Natural course of pontocerebellar hypoplasia type 2A

Abstract

IntroductionPontocerebellar hypoplasia Type 2 (PCH2) is a rare autosomal recessive condition, defined on MRI by a small cerebellum and ventral pons. Clinical features are severe developmental delay, microcephaly and dyskinesia.Ninety percent carry a p.A307S mutation in the TSEN54-gene. Our aim was to describe the natural course including neurological and developmental features and other aspects of care in a homogeneous group of PCH2 patients all carrying the p.A307S mutation.Patients and methodsPatients were recruited via the German patients' organizations. Inclusion criteria were imaging findings of PCH2 and a p.A307S mutation. Data were collected using medical reports and patient questionnaires discussed in a standardized telephone interview.ResultsThirty-three patients were included. When considering survival until age 11 years, 53% of children had died Weight, length and head circumference, mostly in the normal range at birth, became abnormal, especially head circumference (-5.58 SD at age 5 yrs). Neurologic symptoms: Choreathetosis was present in 88% (62% with pyramidal signs), 12% had pure spasticity. Epileptic seizures were manifest in 82%, status epilepticus in 39%. Non-epileptic dystonic attacks occurred in 33%. General symptoms: feeding difficulties were recorded in 100%, sleep disorder in 96%, apneas in 67% and recurrent infections in 52%; gastroesophageal reflux disease was diagnosed in 73%, 67% got percutaneous endoscopic gastrostomy and 36% a Nissen-fundoplication. Neurodevelopmental data: All children made progress, but on a low level: such as fixing and following with the eyes was seen in 76%, attempting to grasp objects (76%), moderate head control (73%), social smile (70%), rolling from prone to supine (58%), and sitting without support (9%). Ten percent lost achieved abilities on follow-up. The presence of prenatal symptoms did not correlate with outcome.ConclusionPhenotype of this genetically homogeneous group of PCH2 children was severe with reduced survival, but compatible with some developmental progress. Our data support the hypothesis of an early onset degeneration which thereafter stabilizes.

Brain Morphometry in Pontocerebellar Hypoplasia Type 2

“…Most but not all affected children at the age of 6 months and 10 years, illustrating the severe hypoplasia of pons and cerebellum already in infancy. Note that the scale of both images is identical, indicating hardly any brain volume increase after ten years of life (but thickened skull), with larger CSF spaces suggesting atrophy, with some frontal lobe dominance were normocephalic at birth (within 2 standard deviations), as also reported by others [3], but all showed progressive microcephaly falling below 5 standard deviations from the mean already in the second year of life, whereas both failure to thrive and short stature only fell below 2 standard deviations [6]. On conventional MRI, infratentorial structures are reported clearly abnormal shortly after birth and are the basis -along with clinical criteria -for defining PCH2: hypoplasia of the pons and dragonfly-like atrophy of cerebellar hemispheres with relative sparing of the flocculus and vermis [3].…”

“…All children with PCH2 were recruited as part of a natural history study [6] and with the support of the PCH2 parents' organization in Germany and Switzerland. Subjects were included if they met the clinical and MRIbased diagnosis accompanied by molecular testing of PCH 2 (homozygous mutation c.919G > T, p.A307S in TSEN54-gene).…”

Pontocerebellar hypoplasia: clinical case and literature review

“…Jø at lik ta me ty ri me, ku rio im tá su da rë 33 pa cien tai, ser gan tys PCH2A, 29 pa cien tams (88 %) ste bë ti cho re oa te toi di niai ju de siai, ta èiau vi du ti nið kai jie pa si reið kë 3,8 mën. amþiaus pa cien tams [6]. Pa na ðûs re zul ta tai ste bë ti ir ana li zuojant epi lep si jà -Na va mar ir kt.…”

“…Iciar Sánchez-Al bi sua ir kt. ty ri me trau ku liø pa si reið ki mo daþ nis bu vo 82 %, o vidu ti nis trau ku liø pra dþios am þius -2 me tai ir 5 më ne siai [6,9]. Mû sø ap ta ria mam pa cien tui kli nið kai átar ta epi lep sija, bu vo at lik tas EEG ty ri mas, ta èiau epi lep ti for mi niø paki ti mø ne re gist ruo ta.…”

“…am þiaus pa cien tams. Mû sø at ve ju PEG bu vo at lik ta apie 2 më ne siø am þiaus pa cien tui, nes mai ti nimo si su tri ki mai pa si reið kë nuo pat gi mi mo [6]. Taip pat mû sø pa cien tui bu vo ste bë ti daþ niau siai nak tá at si ran dantys de sa tu ra ci jos epi zo dai, ku rie, pa sky rus de guo ná per kau kae, pra nyk da vo.…”