BACKGROUND: Allan-Herndon-Dudley syndrome (AHDS) results from a pathogenic variant in the hemizygous subunit of the SLC16A2 gene, which encodes monocarboxylate transporter 8 and follows an X-linked recessive pattern. AHDS manifests as neuropsychomotor developmental delay, intellectual disability, movement disorders, and thyroid hormone abnormalities. It is frequently misdiagnosed as cerebral palsy or hypothyroidism.
METHODS: A 9-month-old male infant exhibited poor head control, hypodynamia, motor retardation, hypertonic limbs, and thyroid abnormalities. Despite levothyroxine supplementation and rehabilitation therapy, no improvements were observed. Whole-exome sequencing identified a novel nonsense mutation in SLC16A2 (c.124G > T, p.E42X), which unequivocally established the diagnosis.
METHODS: AHDS was confirmed.
METHODS: Levothyroxine treatment commenced early in infancy, followed by 3 months of rehabilitation therapy, starting at 5 months of age. The combined administration of levothyroxine and methimazole was initiated at 1 year and 10 months of age, respectively.
RESULTS: While improvements were noted in thyroid hormone levels, neurological developmental delays persisted.
CONCLUSIONS: AHDS should be considered in patients presenting with atypical neurological features and thyroid hormone abnormalities such as elevated triiodothyronine and decreased thyroxine levels. The early utilization of exome sequencing aids in prompt diagnosis. The identified SLC16A2 nonsense mutation correlates with severe neurological phenotypes and adds to the spectrum of genetic variations associated with AHDS.

BACKGROUND: Deficiencies in the thyroid hormone transporter monocarboxylate 8 (MCT8) due to pathogenic variants in the SLC16A2 gene (OMIM 300095) result in a complex phenotype with main endocrine and neurologic symptoms. This rare disorder, named Allan-Herndon-Dudley syndrome (AHDS) (OMIM 300523), is inherited in an X-linked trait. One of the prominent features of AHDS is the presence of movement disorders (MD), which are complex and carry a significant burden of the disease.
METHODS: Patient 1: male with hypotonia since birth, developmental delay, dystonic posturing at 4 months and at 15 months, and startle reaction developed with sensory stimuli. Patient 2: male, at 2 months, shows hypotonia and developmental delay, paroxysmal episodes triggered by a stimulus with sudden blush, tonic asymmetric posture, and no epileptiform activity. At 10 months, generalized dystonic posturing. Patient 3: typical neurodevelopmental milestones until 6 months; at 24 months, dystonia, startle reaction, and upper motoneuron signs.
CONCLUSIONS: We aim to describe our patients diagnosed with AHDS, focusing on MD phenomenology and strengthening the phenotype-genotype correlations for this rare condition.

暂无摘要。

暂无摘要。

Pathogenic variation of the MECP2 gene presents mostly as Rett syndrome in females and is extremely rare in males. Most male patients with MECP2 gene mutation show MECP2 duplication syndrome.
Here we report a rare case in a 10-month-old boy with a hemizygous insertion mutation in MECP2 as NM_001110792, c.799_c.800insAGGAAGC, which results in a frameshift mutation (p.R267fs*6). The patient presented with severe encephalopathy in the neonatal period, accompanied by severe development backwardness, hypotonia, and ocular and oropharyngeal dyskinesia. This is the first report of this mutation, which highlights the phenotype variability associated with MECP2 variants.
This case helps to expand the clinical spectrum associated with MECP2 variants. Close attention should be paid to the growth and development of patients carrying a MECP2 variant or Xq28 duplication. Early interventions may help improve symptoms to some certain extent.

Börjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked intellectual disability. The main features of the patients include intellectual disability/global developmental delay, characteristic face, anomalies of fingers and toes, hypogonadism, linear skin hyperpigmentation, and tooth abnormalities in female patients, and obesity in male patients. A case of BFLS caused by a novel mutation of PHF6 gene who was treated in the Department of Pediatrics, Xiangya Hospital, Central South University was reported. The 11 months old girl presented the following symptons: Global developmental delay, characteristic face, sparse hair, ocular hypertelorism, flat nasal bridge, hairy anterior to the tragus, thin upper lip, dental anomalies, ankyloglossia, simian line, tapering fingers, camptodactylia, and linear skin hyperpigmentation. The gene results of the second-generation sequencing technology showed that there was a novel heterozygous mutation site c.346C>T (p.Arg116*) of the PHF6 (NM032458.3), variation rating as pathogenic variation. During the follow-up, the patient developed astigmatism, strabismus, awake bruxism, and stereotyped behavior, and the linear skin hyperpigmentation became gradually more evident. The disease is lack of effective therapy so far.
Börjeson-Forssman-Lehmann综合征(Börjeson-Forssman-Lehmann syndrome，BFLS)是一种罕见的X连锁智力障碍性疾病，主要临床表现为智力障碍/全面发育落后、特殊面容、手指和足趾异常、性腺功能减退，女性患者多见线状皮肤色素沉着和牙齿异常，男性患者多见肥胖。中南大学湘雅医院儿科收治1例PHF6基因新发突变致BFLS病例。本例为11个月的女性患儿，临床表现为全面发育落后，特殊面容，头发稀疏，眼距增宽，鼻梁低平，耳屏前多毛，上唇薄，牙齿异常，舌系带过短，通贯掌，锥形指，双手小指弯曲，线样皮肤色素沉着斑。二代测序技术结果显示PHF6基因(NM_032458.3)存在新发c.346C>T(p.Arg116*)杂合突变，变异评级为致病性变异。随访期间患儿出现散光、斜视、清醒磨牙症、刻板行为，皮肤色素沉着颜色较前加深。本病目前尚无特异性治疗方法。.

Mutations in the X-linked methyl-CpG-binding protein 2 (MECP2) gene were first described as a cause of Rett syndrome. MECP2 duplication can cause intellectual disability, developmental delay, severe feeding difficulties, and recurrent infections. Here, we report a Korean family with MECP2 duplication syndrome, which was previously misdiagnosed as cerebral palsy. A man in his early 30 s visited our clinic with intellectual disability, speech impairment, epilepsy, and progressive spasticity. He had been previously misdiagnosed with cerebral palsy, and had received orthopedic surgeries such as musculotendinous lengthening and derotational osteotomy. After the surgeries, he received comprehensive rehabilitation. Upon carefully checking his family history, we noted that his younger brother had similar symptoms. Next-generation sequencing revealed whole exon duplication in MECP2 in both the patient and his brother; their mother also had this genetic mutation but was asymptomatic. Early diagnosis is essential for improving the success of MECP2 duplication syndrome treatment. Individuals with MECP2 duplication syndrome should be referred to specialists to manage multidisciplinary symptoms and to regularly check for complications that are common in this syndrome.

BACKGROUND: Lysine(K)-specific demethylase 5C (KDM5C) dysfunction causes X-linked syndromic intellectual developmental disorder Claes-Jensen type in male patients. The clinical presentations of female individuals with heterozygous KDM5C variations vary widely and are only now beginning to be characterized in detail.
METHODS: Herein, we identified a novel de novo heterozygous nonsense variation of KDM5C (c.3533C > A, p.S1178X) in a sporadic 4-year-old Chinese girl, who presented with Claes-Jensen type-like phenotypes, such as moderate developmental delay, serious expressive language delay, short stature, microcephaly, and typical facial particularities. Moreover, X-chromosome inactivation (XCI) analysis showed no significant skewed X-inactivation.
CONCLUSIONS: The report expands the genotype of KDM5C variation in female patients, delineates the phenotype of affected females in this well-known X-linked disorder, and also reinforces the necessity to consider this X-linked gene, KDM5C, in sporadic female patients.

暂无摘要。

Alpha-thalassemia X-linked intellectual disability syndrome (ATRX) is a rare genetic condition caused by mutations in the ATRX gene characterized by distinctive dysmorphic features, alpha thalassemia, mild-to-profound intellectual disability, and epilepsy, reported in nearly 30% of the patients. To date, different types of seizures are reported in patients with ATRX syndrome including either clonic, tonic, myoclonic seizures or myoclonic absences. However, an accurate analysis of electroencephalographic features is lacking in literature. We report on the epileptic and electroencephalographic phenotype of seven unpublished patients with ATRX syndrome, highlighting the presence of a peculiar EEG pattern characterized by diffuse background slowing with superimposed low voltage fast activity. Likewise, we also review the available literature on this topic.