Pure spasticity

12%

—

Epileptic seizures

82%

—

Dystonic attacks

33%

—

Gastrointestinal

Feeding difficulties

100%

GERD

73%

—

Sleep disorder

96%

—

Apnea

67%

—

Recurrent infections

52%

Based on 33 individuals homozygous for the common missense variant, p.Ala307Ser, from nonconsanguineous parents surviving until age 11 years Pregnancy is usually unremarkable. Newborns have no external dysmorphic features and no visceral abnormalities.

CHMP1A

PCH82

AR

MRI findings similar to those of PCH2

Microcephaly, delayed walking, variable foot deformities, chorea, dystonic posturing, impaired cognition EXOSC3 EXOSC8 SLC25A46

VRK1

PCH12,3 (See EXOSC3-PCH.)

AR

Pontine atrophy may not be present in some individuals.

Lower motor neuron deficits due to loss of anterior horn cells; manifestations of peripheral denervation incl weakness muscle hypotonia from birth; Mixed central (spastic, dystonic) peripheral pareses may be present in those w/prolonged survival; some children w/PCH1 die at an early age.4

40 genes (e.g., PMM25)

Congenital disorders of glycosylation (CDG); see also PMM2-CDG (CDG-Ia).

AR(XL)

Pontocerebellar hypoplasia w/superimposed atrophy, delayed myelination

Dysmorphic features, ataxia, organ failure in neonatal period

PCLO

PCH32

AR

—

—

RARS2

PCH62

AR

Very rare; CSF lactate concentration

—

RELN

Lissencephaly 2 (OMIM 257320)

AR

Classic lissencephaly w/coexistent cerebellar pontine hypoplasia

—

SEPSECS

PCH22

AR

Progressive cerebello-cerebral atrophy closely resembles mild PCH2.

Clinical findings closely resemble mild PCH2.

TOE1

PCH72

AR

PCH

Disorders of sex development VLDLR

VLDLR cerebellar hypoplasia

AR

Gross cerebellar hypoplasia, a flat ventral pons, simplified gyri

Ataxia ID AR = autosomal recessive; ID = intellectual disability; MOI = mode of inheritance; PCH = pontocerebellar hypoplasia; XL = X-linked 1. OMIM Phenotypic Series: Muscular dystrophy-dystroglycanopathy, type A 2. 3.

—

Palliative care

Refer to palliative care specialist.

When deemed appropriate by family care providers Genetic

counseling

By genetics professionals1

To inform affected individuals their families re nature, MOI, implications of TSEN54-PCH2 to facilitate medical personal decision making Family support/ resources

Treatment of Manifestations in Individuals with TSEN54 Pontocerebellar Hypoplasia Type 2 Manifestation/Concern

Treatment

Considerations/Other

Seizures

Per standard practice

By neurologist experienced in epilepsy management

Irritability

None

Often related to chorea (involuntary movements)

Musculoskeletal

Multidisciplinary neuromuscular clinic physical medicine, OT/PT

Maximize gross motor fine motor skills through PT/OT use of adaptive devices.; Alternative casting/splinting stretching Orthopedics

Dysphagia

Gastroenterology / nutrition / feeding team

Modify food consistency to aspiration risk /or consider NG feeding gastrostomy.

Speech

Speech/language eval

Consider involving speech therapist OT to improve communication skills.

Respiratory

Manage pulmonary complications; treatment of respiratory infections

Per treating pulmonologist

Neurodevelopmental

Early intervention / individual education program based on needs

See . NG = nasogastric, OT = occupational therapy, PT = physical therapy The following information represents typical management recommendations for individuals with developmental delay / intellectual disability in the United States; standard recommendations may vary from country to country.