Table 2.

Workup of patients who remained undiagnosed

Reason of referral	Age	Gender	Genetic tests performed
Peripheral nervous system diseases
Demyelinating polyneuropathy	57 60 62 63	Female Female Male Male	Duplication of the gene encoding peripheral myelin protein-22 (PMP-22, Charcot-Marie-Tooth, type 1A)
Axonal polyneuropathy	50	Male	Hereditary Motor and Sensory Neuropathy panel (102 genes)
Syndactyly and small fiber neuropathy	31	Female	Chromosomal microarray Mutations in the GLA gene, encoding alpha-galactosidase A (Fabry) Mutations in TTR gene, encoding Transthyretin (Hereditary amyloidosis)
Small fiber neuropathy	57	Female	Mutations in the GLA gene, encoding alpha-galactosidase A (Fabry) Mutations in TTR gene, encoding Transthyretin (Hereditary amyloidosis)
Myopathy, mental retardation, dysmorphism (high forehead, prognathism, macroglossia, pectus excavatum, scoliosis)	30	Male	Fluorescence in situ hybridization (FISH) to rule out Velo-Cario-Facial syndrome Trinucleotide repeat (CGG), in the FMR1 gene (fragile X syndrome)
Proximal weakness, myotonia	38	Female	Expansion of a CCTG repeat in intron 1 of the zinc finger protein-9 gene (Myotonic dystrophy type 2)
Myotonia since age 20 without cataract, endocrine or cardiac complications. Hypertrophic calves	38	Female	Mutation in the CLCN1 gene (myotonia congenita)
Central nervous system diseases
Cerebellar ataxia ± pyramidal signs	46 51 61 73 80 82	Female Male Male Female Male Female	Mini panel of 7 genes: CAG trinucleotide repeat expansions in the genes: ataxin 1, 2, 3, 7 (SCA 1, 2, 3, 7) SCA 6 Dentatorubral-pallidoluysian atrophy (DRPLA) GAA trinucleotide repeat expansion in intron 1 of the frataxin gene (Friedreich’s ataxia)
Ataxia and tremor	53 73	Male Male	Trinucleotide repeat (CGG), in the FMR1 gene (Fragile X associated tremor ataxia syndrome)
Spastic paraparesis and mental retardation in two brothers of Iraqi Jewish ancestry	52 56	Male Male	Trinucleotide repeat (CGG), in the FMR1 gene (Fragile X syndrome) OPA3 gene mutation (Costeff syndrome)
Spastic paraparesis with diffuse, peri-ventricular white matter changes on brain MRI	56	Female	Exome sequencing
Cerebral small vessel disease	34 48	Female Female	Mutations in the GLA gene, encoding alpha-galactosidase A (Fabry) Mutation in the NOTCH3 gene (CADASIL—cerebral arteriopathy autosomal dominant with subcortical infarcts and leukoencephalopathy)
Generalized dystonia	19 24	Male Male	Mutation in the TOR1A gene, encoding the ATP-binding protein torsin-A, after returned negative: Dystonia gene panel: 38 genes
Spastic paraparesis	33	Female	Hereditary spastic paraparesis panel (78 genes)
Chorea	54 54	Female Male	Trinucleotide repeat (CAG), in the HTT gene (Huntington's chorea)
Spastic paraparesis and peripheral neuropathy	40	Female	Exome sequencing