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HEREDITARY MONOGENIC DISEASES

           

Pontocerebellar hypoplasia

Pontocerebellar hypoplasia (PCH) is a group of rare, inherited neurodegenerative disorders with prenatal onset.

So far seven different subtypes have been reported (PCH1-7). The incidence of each subtype is unknown. All subtypes share common features, including hypoplasia/atrophy of the cerebellum and pons, progressive microcephaly, and floating brain involvement. They have seizures plus motor involvement.

The types of pontocerebellar hypoplasia related to the TSEN54 gene are 2, 4 and 5.

Pontocerebellar hypoplasia type 2 (PCH2) is the most common subtype of pontocerebellar hypoplasia characterized by neonatal onset and a lack of voluntary motor development and later progressive microencephaly, generalized clonus, development of chorea and spasticity. The majority of patients will not reach puberty. PCH2 is reported in at least 81 families to date. Diagnosis is made is based on a combination of neuroradiologic and clinical findings : MRI demonstrates variable neocortical atrophy, progressive in time, flattening of the caudate nuclear heads, and pontocerebellar hypoplasia with a typical dragonfly-like cerebellar pattern on coronal sections caused by the flat hemispheres heavily reduced in size together with a comparatively spared vermis.

Pontocerebellar hypoplasia type 4 (PCH4) is a very rare form of PCH characterized by prenatal onset of polyhydramnios and contractures followed by hypertonia, severe clonus, primary hypoventilation leading to an early postnatal death. Neonates present with microcephaly, central apnea requiring respiratory support, dysmorphism (sloping forehead, midface hypoplasia, micrognathia), contractures (50%) ”arthrogryposis”, severe clonus,and hypertonia. PCH4 affected babies usually do not live beyond the neonatal period. MRI (usually performed at autopsy) demonstrates microcephaly due to delayed neocortical maturation with underdeveloped cerebral hemispheres, increased volume of extracerebral cerebrospinal fluid, wide midline cava, pontocerebellar hypoplasia with large denuded areas without folia of the cerebellar hemispheric cortex and a severely affected vermis.

Pontocerebellar hypoplasia type 5 (PCH5) is a very rare severe form of PCH with prenatal onset and characterized by fetal onset of clonus or seizures-like activity persisting in infancy and microencephaly leading to early postnatal death. There is significant overlap both in phenotype and in genotype between pontocerebellar hypoplasia types 4 and 5.

The treatment for all types of pontocerebellar hypoplasia is only symptomatic and the prognosis is bad, since most patients die during infancy or childhood.

GENE OR REGION STUDIED


  • TSEN54