Genetic Syndromes Presenting in Childhood Affecting Hypothalamic Function

Abstract

This chapter will focus on two genetic syndromes affecting hypothalamic function that typically present in childhood, Prader-Willi syndrome, and congenital optic nerve hypoplasia.

Prader-Willi syndrome (PWS) is a complex and challenging rare disorder resulting from the absence of gene expression on the paternal chromosome 15q11.2–q13. First described in 1956 as a medical syndrome, the chromosome 15 deletion was discovered in 1981. PWS is a spectrum disorder with a complex phenotype. The universal hallmark is hypotonia with decreased foetal activity noted during pregnancy. Most neonates are born with a lack of suck and respiratory irregularities. They are sleepy and seldom cry. Hypotonia and failure to thrive in infancy evolve into rapid weight gain in early childhood often with insatiable appetite and food seeking; this will lead to profound life-threatening obesity if not well managed at home and in school. Hypothalamic impairments complicate day-to-day life—high pain tolerance, temperature dysregulation, sleepiness, and constant drive to eat. Pituitary deficiencies of growth hormone and GnRH require skilled endocrine care throughout the lifespan. Children with PWS are at risk for respiratory crises from central apnoea and hypotonia with poor ventilatory effort in infancy and aspiration from impaired swallowing motility. Intellectual abilities span a wide spectrum although many children are successful in mainstream classrooms. Unique behavioural patterns including perseveration, skin picking, anxiety, and difficulty with task switching are common. With early diagnosis and intervention, developmental progress, health, and family stress can be significantly improved. Families need diagnosis-specific interventions with specialized medical care throughout the lifespan. Researchers are expanding understanding of PWS. Children born in the past two decades enjoy improved quality of life over previous generations. Treatment remains symptom driven, with no cure for the gene deletion.

Congenital optic nerve hypoplasia is correlated with pituitary dysfunction and developmental brain abnormalities. Nystagmus in infancy should be promptly assessed in the endocrine setting as pituitary deficiencies can include life-threatening hypoglycaemia and shock. Newborn screening programmes designed for congenital hypothyroidism seldom detect thyroid stimulating hormone (TSH) deficiency leaving these babies at high risk of hypothyroidism at the most critical time. Visual impairment ranges from unilateral visual field defects to bilateral complete blindness; pituitary deficiencies can be complete deficiencies of all hormones with prenatal onset, or development of insufficiencies over time. Brain abnormalities noted on magnetic resonance imaging (MRI) have relevance in predicting developmental and intellectual challenges, which occur in a wide spectrum. Endocrine nurses have a critical role in supporting and educating these families, and in helping them understand the unique impact of visual impairment on the child’s development and behaviour.