Thyroid hormone is absolutely necessary for early brain development. Incidence of thyroid disorders in infancy is 1:4,000. Thyroid hormones can be deficient through hormone synthesis and action or very rarely through defective transport. Some new and exciting transporters for tri-iodothyronine (T3) have recently come to light. MCT 8 gene encodes the protein that transports T3 into neurons. Its mutation result in inability of T3 to enter a developing brain neuron. This leads to peripheral elevation of T3 and TSH and low levels of T4. Clinically this causes a spectrum of neurological features known as Allan-Hendron-Dudley syndrome (AHDS). This X-linked mental retardation syndrome was described first in 1944.
We report a case of a male child born in 2002 with intrauterine growth retardation (IUGR). He was diagnosed with cerebral palsy with supportive MRI scan. His hypotonia, poor feeding and delayed milestones were attributed to this,although the phenotypic features of AHDS ie elongated facies, bifrontal narrowing, flat ears were also present. He had severe cognitive impairment and was not walking at 42 months. He continued to be hypotonic with athetoid movements. He was under a paediatric neurologist till his raised T3 and TSH levels were noted. He was then transferred to endocrinologist. The diagnosis of AHDS was on genetic studies. Thyroxin treatment has normalised his T4 and TSH.T3 remains elevated.
Thyroid hormone replacement does not correct any neurological deficits. Therefore ante-natal diagnosis is important. This case is unique as the mother was a mosaic carrier with no family history. Several families have been described in literature with affected male relatives. Largest series of 6 (Schwartz et al. 2005). It is important to recognise the defect early to plan counselling.Sex selection can also be offered for next pregnancy. Females have 1:2 chance of being a carrier while males have a 1:2 chance of inheriting the defective gene.
06 - 07 Nov 2006
Society for Endocrinology