Type E brachydactyly

About: Type E brachydactyly is a(n) research topic. Over the lifetime, 11 publication(s) have been published within this topic receiving 276 citation(s).

Brachydactyly and Mental Retardation: An Albright Hereditary Osteodystrophy–like Syndrome Localized to 2q37

Abstract: We report five patients with a combination of brachymetaphalangia and mental retardation, similar to that observed in Albright hereditary osteodystrophy (AHO). Four patients had cytogenetically visible de novo deletions of chromosome 2q37. The fifth patient was cytogenetically normal and had normal bioactivity of the α subunit of Gs (Gsα), the protein that is defective in AHO. In this patient, we have used a combination of highly polymorphic molecular markers and FISH to demonstrate a microdeletion at 2q37. The common region of deletion overlap involves the most telomeric 2q marker, D2S125, and extends proximally for a maximum distance of 17.6 cM. We suggest this represents a consistent phenotype associated with some deletions at 2q37 and that genes important for skeletal and neurodevelopment lie within this region. Screening for deletions at this locus should be considered in individuals with brachymetaphalangia and mental retardation. Furthermore, 2q37 represents a candidate region for type E brachydactyly.

Classification and identification of inherited brachydactylies

Abstract: A search for patterns of malformation in the brachydactylies has resulted in new ways to identify the different types. Type A-1 can be characterised by a proportionate reduction of the middle phalanges. Type B is thought to be an amputation-like defect. In type C the fourth middle phalanx is usually the longest, and type E (Riccardi and Holmes, 1974) is characterised by short metacarpals and short distal phalanges. Short stature is usually present in type A-1 and type E brachydactyly (Riccardi and Holmes, 1974) and it may be present in some individuals with brachydactyly C. As short children have short hands, it is possible that in patients with very mild expressions of brachydactyly the cause of the short stature may be overlooked. It is suggested that in every child with proportionate short stature the hands should be carefully examined. If the hands are disproportionately short, if any distal creases are missing, if there is a shortening, however mild, of any finger, if any metacarpals are short, then it is important to have ϰ-rays to look for brachydactyly A-1, C, or E. Much information is still needed. It is important in future reports to have skeletal surveys, pattern profile analyses, and to note the height of children with brachydactyly C. Most interesting of all will be when fetal limbs of each type become available for study.

Dose dependent expression of HDAC4 causes variable expressivity in a novel inherited case of brachydactyly mental retardation syndrome.

Abstract: Histone deacetylase 4 (HDAC4) serves important roles in multiple human systems, including neurological, cardiac, and skeletal functions. Mutation or deletion of HDAC4 causes brachydactyly mental retardation syndrome (BDMR), a disorder that includes intellectual disability, behavioral abnormalities, autism spectrum disorder, and craniofacial and skeletal anomalies, including brachydactyly type E. We present a case of familial BDMR, including a parent with mild symptoms of the disorder and a child exhibiting a more severe phenotype. Cytogenetic testing showed a cryptic balanced translocation in the mother that resulted in a 2q37.1 monosomy and a 10q26.1 trisomy in the son. Gene expression analyses demonstrated 67% HDAC4 expression in the mother and 23% HDAC4 expression in the son relative to normal controls, lending evidence to the hypothesis that HDAC4 modulates severity of this disorder in a dosage-dependent manner.

Monogenic hypertension: Lessons from the genome

Abstract: of her family members. Her daughter’s development apparently was normal. The patient could give no information regarding the daughter’s blood pressure, or even whether the blood pressure had ever been taken. The patient was 157 cm tall and weighed 47 kg. Her blood pressure was 280/160 mm Hg; heart rate, 80 beats/min; respiratory rate, 16/min. The physical examination, with the exception of short stature and brachydactyly, was unremarkable. Fundoscopic examination disclosed no hemorrhages or exudates, the heart was not palpably enlarged, she had no cardiac murmurs, and no bruits could be heard over any vessels. Her blood count, urinalysis, and serum chemistries, including electrolytes, were normal. The creatinine clearance was 76 mL/ min with a sodium, potassium, and calcium excretion of 122, 38, and 1.3 mmol/day, respectively. Plasma renin activity (PRA) and plasma aldosterone (supine posture) were 14 ng/mL/h and CASE PRESENTATION 666 pg/mL, respectively; the urinary aldosterone excretion was A 50-year-old female schoolteacher was referred to us for 16.7 g/day. Bilateral adrenal vein aldosterone sampling rethe evaluation of arterial hypertension. At that time, she was vealed no lateralization. Plasma and urinary norepinephrine taking no antihypertensive medications. The condition was diagvalues were normal. The renal and adrenal ultrasound examinosed when the patient was 15 years old, but no treatment was nation was normal. An echocardiogram disclosed moderate initiated then. At age 31, her blood pressure increased precipiconcentric left-ventricular hypertrophy without diastolic dystously during her only pregnancy, which nevertheless culmifunction and with a preserved ejection fraction. A 24-hour ambunated in the otherwise uncomplicated delivery of a daughter. latory blood pressure measurement confirmed severe hypertenSubsequently, a variety of medications were tried with only sion; however, the nocturnal blood pressure decrease was modest control of blood pressure. In 1993, an extensive evaluapreserved. The patient refused magnetic resonance imaging of tion was performed at another hospital, including renal angiogthe posterior fossa vessels because of claustrophobia. Her blood raphy. The patient underwent bilateral percutaneous dilation pressure was successfully reduced with hydrochlorothiazide, of her renal arteries, but her blood pressure did not decrease. triamterene, amlodipine, enalapril, and carvedilol. She was reHer only complaints were occasional nausea, headache, and ferred to the Franz Volhard Clinic for autonomic testing, but lightheadedness. She denied history of stroke, visual loss, shortshe failed to appear. ness of breath, or knowledge of cardiovascular sequelae. Her past medical history was unremarkable, with the exception of brachydactyly. A geneticist at another university had DISCUSSION seen her when she was 27 years old, and type E brachydactyly Dr. Friedrich C. Luft (Head, Division of Nephrology was diagnosed (Fig. 1). No connection between the brachydactyly and hypertension was made at that time. and Hypertension, Franz Volhard Clinic, Berlin, Germany): The patient was born in Silesia (Poland). Her mother also This patient has severe hypertension and type E brachyhad brachydactyly, as did other members of the family. Her dactyly, a genetic condition. The physicians engaged in brother, the sole sibling, did not have brachydactyly. Since her care considered the possibility that she has autosomoving to Germany, she has had no further contact with any mal-dominant hypertension and brachydactyly as described by Bilginturan in 1973 in a family from Turkey [1]. Consistent with this diagnosis is the fact that she has The Nephrology Forum is funded in part by grants from Amgen, Incorporated; Merck & Co., Incorporated; and Dialysis Clinic, Incorpotype E brachydactyly, plasma renin activity and plasma rated. aldosterone values in the high-normal range, normal circulating catecholamines, and no other causes for second

Short stature, type E brachydactyly, exostoses, gynecomastia, and cryptorchidism in a patient with 47,XYY/45,X/46,XY mosaicism.

Abstract: We report a 72-year-old male patient with a 47,XYY/45,X/46,XY mosaicism associated with short stature, exostoses, type E brachydactyly, gynecomastia, cryptorchidism, mild mental retardation, and a paranoid personality and conversion disorder. Since his prevalent cell line was 47,XYY (about 75%), our patient could be karyotypically classified as a case of 47,XYY syndrome. In view of the striking similarity of the clinical features of this case and those of a XYY case previously reported by Ikegawa et al (1992), it seems reasonable to suggest that these patients are representatives of a novel syndrome with a XYY karyotype.