Table 1.
Overview of the clinical presentation of the families in our cohort with the OMIM corresponding identity deduced from the genetic results.
| Family code | Clinical features observed in patients | OMIM phenotype (MIM ID) | Gene |
|---|---|---|---|
| F8 | Cerebellar ataxia, cataract, and hypotonia | Marinesco-Sjogren syndrome (# 248800) | SIL1 |
| F27 | Stunted growth, dysmorphic features, microcephaly, cerebellar ataxia, and retinitis pigmentosum | Cockayne syndrome A (# 216400) | ERRC8 |
| F31 | Cerebellar ataxia and developmental delay | Cerebellar ataxia, mental retardation, and disequilibrium syndrome 1 (# 224050) | VLDLR |
| F38 | Cerebellar ataxia | Friedreich ataxia (# 229300) | FXN |
| F41 | Cafe-au-lait spots, cerebellar ataxia, and skeletal deformities | Neurofibromatosis, type 1 (# 162200) | NF1 |
| F49 | Cerebellar ataxia, spasticity, and dysarthria | Machado-Joseph disease (# 109150) | ATXN3 |
| F53 | Spastic limbs, wasting, and low-set ears | Spastic paraplegia 11, autosomal recessive (# 604360) | SPG11 |
| F54 | Developmental delay and spastic limbs | Spastic paraplegia 48, autosomal recessive (# 613647) | AP5Z1 |
| F57 | Spastic limbs, skeletal deformities, cerebellar ataxia, wasting, and weakness | Spastic ataxia, Charlevoix-Saguenay type (# 270550) | SACS |
| F59 | Intellectual disability, spastic limbs, and skeletal deformities | Spastic paraplegia 45, autosomal recessive (# 613162) | NT5C2 |
| F61 | Regressed developmental milestones, spastic limbs, cerebellar ataxia, and ophthalmoplegia | Spastic paraplegia 35, autosomal recessive (# 612319) | FA2H |
| F62 | Stunted growth, intellectual disability, spastic limbs, dysarthria, wasting, and cerebellar ataxia | Cockayne syndrome B (# 133540) | ERCC6 |
| F63 | Intellectual disability, aggression, dysmorphic features, squint, skeletal deformities, and spastic limbs (ref. 19) | Mental retardation, autosomal recessive 36 (# 615286) | ADAT3 |
| F66 | Developmental delay, spastic limbs, and weakness | Novel phenotype in a known gene not associated previously with SCD | DMXL2 (VUS) |
| F67 | Cerebellar ataxia, epilepsy, and learning disability | Ceroid lipofuscinosis, neuronal, 7 (# 610951) | MFSD8 (VUS) |
| F68 | Abnormal gait, spasticity, and cerebellar ataxia | Spastic paraplegia 35, autosomal recessive (# 612319) | FA2H |
| F70 | Weakness, wasting, dysphagia, developmental delay/regression, and unsteady gait | Leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism (# 607694) | POLR3A |
| F76 | Developmental delay, spasticity, wasting, and skeletal deformities | Spastic paraplegia 54, autosomal recessive (# 615033) | DDHD2 |
| F78 | Spasticity, cerebellar ataxia, weakness, intellectual disability, and ears of the lynx sign on MRI | Spastic paraplegia 15, autosomal recessive (# 270700) | ZFYVE26 |
| F79 | Developmental delay, dysmorphic features, abnormal gait, autistic features, and behavioral disturbances (ref. 19) | Mental retardation, autosomal recessive 38 (# 615516); spinocerebellar ataxia, X-linked 1 (# 302500) | HERC2/ ATP2B3 (VUS) |
| F80 | Developmental delay, spastic limbs, and skeletal deformities | Spastic paraplegia 45, autosomal recessive (# 613162) | NT5C2 |
| F81 | Developmental delay, spastic limbs, and epilepsy (ref. 19) | Novel phenotype in a known gene not associated previously with SCD. | CCDC82 |
| F82 | Global developmental delay, microcephaly, dysmorphic features, epilepsy, and spastic lower limbs | Mental retardation, X-linked, syndromic, turner type (# 309590) | HUWE1 |
| F83 | Early-onset pure hereditary spastic paraplegia (ref. 19) | Spinocerebellar ataxia 40 (# 616053) | CCDC88C |
| F84 | Developmental delay/regression, microcephaly, squint, and generalized spasticity | Mucolipidosis IV (# 252650) | MCOLN1 |
| F85 | Deafness and mutism, mild cerebellar ataxia, spasticity | Deafness, autosomal recessive 84a (# 613391) | PTPRQ (VUS) |
| FM3 | Global developmental delay, spastic limbs, and skeletal deformities (ref. 27) | Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (# 617481) | PRUNE1 |
| FM6 | Spasticity and ocular cerebellar signs (ref. 39) | Leukoencephalopathy with brainstem and spinal cord involvement and lactate elevation (# 611105) | DARS2 |
| The undiagnosed families | |||
| F5 | Spasticity and cerebellar ataxia | Not applicable | |
| F46 | Skeletal deformities and cerebellar ataxia | Not applicable | |
| F74 | Weakness, myopathic faces, contractures, and hypophonia | Not applicable | |
| Families with mutations in candidate novel genes | |||
| F7 | Pure hereditary spastic paraplegia | Unpublished | |
| FM2 | Cerebellar ataxia, spasticity, epilepsy, dysphagia, extrapyramidal features, and brain MRI white matter abnormalities. | Unpublished | |
| F65 | Late-onset ataxia and spasticity | Unpublished | |
| F69 | Febrile convulsions, global developmental delay, spastic limbs, and skeletal deformities (ref. 30) | Spastic Paraplegia 86, autosomal recessive (# 619735) | ABHD16A |
| F73 | Slurred speech, gait abnormalities, and epilepsy | Unpublished | |
| F75 | Weakness and spasticity | Unpublished | |
| F77 | Global developmental delay, spasticity, and convulsions | Unpublished | |
OMIM Online inheritance in man. More detailed clinical information is provided in the supplementary table.