OBJECTIVE: To explore the clinical features and genetic basis of a male patient with Kennedy disease(KD) presenting as secondary infertility. METHODS: A male patient who had presented at Yantai Yuhuangding Hospital in August 2023 for secondary infertility for 5 years was selected as the study subject. Clinical data, laboratory findings, and auxiliary examination of the patient were collected. Peripheral blood samples were obtained from the patient and his family members. Following DNA extraction, whole-exome sequencing (WES) was carried out. Pathogenicity of candidate variant was predicted by bioinformatics analysis. Fluorescence probe PCR-capillary electrophoresis was employed to analyze the trinucleotide CAG repeat sequence variation in the AR gene to rule out dynamic mutation. This study was approved by the Ethics Committee of Yantai Yuhuangding Hospital (Ethics No.: 2024-697). RESULTS: The patient had presented with non-obstructive azoospermia and elevated androgen sensitivity index. Ultrasound scan indicated small testicular volume and seminal vesicle atrophy. WES and bioinformatics analysis revealed abnormal amplification in the patient's AR gene. Fluorescence probe PCR and capillary electrophoresis confirmed that both the proband and his nephew had harbored 52 CAG trinucleotide repeats in exon 1 of the AR gene, confirming the diagnosis of KD. The proband's mother, elder sister, and daughter were identified as carriers of the variant, while his second elder sister did not carry the mutation. CONCLUSION As a rare X-linked recessive genetic disease, KD mainly manifests with muscle weakness, myasthenia gravis and myofascial tremor, while cases with infertility and non-obstructive azoospermia as the initial symptoms are rare and can be easily missed. Diagnosis made by genetic testing needs to be taken seriously by the clinicians.
Humans ; Male ; Bulbo-Spinal Atrophy, X-Linked/diagnosis* ; Adult ; Infertility, Male/genetics* ; Receptors, Androgen/genetics* ; Exome Sequencing ; Mutation ; Pedigree ; Trinucleotide Repeats

Spinal and bulbar muscular atrophy (SBMA) is a rare X-linked motor neuron disease with significant phenotypic viability. Here, we present a genetically identified SBMA family without bulbar paralysis or androgen insensitivity. All four male patients presented with progressive lower motor neuron paralysis in all limbs, with distal extremities more dominant. None of them had bulbar palsy or androgen insensitivity. A consistently mild elevated blood creatine phosphokinase (CPK) levels were detected in all patients and the EMG showed a chronic neurogenic damage. Muscle biopsy of propositus indicated a typical neurogenic amyotrophy. Genetic testing for SMA of mutation in SMN1 was negative, while for SBMA of androgen receptor showed the increased CAG repeat in exon 1, suggesting that although bulbar symptoms and androgen insensitivity are characteristic symptoms of SBMA, they are not obligatory for the diagnosis. In adult males with a chronic motor neuron syndrome without upper motor neuron signs, even in absence of the classical features of androgen insensitivity or bulbar findings, genetic testing for SBMA should be strongly considered.
Adult ; Bulbo-Spinal Atrophy, X-Linked ; complications ; diagnosis ; genetics ; Creatine Kinase ; blood ; Genetic Testing ; Humans ; Male ; Motor Neurons ; pathology ; Muscular Atrophy ; etiology ; Mutation ; genetics ; Paralysis ; diagnosis ; etiology ; Pedigree ; Receptors, Androgen ; genetics

PURPOSE: Spinal and bulbar muscular atrophy (SBMA) is an X-linked motor neuron disease characterized by proximal muscle weakness, muscle atrophy, and fasciculation. Although SBMA is not uncommon in Korea, there is only one study reporting clinical characteristics and genotype-phenotype correlation in Korean patients. MATERIALS AND METHODS: In this study, age at the onset of symptoms, the score of severity assessed by impairment of activities of daily living milestones, and rate of disease progression, and their correlations with the number of CAG repeats in the androgen receptor (AR) gene, as well as possible correlations among clinical characteristics, were analyzed in 40 SBMA patients. RESULTS: The median ages at onset and at diagnosis were 44.5 and 52.5 years, respectively, and median interval between onset and diagnosis and median rate of disease progression were 5.0 years and 0.23 score/year, respectively. The median number of CAG repeats in the AR gene was 44 and the number of CAG repeats showed a significant inverse correlation with the age at onset of symptoms (r=-0.407, p=0.009). In addition, patients with early symptom onset had slower rate of disease progression. CONCLUSION: As a report with the largest and recent Korean cohort, this study demonstrates clinical features of Korean patients with SBMA and reaffirms the inverse correlation between the age at disease onset and the number of CAG repeats. Interestingly, this study shows a possibility that the rate of disease progression may be influenced by the age at onset of symptoms.
Activities of Daily Living ; Adult ; Age of Onset ; Asian Continental Ancestry Group/*genetics ; Bulbo-Spinal Atrophy, X-Linked/genetics/*physiopathology ; Disease Progression ; Female ; Genes, Recessive ; Genetic Association Studies ; Genotype ; Humans ; Male ; Middle Aged ; Muscle Weakness/*physiopathology ; Muscular Atrophy, Spinal ; Muscular Disorders, Atrophic/*genetics ; Phenotype ; Receptors, Androgen/*genetics ; Republic of Korea ; Trinucleotide Repeats/genetics

A 69-year-old man was consulted to our Home Health Care department for home parenteral enteral nutrition. He was diagnosed with Kennedy disease. He had swallowing difficulty and bowel ischemia. We provided nutritional support in a variety of ways in order to suit his condition. The role of the home care nurse involves training methods depending on changes in the nutritional support to patient and care giver. However, in the case of Kennedy disease, increasing the target patient's nutritional requirements as calculated was difficult.
Aged ; Bulbo-Spinal Atrophy, X-Linked* ; Caregivers ; Deglutition ; Delivery of Health Care ; Enteral Nutrition* ; Home Care Services ; Humans ; Ischemia ; Nutritional Requirements ; Nutritional Support ; Parenteral Nutrition

OBJECTIVETo screen for potential mutations of androgen receptor (AR) gene in a patient clinically diagnosed as Kennedy disease.

METHODSPolyglutamine expansion (PQE) induced by a duplication of CAG trinucleotide tandem-repeat in exon 1 of the AR gene was detected with PCR and T-clone sequencing.

RESULTSCompared with the number of CAG repeat of 22 in the normal allele, the number of CAG repeats has increased to 45 in the mutant allele carried by the patient. This has fit with the diagnostic criteria for Kennedy disease.

CONCLUSIONA mutation of PQE has been detected in the patient with Kennedy disease. Detection of PQE in AR gene can be used as reliable method to identify the Kennedy disease.

Base Sequence ; Bulbo-Spinal Atrophy, X-Linked ; blood ; diagnosis ; genetics ; Creatine Kinase ; blood ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Receptors, Androgen ; genetics ; Trinucleotide Repeat Expansion

OBJECTIVETo report on a Chinese family from Wenzhou with genetically confirmed Kennedy disease and describe its clinical and genetic features.

METHODSThe clinical phenotype and the level of relevant biochemical markers were assessed. To determine the number of CAG repeats in the exon 1 of androgen receptor (AR) gene, genomic DNA was extracted from peripheral blood samples of the family members, amplified by PCR and identified by DNA sequencing.

RESULTSThe proband showed predominantly proximal limb weakness, fasciculation, muscle atrophy, gynecomastia, sexual dysfunction and increased serum creatine kinase. Myopathy and neuropathy were identified by electromyography. Two other affected males and 2 affected female carriers were identified to carry an expanded CAG repeat in the AR gene. The numbers of CAG repeats were found to be 43 in the proband, 43 and 42 in the other two affected males, one of which had similar clinical symptoms to the proband.

CONCLUSIONThe family was diagnosed with Kennedy disease by analysis of the AR gene.

Adolescent ; Adult ; Base Sequence ; Bulbo-Spinal Atrophy, X-Linked ; blood ; diagnosis ; genetics ; Creatine Kinase ; blood ; Female ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Pedigree ; Receptors, Androgen ; genetics ; Trinucleotide Repeat Expansion ; Young Adult

OBJECTIVETo study the clinical presentations of Kennedy disease (KD) and compare the neurophysiological features between KD and amyotrophic lateral sclerosis(ALS).

METHODSNine patients with KD, 13 patients with ALS and 26 normal control subjects were recruited. The clinical presentations of KD were analyzed, and the results of nerve conduction studies and electromyography were compared among the 3 groups.

RESULTSThe rates of tongue atrophy and facial fasciculation were 100% and 88.9%, respectively, in the early course and mid-course of KD, sensory damages might be perceived. 2)The sural nerve sensory nerve action potential (SNAP) was not elicited in 56.3% of the patients with KD, and sural nerve SNAP amplitudes were significantly lower in KD (7.9. ± 3.4 µV) than in ALS patients (20.0 ± 5.2 µV) and normal control subjects (26.1 ± 16.8 µV) (P<0.05).

CONCLUSIONB The onset of clinical presentations mimicking motor neuron disease, appearance of tongue atrophy and facial fasciculation in the early and mid-course, and presence of sensory impairment with a decreased sural nerve SNAP amplitude may suggest the diagnosis of KD and should prompt a genetic test for KD.

Amyotrophic Lateral Sclerosis ; physiopathology ; Bulbo-Spinal Atrophy, X-Linked ; physiopathology ; Electromyography ; Evoked Potentials ; Humans

BACKGROUND AND PURPOSE: X-linked bulbospinal muscular atrophy (X-BSMA) is characterized by bulbar and spinal muscular weakness and fasciculations. Although X-BSMA is a motor neuronopathy, there are several reports of myasthenic symptoms or decremental responses to repetitive nerve stimulation (RNS). We report the results of applying the RNS test to 15 patients among 41 with genetically confirmed X-BSMA; these 15 patients complained of fatigue, ease of becoming tired, or early muscular exhaustion. METHODS: The 3-Hz RNS test was performed on the trapezius, nasalis, orbicularis oculi, flexor carpi ulnaris, and abductor digiti quinti muscles. A decrement greater than 10% was considered abnormal. Additionally, a pharmacologic response to neostigmine was identified in three patients. RESULTS: A significant decrement was observed in 67% of patients, and was most common in the trapezius muscle (nine cases). The decrement of the trapezius muscle response ranged from 15.9% to 36.9%. The decrement was inversely correlated with the amplitude of compound muscle action potentials at rest. Neostigmine injection markedly improved the decrement in three patients, who showed noticeable decremental responses to 3-Hz RNS. CONCLUSIONS: This study shows that myasthenic symptoms and abnormal decremental responses to low-rate RNS are common in X-BSMA.
Action Potentials ; Bulbo-Spinal Atrophy, X-Linked ; Fasciculation ; Fatigue ; Humans ; Motor Neuron Disease ; Muscle Weakness ; Muscles ; Muscular Atrophy ; Myasthenia Gravis ; Neostigmine ; Neuromuscular Junction

Acupuncture Therapy ; Adult ; Bulbo-Spinal Atrophy, X-Linked ; therapy ; Humans ; Male

OBJECTIVETo review the clinical and genetic features of a pedigree of Kennedy disease in China.

METHODSThe clinical data of patients from a Kennedy disease family were collected. The numbers of trinucleotide CAG repeats in exon 1 of the androgen receptor gene were determined by DNA sequencing and repeat fragment analysis.

RESULTSIn the pedigree, 4 patients were identified as Kennedy disease. Clinical manifested with adult-onset, progressive proximal limb muscle weakness and atrophy, gynecomastia, oligospermia were also presented. The number of trinucleotide CAG repeats in exon 1 of the androgen receptor gene was 51 in the proband. The electrophysiological study showed sensory and motor involvement and their serum triglycerides values were elevated significantly.

CONCLUSIONAndrogen receptors gene testing is the most reliable diagnosing method, the patients suspected as Kennedy disease should have a gene testing of androgen receptors.

Base Sequence ; Bulbo-Spinal Atrophy, X-Linked ; diagnosis ; genetics ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Pedigree ; Receptors, Androgen ; genetics ; Trinucleotide Repeats ; genetics