Term baby with central hypotonia: Neonatal presentation of a rare disease - A case report

INTRODUCTION

Central hypotonia in the neonatal period presents a significant diagnostic and management challenge. Among the various genetic etiologies, Prader-Willi Syndrome (PWS) is an important and relatively common cause. It is characterised by hallmark features including pronounced hypotonia, poor feeding, hypogonadism, and distinctive craniofacial features. This case report highlights the early clinical presentation of PWS in the neonatal period, the diagnostic dilemmas encountered, and the approach to management in a resource-constrained NICU setting.

CASE REPORT

A male newborn was delivered through cesarean section at 37 weeks of gestation from a third-degree consanguineous marriage to a 25-year-old multigravida mother. He presented with generalized hypotonia at birth. The mother’s prenatal course was uneventful, with no significant medical issues or obstetric complications. Her antenatal scans showed no abnormalities, such as polyhydramnios, and there was no history of decreased fetal movements.

The neonate did not cry immediately after birth and had appearance, pulse, grimace, activity, and respiration (APGAR) scores of 4 and 6 at 1 and 5 min of life, respectively. He required resuscitation with bag and mask ventilation for 30 s and, then, had good spontaneous respiratory efforts. However, at 5 min of life, he had mild respiratory distress requiring low-flow oxygen therapy (1 L/min with fraction of inspired oxygen (FiO₂₎ of 25%). There was no history of seizures. Anthropometry as per the World Health Organization growth chart is as follows: Birth weight: 2400 g (3^rd–10^th centile), head circumference 34.5 cm (10^th– 50^th centile), and length 50 cm (10^th–50^th centile).

On examination, he had an abnormal face with a prominent forehead, depressed nasal bridge with a pointed tip of nose, prominent gum, downturned mouth, small mandible [Figure 1], and small scrotum with decreased rugae with bilateral undescended testis [Figure 2]. He had poor responsiveness to external stimuli, a weak cry, and a poor repertoire of spontaneous movements. Rooting and sucking reflexes were reduced; however, there was no drooling of saliva or pooling of secretions. The posture of the neonate appeared “frog-like” with abduction at the bilateral hip and arm, with complete head lag suggestive of global hypotonia [Figure 3]. Power in the muscles of both upper and lower limbs was normal. Deep tendon reflexes were also normal. There was no hepatosplenomegaly, and the rest of the systemic examination was normal.

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Figure 1:

Prominent forehead, downturned mouth, and protuberant abdomen with frog-like posture.

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Figure 2:

Bilateral undescended testis.

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Figure 3:

Head lag suggesting hypotonia.

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DISCUSSION

PWS is a disorder of genetic imprinting with maternal disomy wherein both the maternal genes are on the proximal part of the long arm of chromosome 15, with del15 (q11q13) seen in up to 70% cases. The reported incidence is about one in 10,000–15,000 live birth.^[1]

The prenatal presentation of PWS includes decreased fetal movements, fetal malpresentation, severe intra-uterine growth restriction, and polyhydramnios.^[2] In the index, neonate however has no such features antenatally.

Although there are no specific diagnostic criteria for children 3 years or younger, the diagnosis of PWS can be made based on the diagnostic criteria, as mentioned in Table 1.^[3]

Major criteria are weighted at one point each. Minor criteria are weighed at one-half point. Children 3 years of age or younger: Five points are required for diagnosis, four of which should come from the major group. The index neonate had five major and one minor criteria with a score of 5.5, leading to the diagnosis of PWS.

The clinical phenotype of PWS has two distinct phases: The “neonatal hypotonia” phase and the later “hyperphagic” phase. Problems related to feeding form the core management issue in the neonatal period, which feeding difficulty seen in up to 90% of neonates.^[3] As in our index neonate, the factors predisposing for this include (A) reduced oromotor tone (B) poor and immature suck reflex (C) swallowing dysfunction. The incoordination of the suck-swallow and breathing is a major hindrance to the establishment of breastfeeding. This feeding difficulty often leads to severe failure to thrive by 6 months of age in 15% of infants.^[4] This is complicated further compounded by the presence of endocrine dysfunction due to growth hormone deficiency and hypogonadism seen in later infancy. The average duration of requirement of tube feeding in neonates with PWS is 15-35 days. However in this index neonate we were able to establish breastfeeding by DOL-18. Following this phase, certain infants have a phase of excessive weight gain leading to obesity and this is due to orexin stimulation due to neurological dysfunction. Hypotonia is another universal finding in neonates with PWS. This is considered secondary to inactivating mutations in the MAGEL2 gene.^[5] This is non-progressive and tends to improve by 8–11 months of age.^[6]

PWS is the result of a de novo genetic alteration with most families having a recurrence risk of <1%. With early recognition and structured follow-up care, the children have a better quality of life and survival up to 45 years.^[7]

CONCLUSION

Clinicians should suspect Prader–Willi syndrome (PWS) in neonates presenting with global hypotonia, feeding difficulties, and characteristic facial features, even in the absence of antenatal markers. Prompt initiation of oromotor stimulation, early intervention and structured feeding therapy in the NICU setting is essential to facilitate early establishment of breastfeeding, Regular follow-up is critical to monitor for and manage potential complications such as growth failure, obesity, and endocrine dysfunction. All these significantly improve long-term quality of life and developmental outcomes in affected infants.