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We reviewed 45 children with cerebellar hypoplasia on magnetic resonance imaging to identify clinical features associated with cerebellar hypoplasia. We then studied children presenting with any likely associated clinical feature of cerebellar hypoplasia previously observed or reported. Two hundred fifty-one children, with one or more of these features, exhibited no cerebellar hypoplasia on imaging. We compared the children with cerebellar hypoplasia with those without cerebellar hypoplasia. Logistic regression and Pearson's chi(2) test were used. Of the 45 children with cerebellar hypoplasia, 39 exhibited developmental delay; 24, speech delay; 25, seizures; nine, microcephaly; 22, hypotonia; 22, ataxia and impaired coordination; four, abnormal movements (tremor or titubation); 13, hypertonia; eight, autistic features; and 18, ocular signs (nystagmus, strabismus, and abnormal ocular movements). Statistically significant clinical features of children with cerebellar hypoplasia compared with those without were development and speech delay, microcephaly, abnormal movements, ataxia and impaired coordination, autistic features, hypotonia, and ocular signs. The regression combination of speech delay, ataxia, hypotonia, autistic features, and ocular signs correctly predicted 86% of those with cerebellar hypoplasia. Main clinical features of cerebellar hypoplasia are developmental or speech delay, autistic features, ataxia, hypotonia, and ocular signs.

Sporadic nonsyndromic cerebellar hypoplasia is a radiological diagnosis with clinical features and a relation with developmental disability that are presently not known. Through a retrospective review of a comprehensive standardized computerized database containing more than 2,500 patients examined consecutively by a pediatric neurologist, 11 with nonfamilial, nonsyndromic cerebellar hypoplasia on neuroimaging (CT and/or MRI) were identified. With the exception of two patients, all had been originally referred during infancy or the preschool years for assessment of a developmental disability. All 11 had "cerebellar" findings on initial examination and five were microcephalic; three others were below the 10th percentile. All exhibited developmental disability, commonly of mild to moderate degree. Motor involvement predominated, often involving fine motor skills more than gross motor functions. Imaging consistently disclosed vermis hypoplasia with additional supratentorial cerebral dysgenesis in one child and cerebellar hemispheric hypoplasia in another. Cerebellar hypoplasia is a developmental anomaly that appears to be either etiologically related to, or a marker for, developmental disability, thus confirming the intact cerebellum's integral role in normal psychomotor development. This series suggests that cerebellar hypoplasia should be considered in the young child presenting with developmental delay with prominent motor involvement, together with cerebellar signs and/or microcephaly.

Fetal Cytomegalovirus (CMV) infection in early pregnancy usually results in severe neurological handicap and sensorineural hearing loss with typical neuroradiological findings of calcification, migrational anomalies, disturbed myelination, and cerebellar hypoplasia. Infections acquired in late pregnancy have less prominent signs, such as microcephaly, hearing deficits, and minor neurological handicap. We report 7 children who presented with a similar clinical complex of signs: microcephaly, sensorineural hearing impairment, behavior problems with hyperactivity, reduced apprehension for pain in 5 of the 7, ataxia in 3, and hypotonia with clumsiness in 3 others. All manifested mild to severe developmental problems. Cranial CT revealed calcification in 4 of 6 patients. MRI in all 7 children showed patchy to confluent nonprogressive dysmyelination. Only 2 children had acute neonatal signs of congenital CMV infection. We assume that these children acquired CMV infection in the third trimester of gestation, leading to microcephaly, hearing loss, and neurological and developmental problems with typical neuroradiological signs.

Background Hoyeraal-Hreidarsson syndrome is a dyskeratosis congenita–related telomere biology disorder that presents in infancy with intrauterine growth retardation, immunodeficiency, and cerebellar hypoplasia in addition to the triad of nail dysplasia, skin pigmentation, and oral leukoplakia. Individuals with Hoyeraal-Hreidarsson syndrome often develop bone marrow failure in early childhood. Germline mutations in DKC1, TERT, TINF2, RTEL1, ACD, or PARN cause about 60% of individuals with Hoyeraal-Hreidarsson syndrome. Patient Description We describe 14 years of follow-up of an individual with Hoyeraal-Hreidarsson syndrome who initially presented as an infant with intrauterine growth retardation, microcephaly, and central nervous system calcifications. He was diagnosed with Hoyeraal-Hreidarsson syndrome at age 6 years and had a complicated medical history including severe developmental delay, cerebellar hypoplasia, esophageal and urethral stenosis, hip avascular necrosis, immunodeficiency, and bone marrow failure evolving to myelodysplastic syndrome requiring hematopoietic cell transplantation at age 14 years. He had progressive skin pigmentation, oral leukoplakia, and nail dysplasia leading to anonychia. Whole exome sequencing identified novel biallelic variants in PARN . Conclusions This patient illustrates that the constellation of intrauterine growth retardation, central nervous system calcifications, and cerebellar hypoplasia, esophageal or urethral stenosis, and cytopenias, in the absence of congenital infection, may be due to Hoyeraal-Hreidarsson syndrome. Early diagnosis of Hoyeraal-Hreidarsson syndrome is important to optimize medical management and provide genetic counseling.

Spinal muscular atrophies are a clinically and genetically heterogeneous group of disorders. Atypical forms of the disease have also been described, including those with associated sensory deficits, hearing loss, cerebellar hypoplasia, congenital heart defects, arthrogryposis, and bone fractures at birth. The patient described here is a male infant, born to a 30-year-old mother at 34 weeks of gestation complicated with polyhydramnios. The first son of consanguineous parents had died with the same clinical features. The patient required ventilatory support because of respiratory failure after the birth and died on day 13. His physical examination revealed profound generalized hypotonia, absence of deep tendon and neonatal reflexes, dysmorphic facies, arthrogryposis, clinodactyly, and left femur fracture. A muscle biopsy revealed variation in fiber size with occasional hypertrophic fibers. The postmortem examination revealed loss and degeneration of anterior horn cells. We propose that the patient, who presented with severe hypotonia, femur fracture, arthrogryposis, dysmorphic features, history of early death of his brother with the same clinical features and parental consanguinity, had probable X-linked spinal muscular atrophy. However, autosomal-recessive inheritance can not be completely excluded.

The classic features of Marinesco-Sjogren syndrome include bilateral cataracts, cerebellar ataxia, and mental deficiency with an autosomal recessive inheritance pattern. Weakness and a variety of other characteristics are present inconsistently. A limited number of neuroimaging studies have indicated that cerebellar hypoplasia is the most common finding. We report a patient with near normal intelligence, unilateral cataract, and the previously unreported magnetic resonance imaging findings of cerebellar dysplasia, arachnoid cyst, and absent septum pellucidum. A review of the literature suggests significant heterogeneity in the Marinesco-Sjogren syndrome.

Two sisters with autosomal recessive cerebellar hypoplasia and severe nonprogressive retinal pigmentary disease are presented. This syndrome has been previously described in only 1 patient. The retinal changes may be difficult to discern and we suggest that all patients with congenital ataxia have a detailed ophthalmologic assessment, including electroretinography.

A patient with the CHARGE association (Coloboma of the eye, Heart defect, Atresia of the choana, Retarded growth and development, Genital hypoplasia, and Ear anomalies or deafness) had intermittent hyperpnea and cerebellar hypoplasia; therefore, he had both the CHARGE association and Joubert syndrome. The 2 syndromes have not been previously linked. We discuss their similarities and review the literature.