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4H syndrome, dento-leukoencephalopathy or a new syndrome?
  1. G Sinha1,
  2. I Anand1,*,
  3. S Agrawal2
  1. 1Paediatrics, Walsall NHS Trust, Walsall, UK
  2. 2Paediatric Neurology, Birmingham Children's Hospital, Birmingham, UK


Background Leukoencephalopathies in children can pose a diagnostic problem. New conditions with associated non neurological features have been described such as 4H syndrome (hypomyelination, hypodontia and hypogonadotropic hypogonadism) and Dento-leukoencephalopathy (hypodontia, white matter abnormalities and cortical atrophy). Both conditions appear to be related, but further research is needed to confirm or to identify new syndrome.

Aims The aim of this paper is to highlight the importance of recognising the additional non neurological features as an aid to diagnosis of leukoencephalopathies.

Methods We present a 17 year old Somalian girl born to consanguineous parents who moved to UK in 2005. She presented aged 12 to the Orthodontist with hypodontia and microdontia. She also had sparse hair, small oral opening, frontal bossing, small palpebral fissures. Last year, at the age of 15, she was referred with progressive loss of balance and joint pains. She displayed cerebellar signs as well as pyramidal tract signs which have progressed and she is now wheelchair bound. Her pubertal development was normal having attained menarche at 14 years. MRI scan of the brain showed high signal in corticospinal tracts, extending into centrum semiovale, posterior limb of internal capsule, posterior periventricular white matter and midbrain. Abnormal high signal was also seen along the trigeminal tracts. LHRH stimulation test showed insufficient rise in FSH and LH levels.

The combination of leukoencephalopathy with hypodentition indicated that this case was similar to those previously described in literature as dento-leukoencephalopathy and the related condition 4H syndrome.

However, our patient had additional features and normal pubertal development. We were intrigued with the LHRH stimulation test.

Conclusions The gene locus for 4H syndrome has been identified, but the specific gene is still not known. Genetic linkage tests are being undertaken to see whether the family maps in the region. There have been reports of autosomal recessive inheritance.

It is important in leukoencephalopathies to look for associated non neurological features like hypodentition, dysmorphism and hypogonadism. The condition may be under diagnosed and the identification of more patients will help clarify the genetic aetiology of this syndrome.

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