Ataxia-pancytopenia syndrome with SAMD9L mutations.

OBJECTIVE: We describe the neurologic, neuroradiologic, and ophthalmologic phenotype of 1 Swedish and 1 Finnish family with autosomal dominant ataxia-pancytopenia (ATXPC) syndrome and SAMD9L mutations. METHODS: Members of these families with germline SAMD9L c.2956C>T, p.Arg986Cys, or c.2672T>C, p.Ile891Thr mutations underwent structured interviews and neurologic and ophthalmologic examinations. Neuroimaging was performed, and medical records were reviewed. Previous publications on SAMD9L-ATXPC were reviewed. RESULTS: Twelve individuals in both families were affected clinically. All mutation carriers examined had balance impairment, although severity was very variable. All but 1 had nystagmus, and all but 1 had pyramidal tract signs. Neurologic features were generally present from childhood on and progressed slowly. Two adult patients, who experienced increasing clumsiness, glare, and difficulties with gaze fixation, had paracentral retinal dysfunction verified by multifocal electroretinography. Brain MRI showed early, marked cerebellar atrophy in most carriers and variable cerebral periventricular white matter T2 hyperintensities. Two children were treated with hematopoietic stem cell transplantation for hematologic malignancies, and the neurologic symptoms of one of these worsened after treatment. Three affected individuals had attention deficit hyperactivity disorder or cognitive problems. Retinal dysfunction was not previously reported in individuals with ATXPC. CONCLUSIONS: The neurologic phenotype of this syndrome is defined by balance or gait impairment, nystagmus, hyperreflexia in the lower limbs and, frequently, marked cerebellar atrophy. Paracentral retinal dysfunction may contribute to glare, reading problems, and clumsiness. Timely diagnosis of ATXPC is important to address the risk for severe hemorrhage, infection, and hematologic malignancies inherent in this syndrome; regular hematologic follow-up might be beneficial.

Apolipoprotein B as a marker of familial hyperlipoproteinemia.

AIMS: Families with 10-12-year-old schoolchildren were informed about and asked to participate in a study to identify children with hyperlipoproteinemia. We hypothesised that children and families with familial blood lipid abnormalities, specifically those with familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCHL), could be identified by the child's apolipoprotein B level exceeding the 95th percentile. METHODS: Written information and consent was distributed to the families. Families whose child had an apoB concentration exceeding the 95th percentile were further examined. Children and parents were divided into normal, high and very high low density lipoprotein cholesterol (LDLC) groups. In adults a high LDLC level was defined as > 4.1-4.9, a very high as > 4.9 mmol/l, in children as > 3.4-4.1 and > 4.1 mmol/l, respectively. The triglyceride level was regarded as high when > 3.6 mmol/l. RESULTS: Of 2,855 families, 2,186 agreed to participate. The 95th percentile apoB level was for boys 0.98 and girls 1.07 g/l. Of the 131 children with an apoB level above the 95th percentile, 109 families accepted further examinations. Of 109 hyperapoB children 23 were obese. Normal LDLC was found in 28 hyperapo B children of whom six parents had high/very high LDLC and one high triglyceride concentrations. A high LDLC level was found in 52 children of whom 23 parents had higy/very high LDLC and another five high LDLC and/or high triglyceride concentrations. A very high LDLC level was found in 29 children, in two of them due to hypothyroidism, 17 had a parent with high/very high LDLC and another two parents a high triglyceride concentration. Familial hypercholesterolemia, defined as a LDLC concentration above twice the normal one in the child and a very high level in a parent, was suspected in six families, five having a relative with premature CHD. The families with FCHL should be included in the 20 families with hyperapoB and a child with high-very high LDLC and a parent with very high LDLC or TG levels. CONCLUSION: Of the 109 children examined due to the child's increased apoB concentration, about 20% were obese and 75% had an increased LDLC concentration. A familial occurrence of hyperlipoproteinemia was evident in about 50% of the families with an hyperapoB child. Six families probably suffer from familial hypercholesterolemia. The definite number of FCHL families could not be defined since extended pedigrees were not available. A high suspicion of FCHL was evident in 20 families. ApoB is an important marker of hyperlipoproteinemia of familial occurrence identifying families in need of primary CHD prevention.

Glomus tumours in the long finger and in the thumb of a young patient with neurofibromatosis-1 (Nf-1).

Glomus tumours are rare in adults, and such tumours may be associated with neurofibromatosis-1 (Nf-1). Here we describe successful treatment of two glomus tumours initially in the long finger and, one year later, in the thumb in a 17-year young girl with Nf-1.