed recurrent episodes of a productive cough. Lung function tests showed mild reversible airflow obstruction, immunoglobulins were normal and CT scan of her chest demonstrated bronchiectasis in the lingular segment of the left upper lobe along with the medial and lateral segments of the right middle lobe. She smoked one cigarette per day between the ages of 15 and 23. The pregnancy was unaffected by hypertension, but she had transient edema of the arms and legs with no subsequent episodes.

DISCUSSION

Yellow nail syndrome (YNS) is a rare disorder characterized by slowly growing yellow dystrophic nails and peripheral lymphoedema. Over 100 cases have been published, with a female predominance of 1.6:1 [Nordkild et al., 1986]. Many of the reported cases have been sporadic, in addition to reports of autosomal dominant inheritance with variable expression [Wells, 1966; Emerson, 1966, Kleinman, 1973]. The condition may be heterogeneous, given the report of two affected sibs with intellectual handicap and consanguineous parents (double first cousins), suggesting autosomal recessive inheritance in this particular family [Kamatani et al., 1978].

Associated abnormalities in the yellow nail syndrome (YNS) include bronchiectasis, pleural effusions, chronic sinusitis, chylous ascites and immune deficiency [Siegelman et al., 1969; Venencie and Dicken, 1984; Duhra et al., 1985; De Coste et al., 1990]. In a review by Nordkild et al. [1986] 90% of affected patients with the YNS had the classic yellow nails, that was the initial presenting sign in 37%. Lymphoedema was present in 80%, and was the initial presenting sign in 34%, with 63% developing pulmonary manifestations. The latter was the initial presenting finding in 29%. Other less commonly reported associations include renal (chyluria and Nephrotic syndrome) [Cockram and Richards, 1979; Toal et al., 1988] and rheumatoid arthritis [Mattingly and Bossingham, 1979]. Bull et al. [1996] suggested that the abnormality of the lymphatics was a functional rather than a structural problem, and this would be supported by the recovery of both the child in this report, and the child described in the report by Govaert et al. [1992] from their hydrops.

YNS usually manifests in puberty, although there have been a few reports of the syndrome manifesting in childhood [Zerfas and Wallace, 1966; Kleinman, 1973; Magid et al., 1987]. Govaert et al.[1992] reported on a 33-week newborn infant who presented with hydrops and a recurrent left chylothorax. His mother had the YNS. The hydrops had been diagnosed on a 29-week antenatal ultrasound study, and extensive laboratory work-up had failed to delineate an alternative cause for the hydrops in this child. At one year the only manifestation was mild lymphoedema of ankles and cutis marmorata. The only other potential report of a similar early presentation was the brief reference to a 4-month-old sib of an affected 11-year-old girl who died with ‘total body edema’ [Kleinman, 1973].

Paradisis and Van Asperen [1997] reported the ‘yellow nail syndrome’ in an infant who presented with congenital lymphoedema, and at 6 months of age represented with bilateral pleural effusions and a pericardial effusion, with ongoing problems with middle ear effusions and immunodeficiency. His nails were normal and there was no reported family history of YNS. The classic triad includes dystrophic yellow nails, lymphoedema and pleural effusions, but not all patients have all of these signs, and additionally the nail changes often do not present until adulthood, so a definitive diagnosis in their case is not yet possible. A report by Jones [1960] in which 5 of 7 infants with peripheral edema also had dystrophic nails may represent early infantile manifestations of the condition.

Our case is the second known to us with yellow nail syndrome and non-immune hydrops. The deafness in the child in this report may be related to the condition, but other possible explanations are the stormy neonatal course, including the requirement for aminoglycoside antibiotics. Conductive deafness with YNS has been reported [Paradisis and Van Asperen, 1997], but there have been no reports of sensorineural deafness, although the association of sensorineural deafness with congenital lymphoedema and leukemia has been described in one report [Emberger et al., 1979].

The recurrent cough developed by the child in this report raises the possibility of the early onset of bronchiectasis. Whether the early prenatal onset is associated with an earlier onset of other manifestations is uncertain and may become apparent at long term follow-up.

Familial lymphoedema presenting in one family member as mild lymphoedema and in a sibling as severe hydrops fetalis has been described in other conditions [Irons et al., 1996]. The severity of manifestations in the infant reported by Govaert et al. [1992] and the child in this report, together with previous reports of variable expression might suggest the phenomenon of anticipation. There are insufficient well-documented cases in the literature of an affected parent and child, however, to either support or refute this hypothesis. Ascertainment bias with a more severely affected child alerting the clinician to mild manifestations in a parent is likely to further complicate the situation. Therefore careful follow-up and documentation of families with YNS would be important in attempting to answer this question.