# A Clinical-Based Diagnostic Approach to Cerebellar Atrophy in Children
## 3 Results  
The diagnostic rate in the original 80-patient cohort was 65%. The distribution of diagnosis is shown in Figure 1. Of the 52 patients, a genetic confirmation was obtained in 79% (41/52). The patients lacking a molecular diagnosis include three CDG patients who have a confirmed Pattern I at the T-IEF (in two of them, brothers, a single mutation in ALG9 was found), two with Cockayne, who only have confirmation on fibroblasts, and six patients with urinary OA alterations and/or mitochondrial studies alterations in which the molecular cause is missing despite extensive genetic analyses. Figure 1: Distribution of diagnosis in the 52-patient cohort. Abbreviations legend: ARACS: Autosomal Receive Spastic Ataxia of Charlevoix-Saguenay; CDG: Congenital Disorders of Glycosion; CMT: Charcot-Marie-Tooth; HLD: Hypomyelinating Leukodystrophies; NBIA: Neurodegeneration with Brain Iron Accumulation; NCL: Neuronal Ceroid Lipofuscinosis; PCH: Ponto-Crebellar Hypoplasia; SCA: SpinoCerebellar Ataxias. In the 52-patient cohort, the male to female ratio was 0.68 (M 21/F 31). Age at first diagnosis ranged from 3 months (3 m) to 13 years and 3 months (13 y5 m), with a mean of 5 y4 m and a median of 4 y6 m.  
Table A1 summarizes the prevalence of the main clinical findings, while Table A2 lists the neurophysiological and laboratory exam results; complete data about personal information, clinical features, and exam results are reported in Supplementary Material, Table S1. Growth parameters are shown in Figure 2; most patients have poor growth, with approximately a third being under -2 Standard Deviations (SDs) for Height (H), Weight (W), and Head Circumference (HC); only 25% of the patients show parameters with positive SD values (\(\geq\)0 SD). Microcephaly is present in 35% (18/52); in six patients, the head size reduction is proportional to their short stature, with a H/HC discrepancy lower than 1 SD, while in 12 a more prominent slowdown of the HC is found. Absolute macrocephaly is never observed, but 21% (11/52) have relative macrocephaly. Height is below the normal age range in 35% (18/52) of the children, and in 61% (11/18) of the cases it is associated with poor weight; two children gained weight after a Percutaneous Endoscopic Gastrostomy (PEG) was performed (the QARS1 patient and one of the seven SCA subjects). Facial dysmorphisms are present in 58% of children from almost all categories of disorders, except for Autosomal Recessive Spastic Atoxia of Charlevoix-Saguenay (AR-SACS), Friedreich Ataxia (FRDA), mitochondrial disorders, and NCL. Almost a third of children (16/52) present somatic malformations, which are in most cases skeletal deformities (75%), while heart and genito-urinary abnormalities are rare; eye malformations are limited to Gillespie syndrome, with 2/2 patients showing pathognomic aniridia (see Supplementary Material, Table S1 for details)  
Consistently with the cerebellar dysfunction, a gait and/or appendicular ataxia is present in 80% of patients able to fulfill the examination tasks (35/44); in eight patients, the presence of ataxia is not assessable, given the severely compromised motor or developmental skills. A total of 27% of patients never acquired the first motor developmental stages (no head/trunk control). Tremor is present in 36% (16 of the 44 patients in which it is possible to explore the sign). Oculomotor abnormalities (apraxia or jerky smooth pursuit) are seen in 63% of the children (31/51, one patient has cortical blindness); this number may not reflect the real incidence, given the poor collaboration of the children. A total of 36% have strabismus (19/52) that is in 79% of cases convergent and in 21% divergent. Of the  
Figure 2: Distribution of Height (H), Weight (W), and Head Circumference (HC) within the cohort. Note that more than 70% of children have global parameters in the lower half of Standard Deviations (SD) and more than 30% are below the normality range for all parameters, especially for H.  
36 children able to speak, more than a half have dysarthria (58%, 21/36).