Palmar Creases Research Articles

Costello syndrome

Costello syndrome is a rare, distinctive, multiple congenital anomaly syndrome, characterized by soft, loose skin with deep palmar and plantar creases, loose joints, distinctive coarse facial features and skeletal and cardiac abnormalities. The affected patients have a predisposition to develop malignancy, developmental delays and mental retardation. Recently, a 7-year-old male child born to normal nonconsanguineous parents presented to us with abnormal facial features, arrhythmia, mitral valve dysfunction and growth retardation. His cutaneous examination revealed lax and pigmented skin over hands and feet with deep creases, acanthosis nigricans and short curly hairs. Its differentiation from other syndromes with similar clinical features is discussed in this article.

Costello syndrome: three sporadic cases

Costello syndrome (CS) is a rare multiple congenital abnormality syndrome characterized by a typical coarse face, developmental delay, psychomotor and growth retardation, neurologic abnormalities, cardiac and cutaneous anomalies, severe feeding difficulties with postnatal growth failure, and increased risk of tumors. Since Costello first described it in 1971 and again in 1977, over 100 cases have been reported worldwide. It was recently shown that CS is a congenital condition caused by heterozygous de novo missense mutations affecting the codon for glycine 12 or 13 of the HRAS gene. We experienced three unrelated cases with coarse faces, developmental delays, short statures, macrocephaly, and redundant skin with deep palmar and plantar creases, hypertrophic cardiomyopathy and atrial tachycardia, which are characteristic of CS.

Multiple primary tumors associated with chromosome 9p deletion

Multiple primary tumors associated with chromosome 9p deletion

Accuracy of the Diagnosis of Physical Features of Fetal Alcohol Syndrome by Pediatricians After Specialized Training

Accurate and early diagnosis of the fetal alcohol syndrome is important for secondary prevention, intervention, and treatment, yet many pediatricians lack expertise in recognition of the characteristic features of this disorder. After a structured training program for pediatricians, we examined the ability to accurately diagnose fetal alcohol syndrome. Two dysmorphologists conducted a 2-day training program in the diagnosis of the physical features of fetal alcohol syndrome for 4 pediatricians in Moscow. Dysmorphologists and pediatricians worked in teams to examine children, demonstrate techniques, and validate that pediatricians could identify physical features of this disorder under direct observation. Subsequently, pediatricians independently evaluated children in 41 boarding schools and orphanages. Those children diagnosed with fetal alcohol syndrome or deferred (possible fetal alcohol syndrome) by the pediatricians were then evaluated by the dysmorphologists. Accuracy of the diagnosis of fetal alcohol syndrome or deferred was assessed, as well as the interrater agreement for specific selected features of the disorder. A total of 110 children were examined by both the pediatricians and the dysmorphologists. Of these, 79 were identified with fetal alcohol syndrome by the pediatricians; in 66 (83.5%) of these children, the diagnosis was confirmed by the dysmorphologists. Among 31 children who were classified as deferred by the pediatricians, 21 (67.7%) were confirmed with either fetal alcohol syndrome or deferred by the dysmorphologists. With respect to selected structural features characteristic of fetal alcohol syndrome, good interrater agreement was noted for height and head circumference < or = 10th centile, whereas moderate-to-fair agreement was noted for smooth philtrum, long philtrum, presence of "hockey-stick" palmar crease, and palpebral fissure length < or = 10th centile. Poor agreement was noted for thin upper lip. After a relatively short training session, pediatricians were reasonably accurate in diagnosing fetal alcohol syndrome on the basis of physical features and in recognizing most of the selected specific features associated with the disorder.

The role of genetic inheritance in the development of palmar creases

The role of genetic inheritance in the development of palmar creases

Familial occurrence of multiple pterygium syndrome: Expression in a heterozygote of the recessive form or variability of the dominant form?

We report on a case with apparently familial multiple pterygium syndrome (MPS). The proposita was a 3-year-old girl with classical symptoms of MPS. A careful clinical examination of the father disclosed the presence of few minor signs of the syndrome, including difficulty in opening the mouth widely, scoliosis, pectus excavatum, hands with slight cutaneous syndactyly, and bilateral single palmar creases. The radiograph of the hands disclosed malformed carpal bones and an altered metacarpal-phalangeal pattern. The father shows limited symptoms, which has been reported before in the autosomal dominant form of MPS. However, it is also possible that he is showing a heterozygous state of the autosomal recessive form of MPS. In conclusion, we emphasize the importance of examining accurately the parents of a child who has classical MPS phenotype, even those with normal stature and an absence of facial anomalies.

The effect of gabapentin in earlier stage of reflex sympathetic dystrophy

The objective of this paper is to investigate the effect of gabapentin in the earlier stage of reflex sympathetic dystrophy syndrome (RSD). Twenty-two patients diagnosed with RSD were enrolled. Initial gabapentin dosage was 600 mg/day. This dosage is increased gradually until a satisfactory pain level was reached. After this level, this dosage was maintained throughout the study. An exercise program was also applied to the patients. Provoked and static pain scores of the patients were obtained initially, at 3-day intervals for maintenance dosage determining, and at 6 weeks after the discharge. Functional improvement parameters were volumetric measurement; dynamometric measurement and third finger pulp-distal palmar crease distance measurement for hands; and metric circumferential measurement and range of motion for elbow, knee, and foot initially, at baseline, on the tenth day, upon discharge, and 6 weeks after the discharge. The mean maintenance dose of gabapentin was 1,145.46+/-377.6 mg/day (range, 900-1,800 mg/day). Improvements in spontaneous and provoked pain intensities were statistically significant. No statistically significant difference was obtained in functional improvement parameters. Dizziness in three patients, headache in two patients, and mild burning feeling in the tongue in one patient were the reported side effects. These symptoms resolved spontaneously in few days. Gabapentin cannot be recommended as the drug of choice, but it may be considered as one of the therapeutic alternatives in the management of pain due to RSD. We suggest that it is effective only for the pain and not for other symptoms of RSD. Serious side effects that will cause the patient to stop using the drug are rare.

Addison's disease

Addison's disease, or primary adrenal insufficiency, results in glucocorticoid and mineralocorticoid deficiency. Orthostatic hypotension, fever, and hypoglycemia characterize acute adrenal crisis, whereas chronic primary adrenal insufficiency presents with a more insidious history of malaise, anorexia, diarrhea, weight loss, joint, and back pain. The cutaneous manifestations include darkening of the skin especially in sun-exposed areas and hyperpigmentation of the palmar creases, frictional surfaces, vermilion border, recent scars, genital skin, and oral mucosa. Measurement of basal plasma cortisol is an insensitive screening test. Synthetic adrenocorticotropin 1-24 at a dose of 250 μg works well as a dynamic test. Elevated plasma levels of adrenocorticotropin and renin confirm the diagnosis. Treatment involves replacement of the deficient hormones.

Epilepsy and deletions at chromosome 2q24

Chromosomal abnormalities are an important cause of epilepsy [Singh et al., 2002], which might be the presenting symptom in the context of a specific syndrome. A recent article by Langer et al. [2006] reports on a translocation t(2;15) with deletion at 2q24-q31 in a girl with epilepsy, dysmorphic features, and severe developmental delay. As this case adds to the growing list of severe epilepsy associated with deletions at chromosome 2q, it deserves complementary information and comments. We would like to point out that wedescribed a very similar case in a previous report on a girl carrying a deletion at chromosome 2q24 [Pereira et al., 2004]. In our patient as well as in the patient described by Langer et al. [2006], epileptic seizures first started early in life, at 2 and 3 months 1/2, respectively. Seizures were frequent in both cases and were accompanied by severe apnea. Both children had severe developmental delay and no speech development. In the two patients, additional common features were encountered, including microcephaly, downslanting and small palpebral fissures, and abnormal ears. Despite the clear similarities existing between those two cases, other clinical manifestations were not shared in common by the two patients. Our patient had single palmar creases bilaterally and partial syndactyly between the 2nd and 3rd toes, and cardiac examination showed a small interventricular communication. In contrast, the patient in Langer et al. [2006] had micrognathia, blepharophimosis, hypertelorism, and coloboma of the iris and retina. This is reminiscent of the clinical features described in other cases of del(2)(q31q33) [Ramer et al., 1990] and del(2)(q24–q31) [Nixon et al., 1997]. The size and the boundaries of the respective deleted areas vary from one patient to another (Fig. 1) and this might well explain the clinical differences described above. In the case of the patient described by Langer et al. [2006], the translocation breakpoint at 15q14 might also participate in the phenotype. In this latter patient, the deleted region on chromosome 2 spans about 13 Mb between markers rs198688 and rs1399959 and contains up to 76 genes including SCN1A and SCN2A, the mutations of which have already been associated with various epileptic syndromes [Meisler and Kearney, 2005]. Our critical region was of smaller size and spanned3–7Mb [Pereira et al., 2004] (Fig. 1). It is fully included within the 13 Mb-deleted area described by Langer et al. [2006] (Fig. 1) and ‘only’ contains 32 genes at most and 10 genes at least, including SCN1A and SCN2A as well as three other sodium channel genes (see the human genome sequence at UCSC web site: http://genome.ucsc. edu) [Pereira et al., 2004]. Epilepsy was not seen in the patient reported by Nixon et al. [1997]. The data reported by Langer et al. [2006] thus reinforce our previous hypothesis [Pereira et al., 2004], that the epileptic phenotype in these patients is specifically associated with the deletion of the genomic area comprised between marker D2S354 (marker d in Fig. 1) and marker D2S2345 (h) at most. This genomic region actually comprises the cluster of five sodium channel genes mentioned above. As already discussed [Pereira et al., 2004; Langer et al., 2006], the seizures in the affected children might well be due to loss or haploinsufficiency of one or several of these genes. Such deletion events might remain undetected and hence might be

Personal observation of skin disorders in malnutrition

This is a description of some unknown skin disorders found by a physician inmate in a concentration camp, 1958 to 1962. After prolonged semistarvation and ultraheavy physical labor, skin lesions developed among the inmates including cutaneous pigmentation overlying bony prominence, buccal membrane pigmentation, palmoplantar keratoderma with fissures, palmar crease clefts, nail layering, intra-nail hemorrhage, and so on. These lesions responded dramatically to nutrition therapy, including dietary improvement, yeast administration, or thiamin injection. Thiamin deficiency was confirmed to be one of major etiologic factors, whereas the deficiency of niacin or riboflavin also played a part. In the pediatric case with palmar crease clefts, both thiamin and niacin were dramatically effective. No laboratory data could be provided.

Efficacy of a Percutaneous A1 Pulley Release Technique With Identification of Anatomic Differences Between Genders

This cadaver study investigates the efficacy and safety of the Biomet knife and technique for percutaneous A1 pulley release. We also evaluate the anatomic relationship between specific palmar surface landmarks and relevant underlying structures and identify differences between genders. Eighty percutaneous A1 pulley releases, excluding the thumb, were performed on 20 fresh human cadaver hands (10 male, 10 female). Complete release was obtained in 60 of 80 fingers. Success rates for each surgeon improved markedly as the study progressed. There were no significant differences between males and females regarding the distance between a standardized incision site and the proximal edge of the A1 pulley. A learning curve exists for percutaneous A1 pulley release using the Biomet knife and technique. The extended distal palmar crease is a reasonable incision site for percutaneous release of the index, middle, and ring A1 pulleys in both men and women as the A1 pulley begins just distal to this surface landmark.

CDG: a new case of a combined defect in the biosynthesis of N- and O-glycans

We report on a 5.5-year-old boy with a multiple malformation syndrome and biochemical abnormalities suggesting a combined defect in the biosynthesis of Nand O-glycans. The patient was followed prenatally for intrauterine growth retardation and a finding of intestinal obstruction (double bubble sign). Born full term as the first child of healthy, non-related Czech parents without remarkable family history, his Apgar scores were 6, 6, and 7; birth weight 2,310 g; body length 45 cm; and head circumference 32.5 cm. He presented with dysmorphic features, including dolichocephaly, low hairline, high nasal bridge, thin lips, small chin, gothic palate, blepharophimosis and epicanthus, in addition to other malformations, such as arachnodactyly, unusual palmar creases, sinus sacralis, pes equinovarus, hypospadias, inguinal hernia, cryptorchidism, vesicoureteral reflux, peripheral pulmonary stenosis, and patent foramen ovale. Shortly after birth a surgical correction of intestinal malrotation and duodenal stenosis (Ladd’s syndrome) was done. Neonatal brain ultrasonography, ophthalmologic examination, a skeletal survey and an electrocardiogram were normal. Chromosome analysis was normal. Laboratory tests including serum lactate, ammonia, and immunological investigations were within normal limits. Serum biotinidase, plasma and urinary amino acids, organic acids, purines and pyrimidines, sugars, oligoand mucopolysaccharides did not reveal any pathological changes. At age 4 months, the brain ultrasonography showed hypogenesis of the posterior part of the corpus callosum (later confirmed by MRI), and abnormal EEG delta waves were noted occipitally, without epilepsy. In addition to anemia (90 g/l, normal 105–135), elevated LDH (12.7 μkat/l, normal< 4.4) and elevated transaminases (1.1–2.2 μmol/l, normal<0.8), prolonged values of APTT (39.3–45.6, normal range 31.8–35.0) and PT (13.3, normal 11.7) were found; antithrombin III and CK were within the physiological range. At 3.5 years, the boy was admitted to hospital with severe laryngopharyngitis, and at that time a screening for congenital disorders of glycosylation (CDG) was performed. Isoelectric focusing (IEF) and HPLC of serum transferrin (Tf) showed a slight increase in asialo-Tf (4.0%; reference interval, 0.0–3.0%), a marked increase in disialoTf (18.7%; reference interval, 2.5–9.8%), increased trisialo-Tf (17.8%; reference interval, 3.4–13.7%) and decreased tetrasialo-Tf (38.8%; reference interval, 43.7– 68.1%). Abnormalities of alpha1-antitrypsin (aAT) and thyroxin-binding globulin pointed to a generalised defect Z. Albahri . E. Marklova . P. Dědek Department of Pediatrics, Faculty of Medicine, Charles University, Hradec Kralove, Czech Republic

References to avoid complications in releases of the trigger thumb: a cadaveric study

The aim of this cadaveric study was to demonstrate the utility of some visible landmarks in the hand in avoiding probable complications during percutaneous or open releases performed for the trigger thumb associated with flexor tendon tenosynovitis. In this cadaveric study, we dissected 20 thumbs of 10 fresh cadavers (10 males; mean age 46 years; range 31 to 62 years) from the interphalangeal to the metacarpophalangeal creases to expose all digital arteries, nerves, the flexor tendon, and the A1 pulley. The following distances were measured: from the proximal edge of the A1 pulley to the digital arteries and nerves, and to the interphalangeal and metacarpophalangeal creases of the thumb. The proximal edge of the A1 pulley lies at a mean distance of 3.5 mm distal to the metacarpophalangeal crease, and about 35 mm distal to the interphalangeal crease. These values may be helpful during percutaneous releases in avoiding any injury to the radial digital nerve, which crosses the flexor tendon proximal to the A1 pulley. On the other hand, care should be taken for the ulnar digital nerve during open releases, which is at a higher risk than the radial digital nerve due to its closer proximity to the A1 pulley, the mean distances being 1.95 mm and 3.40 mm, respectively. These data are helpful in avoiding injuries to the digital nerves, which imply that the digital nerve on the ulnar side of the A1 pulley is more vulnerable during open releases, while the radial digital nerve proximal to the metacarpophalangeal crease is more vulnerable during percutaneous attempts. Complications can be avoided if the interphalangeal and palmar creases are taken into consideration.

Male Pseudohermaphroditism Caused by an Inborn Error in Cholesterol Biosynthesis: Smith-Lemli-Opitz Syndrome

Smith-Lemli-Opitz syndrome is an autosomal recessive disorder caused by mutations of 3? -hydroxysterol –? 7reductase gene (DHCR7) which maps to 11q12-13 and was the first discovered defect in cholesterol biosynthesis resulting in a congenital dysmorphology syndrome. We present the case of a 46,XY newborn with ambiguous genitalia and multiple congenital anomalies (atrial septal defect, ventricular septal defect, syndactyly of the second and third toe, cleft palate, webbed neck, small fontanels, mesomelia, simian palmar crease, micrognathia, wide nasal bridge with anteverted nostrils, low set ears). Hormonal assessment performed at twelve days revealed a decreased testosterone level (0.03 ng/mL), a high estradiol level (448.8 pg/mL), normal LH (2.8UI/mL), DHEAS (86.61ig/dL), progesterone (1.34ng/mL) and 17 hydroxyprogesterone (1.08ng/mL) levels. Cholesterol was low (44mg/dL) confirming the diagnostic of Smith-Lemli-Opitz syndrome.

Pseudotrisomy 13 syndrome: a case with left ventricular hypoplasia and duodenal stenosis

We report a case of a female child born at 32 weeks of gestation. Birth weight was 1200 g (<3rd centile), length 40 cm (10th-50th centile) and head circumference 23.5 cm (<3rd centile). Clinical examination revealed microcephaly, hypotelorism, microphthalmia, a flat rudimentary nose with a single nasal cavity, high palate, thick dysplastic low-set ears, a short neck, postaxial polydactyly of the upper limbs, and single palmar creases. Investigations showed alobar holoprosencephaly, absence of the third ventricle and midline structures of the brain, microphthalmia, hypotelorism, left ventricular hypoplasia, a large atrial septal defect, and duodenal stenosis. The karyotype was 46,XX. A hypoplastic left ventricle and duodenal stenosis have not been previously reported in pseudotrisomy 13 and this case might aid in the further delineation of this syndrome.

Fetal alcohol spectrum disorders in Finland: Clinical delineation of 77 older children and adolescents

The adverse effects of alcohol on the developing human comprise a spectrum of structural anomalies and behavioral and neurocognitive disabilities, most accurately termed fetal alcohol spectrum disorders (FASD). We previously have proposed revisions to the 1996 Institute of Medicine Diagnostic Criteria for diagnoses in the FASD continuum [fetal alcohol syndrome (FAS), partial fetal alcohol syndrome (PFAS), alcohol related birth defects (ARBD), and alcohol related neurodevelopmental disorder (ARND)], allowing for more reproducible and accurate FASD diagnosis in a clinical setting [Hoyme et al., 2005]. The NIAAA recently has coordinated and funded an international consortium of projects aimed at more complete characterization of the teratogenic spectrum of alcohol. One of the projects sites is in Finland. The aims of this project are: (1) to completely clinically characterize the structural and learning/behavioral phenotypes of a large cohort of older children and adolescents with moderate to severe disability within the FASD continuum; (2) to correlate FASD dysmorphology and behavioral phenotypes with CNS structure and function (i.e., MRS, MRI correlations); (3) to compare the phenotype of a genetically homogeneous population of Finnish children with FASD to that observed in other populations. We have recently completed dysmorphology examination and parent/guardian interviews of the 77 children in the Finnish cohort. The purpose of this report is to present historical and morphometric data on these patients, thereby more completely delineating the clinical spectrum of FASD in older children and adolescents, contrasting the phenotype with that described in other populations and examining whether a weighted dysmorphology score could be used as a clinical and research adjunct when fetal alcohol exposure is being suspected. All children were previously diagnosed with FASD by an experienced pediatric specialist in Finland, and all were exposed to significant maternal alcohol abuse prenatally. The sex ratio of the cohort was 0.38 (male: female) and ages ranged from 8 to 20 years, with a mean of 13 years. After application of the Revised IOM Diagnostic Criteria, 53% of the subjects were diagnosed as having FAS, 30% PFAS, 12% ARND, and 5% other diagnoses. Of note, although a family history of mental retardation or birth defects was rare, 43% of the children had one or more sibling who also carried a diagnosis of FAS. Eighty-nine percent of the mothers smoked cigarettes during gestation; other teratogenic exposures were rare. Almost none had undergone genetics evaluation in the past. Almost all of the subjects had resided in multiple foster placements since early childhood and had been followed regularly by pediatric specialists. Although 11% were born prematurely, 70% demonstrated prenatal growth deficiency, and 45% were microcephalic. Other than growth deficits and the cardinal facial features, the most common major and minor anomalies noted were: camptodactyly (55%), "hockey stick" or other altered palmar creases (51%), refractive errors (40%), strabismus (38%), dental crowding (43%), nail hypoplasia (38%), GU anomalies (22%), and congenital heart defects (18%), "Railroad track" ears were not observed in this population.

Discrete Finger and Palmar Feature Extraction for Personal Authentication

A practical method for a noncontacting and real-time feature extraction for personal authentication is proposed. The finger geometry and feature extraction of the palmar flexion creases are integrated into a small number of discrete points based on the anatomical observation. For a video image of either palm, a palm placed freely facing toward a video camera is acquired. The fingers are brought together, and the palm is straightened out to eliminate any constraints. The discrete feature points for the fingers involve intersection points of the three finger (digital) flexion creases on the four finger skeletal lines. The feature points for the palm involve intersection points of the major palmar flexion creases and/or prominent creases of the palm on the extended finger skeletal lines. The orientations of the creases at the intersection points are also extracted features to be matched. The matching results are perfect for about 500 palm samples from 50 subjects so far. This discrete point processing, requiring no time-consumptive palmprint image analysis and requiring less than one second processing time, will contribute to a noncontacting, real-time and reliable feature extraction, easily combinable with other traits, for the personal authentication.

Les anomalies morphologiques mineures dans la schizophrénie : étude d'une population tunisienne

Minor physical anomalies are slight dysmorphic features representing subtle alterations in the development of various bodily structures in the mouth, eye, ear, head, hand, and feet areas. The aim of this study was to assess the frequency and the type of minor physical anomalies in patients with schizophrenia in a Tunisian population. One hundred adult patients (67 men, 33 women, mean age : 38 years (S.D = 10.6), mean age of onset : 24.1 years (S.D = 6.5), educational level : 8 years (S.D = 4.7)) and 143 comparison subjects (95 men, 48 women); mean age : 42.8 years (S.D = 16.6), educational level: 5.7 years (S.D = 4.7) were assessed by using Gourion's scale which consists of 41 minor physical anomalies. The total score in patients with schizophrenia (mean: 1.7, S.D = 1.34) was significantly high than in healthy subjects (mean : 1.2, S.D = 1.06). The cut-off score that optimally discriminated the patients from comparison subjects (maximizing sensitivity and specificity for schizophrenia) was two or more. A score of two or more classified 51% of the patients and 64.3% of the comparison subjects. A higher rate of minor physical anomalies was more specific and rare. Patients showed a higher rate for 20 anomalies, the differences reaching statistical significance for six of them : asymmetric ears (Patients: 5%, Controls: 0%), curved fifth finger (Patients: 7%, Controls: 0.7%), syndactily (Patients: 5%, Controls: 0%), gap between first and second toe (Patients: 12%, Controls : 2.1%), overlapping toes (Patients: 8%, Controls: 1.4%) and asymmetric feet (Patients: 7%, Controls: 0.7%). Nine anomalies were less frequent in patients and only one reached statistical significance : palate anomalies (Patients: 7%, Controls: 17.5%). Twelve anomalies were absent in both groups (large nose basis, facial asymmetry, ptosis, coloboma, low seated ears, furrowed tongue, cleft lip, abnormal palm creases, overlapping fingers, small fingernails, asymmetric hands and hyper-convex toenails). The total score was significantly correlated with the age of onset ( R = –0.21, P = 0.03) but not with illness severity (CGI score and number of hospital admissions / duration of illness). Reviewing results of similar studies in other populations, Tunisian patients with schizophrenia seem to have fewer minor physical anomalies. Only three significant frequent anomalies were concordant with results of one another study (curved fifth finger, syndactily and gap between 1 st and 2 nd toe). This large heterogeneity might be explained by ethnic variability. More studies are needed.

Type III hyperlipoproteinemia with xanthomas and multiple myeloma

Type III hyperlipoproteinemia usually results from an inherited defect in the composition of apolipoprotein E and is associated with atherosclerosis. An acquired form of the type III phenotype may rarely be associated with myeloma and immunoglobulin-lipoprotein complexes. We present the case of a 72-year-old man with a history of well-controlled, unclassified hypercholesterolemia and hypertriglyceridemia, without evidence of atherosclerotic disease. He subsequently developed refractory dyslipidemia, palmar crease, and tuberous xanthomas. Type III hyperlipoproteinemia was confirmed, and nonclassic defective apolipoprotein E. Common secondary causes of hyperlipidemia were ruled out. A workup for malignancy revealed monoclonal IgA gammopathy. Immunostaining confirmed IgA antibodies complexed to the patient's very low-density lipoprotein (VLDL) fraction, causing gross impairment of VLDL metabolism. Conventional therapy for type III hyperlipoproteinemia was attempted but ineffective. Thus, chemotherapy was initiated for his myeloma, with subsequent lowering of his IgA, cholesterol, and triglyceride levels, and improvement of his xanthomas. There are several unusual features to this case. Planar xanthomas can be associated with myelomas, but usually in the setting of normal lipids. Type III hyperlipoproteinemias are not usually refractory to standard therapy and are only rarely associated with IgA myeloma. IgA antibodies complexed to the patient's VLDL caused gross impairment of VLDL metabolism. The patient's apolipoprotein E genotype (heterozygote E2/E3) is not typical for expression of the heritable type III phenotype (homozygote E2/E2). These features support a causal relationship between this patient's multiple myeloma and type III hyperlipoproteinemia rather than two independent, coexistent conditions.

Dysbetalipoproteinemia and Clomipramine

Back to table of contents Previous article Next article Letter to the EditorFull AccessDysbetalipoproteinemia and ClomipramineDANIEL T. HOLMES, M.D., PHILLIP LONG, M.D., and JIRI FROHLICH, M.D., DANIEL T. HOLMESSearch for more papers by this author, M.D., PHILLIP LONGSearch for more papers by this author, M.D., and JIRI FROHLICHSearch for more papers by this author, M.D., Vancouver, B.C., CanadaPublished Online:1 Jul 2005https://doi.org/10.1176/appi.ajp.162.7.1384-aAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Approximately 1% of North Americans and Northern Europeans are homozygous for apolipoprotein-E2 (APOE-2) (1). However, overt hyperlipoproteinemia occurs in only 2%–10% of these people, resulting in a markedly increased risk of atherosclerosis (1). There are numerous environmental factors known to precipitate hyperlipoproteinemia in APOE-2 homozygotes. These include the coexistence of other genetic dyslipidemias, hypothyroidism, diabetes mellitus, menopause, alcohol, poor diet, and obesity (1). Although protease inhibitors have been observed to precipitate dysbetalipoproteinemia (2), there are no such reports implicating tricyclic antidepressants. However, mild (3, 4) to moderate (5) increases induced by tricyclic antidepressants in total cholesterol have been observed in the general population with these medications.Mr. A, a 48-year-old man with major depressive disorder, was referred to our clinic for severe dyslipidemia. At the time, he was not taking lipid-lowering medications. For most of the previous 20 years, he had been taking the tricyclic antidepressant clomipramine, first at 75 mg/day and then at 150 mg/day. Attempts to control his symptoms with selective serotonin reuptake inhibitors had failed. His other medications were carbamazepine, 200 mg t.i.d., and clonazepam, 1.5 mg at bedtime.Mr. A’s family physician had described his initial lipid elevations as “moderate” and discovered them about 5 years after the initiation of clomipramine. However, the increase to 150 mg/day resulted in severe dyslipidemia: a total cholesterol level of 694.9 mg/dl, a triglyceride level of 637.2 mg/dl, a high-density lipoprotein cholesterol level of 81.1 mg/dl, and a total cholesterol/high-density lipoprotein cholesterol ratio of 8.6. Of interest, before his referral, Mr. A had implicated clomipramine by discontinuing it under his psychiatrist’s supervision. Dramatic improvements were observed after 11 days. His total cholesterol level was 338.2 mg/dl, his triglyceride level was 210.6 mg/dl, his high-density lipoprotein cholesterol level was 51.0 mg/dl, his low-density lipoprotein cholesterol level was 245.6 mg/dl, and his total cholesterol/high-density lipoprotein cholesterol ratio was 6.6.Within weeks, Mr. A’s depressive symptoms returned, and clomipramine was reinitiated, again causing severe dyslipidemia. The lipid-raising effect of clomipramine was observed both with and without co-administration of carbamazepine, implicating the tricyclic antidepressant alone. Mr. A’s levels of thyroid-stimulating hormone and fasting glucose were normal. His medical history was negative for diabetes mellitus, renal, and hepatic disease, excessive alcohol intake, and obesity. Although his father had had minor increases in total cholesterol, there was no family history of coronary heart disease, peripheral or vascular disease, or stroke among first-degree relatives.Mr. A’s physical examination was unremarkable except for the presence of palmar xanthomas, pathognomonic of dysbetalipoproteinemia (type III hyperlipoproteinemia). He had first noticed the orange discoloration of his palmar creases 4 years after starting clomipramine but was unaware of its significance. Genetic testing confirmed APOE-2 homozygosity. Since lovastatin had previously failed to improve his lipid levels, fenofibrate, 160 mg/day, was prescribed. Unfortunately, his mood soon began to deteriorate, and he had increased frequency of suicidal ideation. Thus, although it was unclear that fenofibrate was the cause, we elected to discontinue it. Atorvastatin, 40 mg/day, was then prescribed. Subsequently, his lipid levels were somewhat improved: his total cholesterol level was 517.4 mg/dl, his triglyceride level was 460.2 mg/dl, his high-density lipoprotein cholesterol level was 57.9 mg/dl, and his total cholesterol/high-density lipoprotein cholesterol ratio was 8.9. Of interest, Mr. A complained of a depressed mood while taking atorvastatin, also necessitating its discontinuation. He recently started taking ezetimibe for lowering his lipid levels.We suggest that the use of tricyclic antidepressants may induce dysbetalipoproteinemia in APOE-2 homozygotes. Appropriate referral and APOE genotyping should be considered for patients discovered to be dyslipidemic while taking tricyclic antidepressants.