Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal, and calcaneal fusions, and behavioral differences. ...Reduced penetrance and variable expressivity contribute to the wide spectrum of clinical findings. Muenke syndrome constitutes the most common syndromic form of craniosynostosis, with an incidence of 1 in 30,000 births and is defined by the presence of the p.Pro250Arg mutation in FGFR3. Participants were recruited from international craniofacial surgery and genetic clinics. Affected individuals, parents, and their siblings, if available, were enrolled in the study if they had a p.Pro250Arg mutation in FGFR3. One hundred and six patients from 71 families participated in this study. In 51 informative probands, 33 cases (64.7%) were inherited. Eighty-five percent of the participants had craniosynostosis (16 of 103 did not have craniosynostosis), with 47.5% having bilateral and 28.2% with unilateral synostosis. Females and males were similarly affected with bicoronal craniosynostosis, 50% versus 44.4% (P = 0.84), respectively. Clefting was rare (1.1%). Hearing loss was identified in 70.8%, developmental delay in 66.3%, intellectual disability in 35.6%, attention deficit/hyperactivity disorder in 23.7%, and seizures in 20.2%. In patients with complete skeletal surveys (upper and lower extremity x-rays), 75% of individuals were found to have at least a single abnormal radiographical finding in addition to skull findings. This is the largest study of the natural history of Muenke syndrome, adding valuable clinical information to the care of these individuals including behavioral and cognitive impairment data, vision changes, and hearing loss.
Objective To investigate executive function and adaptive behavior in individuals with Muenke syndrome using validated instruments with a normative population and unaffected siblings as controls. ...Study design Participants in this cross-sectional study included individuals with Muenke syndrome (P250R mutation in FGFR3 ) and their mutation-negative siblings. Participants completed validated assessments of executive functioning (Behavior Rating Inventory of Executive Function BRIEF) and adaptive behavior skills (Adaptive Behavior Assessment System, Second Edition ABAS-II). Results Forty-four with a positive FGFR3 mutation, median age 9 years, range 7 months to 52 years were enrolled. In addition, 10 unaffected siblings served as controls (5 males, 5 females; median age, 13 years; range, 3-18 years). For the General Executive Composite scale of the BRIEF, 32.1% of the cohort had scores greater than +1.5 SD, signifying potential clinical significance. For the General Adaptive Composite of the ABAS-II, 28.2% of affected individuals scored in the 3rd-8th percentile of the normative population, and 56.4% were below the average category (<25th percentile). Multiple regression analysis did not identify craniosynostosis as a predictor of BRIEF ( P = .70) or ABAS-II scores ( P = .70). In the sibling pair analysis, affected siblings performed significantly poorer on the BRIEF General Executive Composite and the ABAS-II General Adaptive Composite. Conclusion Individuals with Muenke syndrome are at an increased risk for developing adaptive and executive function behavioral changes compared with a normative population and unaffected siblings.
The clinical features specific to tethered cord syndrome (TCS) in adults as well as factors determining outcome and prognosis have rarely been addressed systematically. The authors studied 56 ...patients, 54 of whom were treated surgically over the last 16 years.
In 17 patients who had been asymptomatic during childhood, TCS was diagnosed 8 years after onset of symptoms. Tethered cord syndrome was diagnosed 4 years after worsening in 39 patients with neurological signs or symptoms since childhood. The patients were followed for an average of 8 years. Features specific to adult-age presentation included nondermatomal pain aggravated by movement in 34 patients and conditions such as pregnancy and childbirth (in five of 11 pregnant patients). The most frequent tethering lesions were lipoma in 32, tight terminal filum in 28, and split cord malformation and secondary adhesions in 12 patients, respectively. Improvement or stabilization of symptoms at 6 months after surgery was noted in 46 (85%) of 54 patients. Improvement in pain status was most frequent (86%) followed by improvements in spasticity (71%), bladder dysfunction (44%), and sensorimotor deficits (35%). Factors associated with adverse outcome included preoperative duration of neurological deficits more than 5 years and incomplete untethering. On average, 8 (80%) of 10 patients with incomplete untethering developed recurrent symptoms 5 years after surgery compared with only seven (16%) of 44 patients in whom complete untethering was achieved. Seven patients underwent reoperation and in five of them stabilization of symptoms was attained. At a mean follow up of 8 years, 46 (85%) of the 54 surgically treated patients were in stable neurological condition, including those in whom reoperation was performed.
Surgery for TCS is as beneficial in adults as it is in children. Its success depends on early diagnosis and complete untethering of the spinal cord.
We have characterized a novel autosomal recessive Crouzon‐like craniosynostosis syndrome in a 12‐affected member family from Antakya, Turkey, the presenting features of which include: multiple suture ...synostosis, midface hypoplasia, variable degree of exophthalmos, relative prognathism, a beaked nose, and conductive hearing loss. Homozygosity mapping followed by targeted next‐generation sequencing identified a c.479+6T>G mutation in the interleukin 11 receptor alpha gene (IL11RA) on chromosome 9p21. This donor splice‐site mutation leads to a high percentage of aberrant IL11RA mRNA transcripts in an affected individual and altered mRNA splicing determined by in vitro exon trapping. An extended IL11RA mutation screen was performed in a cohort of 79 patients with an initial clinical diagnosis of Crouzon syndrome, pansynostosis, or unclassified syndromic craniosynostosis. We identified mutations segregating with the disease in five families: a German patient of Turkish origin and a Turkish family with three affected sibs all of whom were homozygous for the previously identified IL11RA c.479+6T>G mutation; a family with pansynostosis with compound heterozygous missense mutations, p.Pro200Thr and p.Arg237Pro; and two further Turkish families with Crouzon‐like syndrome carrying the homozygous nonsense mutations p.Tyr232* and p.Arg292*. Using transient coexpression in HEK293T and COS7 cells, we demonstrated dramatically reduced IL11‐mediated STAT3 phosphorylation for all mutations. Immunofluorescence analysis of mouse Il11ra demonstrated specific protein expression in cranial mesenchyme which was localized around the coronal suture tips and in the lambdoidal suture. In situ hybridization analysis of adult zebrafish also detected zfil11ra expression in the coronal suture between the overlapping frontal and parietal plates. This study demonstrates that mutations in the IL11RA gene cause an autosomal recessive Crouzon‐like craniosynostosis.
Our results provide evidence for a crucial and conserved role of IL11RA during craniofacial development and suture formation. Impaired IL11RA function causes autosomal recessively inherited syndromic craniosynostosis. We propose an inhibitory effect of Il11ra within sutures, thereby preventing their premature fusion.
Friedrich Weickmann (1913-1983): some reminiscences Nisch, Gunther; Collmann, Hartmut
Journal of neurological surgery. Part A, Central European neurosurgery,
01/2015, Letnik:
76, Številka:
1
Journal Article
Recenzirano
Friedrich Weickmann was one of the most distinguished neurosurgeons of the former German Democratic Republic and an eminent representative of the neurosurgical school established by Fedor Krause. For ...25 years he was head of the neurosurgical department in Berlin-Buch, which he developed into an excellent nonuniversity center. Weickmann was the first German to publish a comprehensive text on pediatric neurosurgery. He deserves particular credit for defending the autonomy of the neurosurgical specialty and for promoting neuroradiology as a subspecialty of radiology.
We defined parameters that could differentiate between positional and synostotic plagiocephaly and defined a diagnostic chart for decision making.
Prospective study.
We examined 411 children with ...non-syndromic skull abnormalities between January 2011 and December 2012.
A total of 8 infants under 1 year of age with proven unilateral non-syndromic lambdoid synostosis (LS) and 261 children with positional deformity were examined to outline the specific clinical features of both diagnoses. After clinical examination, an ultrasound revealed either a closed suture suggestive of LS or a patent lambdoid suture suggestive of positional deformity. For patients with synostosis, plain radiographs, MR imaging and follow-up examinations were performed. In cases of open sutures, only follow-ups were completed.
Clinical, imaging, genesis and treatment differences between positional plagiocephaly and LS.
In all 8 cases of unilateral LS and 258 cases of positional plagiocephaly, the diagnosis was established by clinical examination alone. In three cases of positional plagiocephaly, diagnosis was determined after an additional ultrasonography. MR imaging revealed a unilateral tonsillar herniation in five of the eight children with LS and hydrocephalus in one child.
We have suggested a list of clinical features that specify the underlying cause of posterior plagiocephaly. An additional ultrasound scanning confirmed the diagnosis without any risks of ionising radiation or sedation as in a CT scan.
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