Table 3. [Autosomal Recessive Hereditary Spastic Paraplegias...]. - GeneReviews®

Gene(s)	Disorder	Clinical Features That Differ From SPG15
AP4B1 AP4E1 AP4M1 AP4S1	SPG47, SPG50, SPG51, & SPG52 (AP-4-assoc hereditary SPG)	Early-onset moderate-to-severe DD/ID, postnatal microcephaly, epilepsy, ventriculomegaly often in the shape of colpocephaly. Peripheral neuropathy is uncommon. ¹
AP5Z1	SPG48 ²	Onset of symptoms is often later, typically in adulthood ³
DDHD2	SPG54 ²	Optic nerve atrophy in a subset of affected persons
ERLIN2	SPG18 ²	Typically, onset of spasticity is in early childhood ⁴
FA2H	SPG35 (Fatty acid hydroxylase-associated neurodegeneration)	Optic nerve atrophy & oculomotor abnormalities are seen in a subset of affected persons. Atrophy of the pons is seen on brain MR imaging in the majority of affected persons. ⁵
GBA2	SPG46 ²	Ataxia is prominent. Hypogonadism in males.
SPG11	SPG11	No clinical features differentiate SPG11 & SPG15 w/certainty. Cerebellar signs, retinopathy, & hearing loss are less common in SPG11. ⁶
SPG21	SPG21 ² (Mast syndrome)	Onset of manifestations is often later, typically in early adulthood. Psychosis is seen in a subset of affected persons.
TECPR2	SPG49	Central apneas & autonomic dysfunction are prominent.

Gene(s)

Disorder

Clinical Features That Differ From SPG15

AP4B1
AP4E1
AP4M1
AP4S1

SPG47, SPG50, SPG51, & SPG52 (AP-4-assoc hereditary SPG)

Early-onset moderate-to-severe DD/ID, postnatal microcephaly, epilepsy, ventriculomegaly often in the shape of colpocephaly. Peripheral neuropathy is uncommon. ¹

AP5Z1

SPG48 ²

Onset of symptoms is often later, typically in adulthood ³

DDHD2

SPG54 ²

Optic nerve atrophy in a subset of affected persons

ERLIN2

SPG18 ²

Typically, onset of spasticity is in early childhood ⁴

FA2H

SPG35 (Fatty acid hydroxylase-associated neurodegeneration)

Optic nerve atrophy & oculomotor abnormalities are seen in a subset of affected persons. Atrophy of the pons is seen on brain MR imaging in the majority of affected persons. ⁵

GBA2

SPG46 ²

Ataxia is prominent. Hypogonadism in males.

SPG11

SPG11

No clinical features differentiate SPG11 & SPG15 w/certainty. Cerebellar signs, retinopathy, & hearing loss are less common in SPG11. ⁶

SPG21

SPG21 ² (Mast syndrome)

Onset of manifestations is often later, typically in early adulthood. Psychosis is seen in a subset of affected persons.

TECPR2

SPG49

Central apneas & autonomic dysfunction are prominent.

From: Spastic Paraplegia 15

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Adam MP, Feldman J, Mirzaa GM, et al., editors.

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