Neonatal Subdural and Extradural Haemorrhage in Prader-Willi Syndrome

Sir,

Prader, Labhart, and Willi in 1956 described a condition with the characteristic features of obesity, short stature, and developmental delay [[4]]. Prader-Willi syndrome (PWS) is a neuroendocrine disorder. 70 % of patients with PWS have a characteristic deletion of the proximal part of the long arm of chromosome 15 (15 del[q11q13]) and 30 % have maternal uniparental disomy or rarely abnormal methylation at chromosome 15q11 - 13 [[5]]. Typically, children are born at term but are small for gestational age, 30 % are breech. They present with profound muscular hypotonia, swallowing difficulties, and hypogonadism. Obesity, moderate learning disability, behaviour problems, and hyperphagia may present in childhood or adolescence [[2]].

We observed an infant with Prader-Willi syndrome and bilateral subdural and extradural haemorrhage and effusions without any signs of birth trauma or identifiable coagulopathy. Subdural and extradural haemorrhage have not been previously reported in association with PWS.

The child was the second son of healthy, unrelated parents. At 34 weeks gestation an ultrasound scan showed reduced fetal growth and a transverse lie. For this reason delivery was by Caesarean section at 39 weeks gestation. A male infant was delivered in an extended breech position. His birth weight was 2.53 kg (2nd centile) and his head circumference was 34.5 cm (25th centile). Clinical examination revealed generalised hypotonia with no movements of the lower limbs and reduced spontaneous movements of the upper limbs. Deep tendon reflexes were absent. Spontaneous eye opening was noted. He had a weak, high-pitched cry, swallowing difficulties and a poor suck which necessitated nasogastric tube-feeding. In addition he had dysmorphic features: Bilateral single palmar creases, divarication of recti, and bilaterally undescended testes. He had bilaterally dislocated hips and tended to hold both thumbs adducted although they did straighten on passive movements.

Molecular genetic investigation for PWS by Southern blot detected a 4.2 kb band only at KB17 and confirmed the diagnosis of PWS.

Due to the clinical impression of central hypotonia, investigations included magnetic resonance imaging at the age of 10 days which revealed moderately sized bilateral subdural collections which were blood stained. A small focal area of haemorrhage was seen along the posterior aspect of the falx. The subarachnoid space was capacious and additionally there were shallow extradural collections over the convexity (Fig. [1]). To determine the cause of these effusions, several investigations were undertaken to identify a bleeding diathesis: Full blood count, clotting (prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, platelet count), platelet function tests and factor XIII were all within the normal range. Serum lactate, plasma amino acids, urine organic acids, and peroxisomal function tests were also normal.

Fig. 1 Magnetic resonance brain scan (T₁-weighted, sagittal and coronal views) at 10 days of age shows bilateral blood stained subdural collections, a focal area of haemorrhage along the posterior falx, and extradural collections over the convexity.

Subdural haemorrhage in term neonates is an uncommon form of intracranial haemorrhage (less than 0.5 per 1000 deliveries) [[6]] as is the incidence of extradural haemorrhage in association with subdural haematomas (5.9 %) [[3]]. While trauma [[7]], bleeding diathesis [[1]] and skeletal abnormalities predispose to these forms of intracranial haemorrhage, other causes and risk factors are poorly understood [[6]]. This may place the paediatrician in a difficult position if trauma is suspected, as accurate diagnosis of the cause of haemorrhage is important in the legal process.

In our case no evidence of trauma, bleeding diathesis, or skeletal abnormality was found. No skull fracture or cephalhaematoma were clinically identified. Breech delivery has been shown to be a predisposing factor for subdural haemorrhage [[6]]. Caesarean section itself is not a risk factor but the indications for the section (e.g., foetal distress) may be. In our patient the indication for the Caesarean section was the transverse lie, which has not been previously described as a risk factor for intracranial haemorrhage. Some other relative risk factors have been cited, such as increasing maternal age (42 years in this case), low parity, large neonatal size, gestational age with greater risk at term, male sex [[6]]. These risk factors have been reported in births with “normal” labour and delivery but their role in causing intracranial haemorrhage remains unproven. Besides bleeding abnormalities such as factor X and factor XIII deficiency [[1]], other rare reported associations are glutaric aciduria type 1 and hereditary haemorrhagic teleangiectasia.

There is some evidence for genetically based abnormal homoeostasis in patients with PWS which possibly predisposes them to acute gastric dilatation [[8]]. Gastrectomy specimens of six patients with PWS and dramatic acute gastric dilatation showed diffuse mucosal infarction, vascular dilatation, and small fibrin thrombi within the infarcted areas.

This raises the possibility of a genetically based abnormality of homeostasis in PWS which could lead to extracerebral haemorrhage. It may be that cryptogenic subdural or extradural collections have occurred in other newborns with PWS. Evaluation of brain imaging could help to detect similar or more subtle intracranial lesions in newborns with PWS.

In conclusion, the extracerebral haemorrhage could have been the result of perinatal risk factors in this infant or may have been caused by an unidentified genetically based abnormality of homeostasis in PWS.

References

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