Low Posterior Hairline Research Articles

Sprengel Deformity with Bilateral Huge Omovertebra

Sprengel’s deformity is characterized by the congenital migration of the scapula superiorly in relation to the thoracic cage. Other congenital anomalies, such as Klippel-Feil syndrome, may occur in combination with Sprengel’s deformity. We report on a case of Sprengel’s deformity with a huge bilateral omovertebrae, which was combined with the clinical features of Klippel-Feil syndrome, including cervical fusion, short neck, low posterior hairline, and limitation of neck motion. However, no other deformities or functional defects were observed.

Mutations in MEOX1, Encoding Mesenchyme Homeobox 1, Cause Klippel-Feil Anomaly

Klippel-Feil syndrome (KFS) is a segmentation malformation of the cervical spine; clinically, it manifests as a short neck with reduced mobility and a low posterior hairline. Several genes have been proposed as candidates for KFS when it is present with other associated anomalies, but the genetics of isolated KFS have been difficult to study because of the syndrome's mostly sporadic occurrence. We describe a multiplex consanguineous family in which isolated KFS maps to a single 17q21.31 locus that harbors a homozygous frameshift deletion in MEOX1; this deletion results in complete instability of the transcript. Direct sequencing of this gene in two siblings from another consanguineous family affected by isolated KFS uncovered another homozygous truncating (nonsense) MEOX1 mutation that also leads to complete degradation of the transcript. This gene encodes a transcription factor with a well-established and nonredundant role in somite development, and homozygous null alleles of Meox1 in mice have a cervical skeletal defect that is remarkably similar to the one we observe in human individuals with MEOX1 mutations. Our data strongly suggest that KFS is the human phenotypic equivalent of the sclerotome polarity defect that results from Meox1 deficiency in mice.

Two case reports of an unusual association between Klippel-Feil syndrome and amyotrophic lateral sclerosis: Do they share same genetic defect?

Klippel-Feil syndrome (KFS) is an unusual skeletal disorder characterized by congenital fusion of two or more cervical vertebrae which can be sporadic or familial. KFS emerges to be a failure of the normal segmentation and fusion of the mesodermal somites during 3rd and 8th weeks of embryonic development. The triad of low posterior hairline, short neck, and restricted neck motion is present only in 50% and often associated with scoliosis, spina bifida, Sprengel's deformity, cervical ribs, deafness, cleft palate, renal anomalies, congenital heart defects, and so on because of heterogeneous nature of the disease. The significance of KFS lies in the secondary effects produced on the nervous system, which usually presents with features of progressive cord and brain stem compression with relatively minor trauma. We here report two cases of KFS presented in association with amyotrophic lateral sclerosis. Only two such cases have been described in the literature in 1954 and 1975.

Cervical Klippel-Feil syndrome progressing to myelopathy following minor trauma

Klippel-Feil syndrome (KFS) is a rare disease with a clinical triad of low posterior hairline, short neck, and limited neck motion. Frequent fusion of two or more cervical vertebrae resulting from a congenital segmentation defect can lead to adjacent level hypermobility, instability, and even neurologic symptoms that require surgical intervention. However, surgical results in adults with KFS with concomitant atlantoaxial subluxation and cervical spinal stenosis have not been reported. We report a 58-year-old man with complaints of an unsteady gait, general weakness, and clumsiness in both hands for 6 months. Deep tendon reflexes in both knee joints were increased, with a positive Babinski sign. Bladder and sphincter function were intact. Radiographic findings included C2–C7 congenital fusion with atlantoaxial subluxation and spinal cord compression. He was treated with posterior occipitocervicothoracic fusion, instrumentation, and posterior decompression with a partial craniectomy under the diagnosis of cervical myelopathy. Postoperatively, the neurologic deficits improved without any complications, although bilateral rod breakage was noted at consecutive outpatient department (OPD) follow-ups. He recovered well with residual left hand numbness.

A systematic analysis of small supernumerary marker chromosomes using array CGH exposes unexpected complexity

A small supernumerary marker chromosome is often seen in patients with developmental disorders. Prior to array-based comparative genomic hybridization markers were rarely genotyped end to end. In this study, a valid genotype-to-phenotype correlation was possible because the supernumerary marker chromosomes were fully characterized by array-based comparative genomic hybridization in a genome-wide analysis. Ten consecutive de novo small supernumerary marker chromosome cases were systematically genotyped using G-banding, C-banding, AgNOR staining, whole-genome array-based comparative genomic hybridization, and fluorescence in situ hybridization. Among 10 small supernumerary marker chromosome cases studied, 4 (40%) were not identified by array-based comparative genomic hybridization because of low-level mosaicism or because they lacked euchromatin. One case (10%) was a simple pericentromeric marker extending from 5p13.3 to 5q11.2. Five (50%) markers showed unexpected complexity. Two cases had markers that were derivative acrocentric (AgNOR+) chromosomes with the euchromatin from chromosomes 18p or 19p. Each of the other three cases with complex markers had unusual characteristics including a marker from noncontiguous segments of chromosome 19q, a highly complex rearrangement involving a chromosome 20 homolog as well as the small supernumerary marker chromosome, and a mosaic duplication of a proximal 8p marker. Small supernumerary marker chromosomes are frequently complex on the basis of our small sample. Whole-genome array-based comparative genomic hybridization characterization of the small supernumerary marker chromosome provided informed genetic counseling.

Microduplication of 3p25.2 encompassing RAF1 associated with congenital heart disease suggestive of Noonan syndrome

Noonan syndrome (NS) is a clinically variable and genetically heterogeneous disorder with congenital heart defects (CHD), short stature, and craniofacial dysmorphisms. Gain-of-function mutations in RAF1 can cause NS and the highly related NS with multiple lentigines (previously known as LEOPARD syndrome). Here we report on a 15-year-old male with NS phenotype: short stature, heart defects, low posterior hairline, facial malformations, malformed left ear with sensorineural hearing loss, widely spaced nipples, and unilateral upper limb anomaly. Using high-resolution SNP array technology, we identified in this patient a 0.25 Mb microduplication at 3p25.2 in which RAF1 is located. Sequence analysis did not identify mutations in genes associated with Holt-Oram syndrome. These findings suggest that duplications of genomic regions encompassing RAF1 could cause NS and are consistent with the notion that rare copy number variations encompassing causative genes may underlie a small percentage of patients with syndromic CHD like NS.

Klippel–Feil syndrome associated with situs inversus: Description of a new case and exclusion of GDF1, GDF3 and GDF6 as causal genes

ObjectiveKlippel–Feil syndrome is characterized by faulty segmentation of two or more cervical vertebrae and, in its most severe form, consists of massive cervical vertebral fusion, short neck, low posterior hairline, and limitation of head movement. Several cases associating Klippel–Feil syndrome with situs inversus totalis have been reported. In the present study, we describe the clinical features of a novel case of Klippel–Feil syndrome associated with situs inversus totalis and searched for mutations in GDF1, GDF3 and GDF6 genes, which were recently implicated in the development of skeletal and visceral anomalies. MethodsA case of Klippel–Feil syndrome associated with situs inversus totalis underwent a full clinical examination including X-ray of cervical spine and thorax, abdominal ultrasound, and computerized tomography scanning of thorax and abdomen. PCR amplification and automated nucleotide sequencing of coding exons and intron–exon junctions of GDF1, GDF3, and GDF6 genes were performed in genomic DNA. ResultsNo molecular alterations were found in GDF1, GDF3 and GDF6 genes in this patient. ConclusionAn additional patient associating Klippel–Feil syndrome and situs inversus totalis is reported. Mutations in GDF1, GDF3, and GDF6 genes were excluded as the cause of this unusual clinical association.

Deletion of 18p Syndrome

The deletion of the short arm of chromosome 18 is considered to be 1 of the most frequently occurring chromosomal aberrations, causing a minimal abnormality visible at birth. It usually becomes more apparent after 3 years. The proband is a 15-year-old male who has had phenotypes manifested mainly by brachycephaly, broad faces, ptosis, downturned corners of the mouth, tooth abnormalities, broad neck with low posterior hairline, tunnel chest, hand abnormalities, mental retardation ranging from mild to severe, and other malformations. In addition, the chromosomal analysis for both parents showed normal karyotypes. Phonotypical features were quite similar throughout other cases and in accordance with the usual phenotype of del (18p) suggested within the same cases and among the del (18p) cases described. The abnormality was clearer with a high resolution chromosomal study, which is the detection of subtle chromosome rearrangement that is only possible if the banding resolution is high enough to permit their visualization.

Type III Klippel–Feil syndrome: case report and review of associated craniofacial anomalies

Klippel-Feil syndrome (KFS) is a complex syndrome of osseous and visceral anomalies that include the classical clinical triad of short neck, limitation of head and neck movements and low posterior hairline. It may also be associated with anomalies of the genitourinary, musculoskeletal, neurologic and cardiac systems. We report a case of type III KFS with associated rib anomalies such as cervical rib, fusion and bifid ribs, scoliosis and fused crossed renal ectopia. The aim of this paper was to summarize all craniofacial anomalies that occur in association with KFS, so that clinicians would be aware of them during diagnosis and treatment planning.

50 Years Ago in T he J ournal of P ediatrics: Turner’s Syndrome in the Male

Steiker DD, Mellman MJ, Bongionvanni AM, Eberlein WR, Leboeuf G. J Pediatr 1961;58:321-9 Although described clinically more than two decades earlier, the recognition that most patients with Turner syndrome (TS) were “chromatin negative” emerged only 7 years before this report. Using the “nuclear sexing” system, the interpretation of the absence of Barr bodies (sex chromatin), based on the 1947 Jost experiments in rabbits, was that individuals with TS were genetic males who had undergone prenatal castration resulting in female genitalia and gonadal dysgenesis. Demonstration of the 45, X karyotype and admonition that such persons be considered female with an abnormal genotype rather than a “chromosomal male” or case of “sex reversal” appeared only 2 years before Steiker et al reported their five cases of apparent TS in males. Thus, it is easy to understand their confusion regarding the relationship between these boys and the classic triad of sexual infantilism, congenital webbed neck, and cubitus valgus that comprised the initial description of girls with TS. Not only is a female phenotype now part of its definition, but the manifestations of TS are believed to be primarily caused by haploinsufficiency of one or more of the multitude of genes on the X chromosome, such as SHOX. A likely candidate for what was presumed male Turner syndrome is Noonan syndrome, which is caused by PTPN11 deletions in ∼50% of cases. Although one or more of the five boys probably had Noonan syndrome, it is unlikely that they all did, given the disparate phenotypes. Distinguishing among children with overlapping features such as short stature, abnormal auricles, high arched palate, low posterior hairline, and short or webbed neck was surely a challenge 50 years ago, and, despite advances in molecular and clinical genetics, sometimes remains one to this day. The authors are to be commended for attempting to reconcile a bewildering set of observations, causing them to go so far as to suggest that the features of TS were unrelated to the emblematic chromosomal pattern. This insinuation might seem preposterous to us today, but we should remember the importance of an open mind and consider every conceivable explanation for our findings until the inexorable process of scientific discovery allows the “truth” to become illuminated.

Multiple pterygium syndrome: mimicking the findings of Turner syndrome

Multiple pterygium syndrome (MPS or Escobar syndrome) is a rare, generally autosomal recessive disorder characterized by multiple congenital joint contractures and multiple skin webs. An 11.5-year-old girl with a working diagnosis of Turner syndrome (TS) was referred for her phenotypic features and growth retardation. Pterygium of the neck, low posterior hairline, widely spaced nipples, cubitus valgus, upslanting palpebral fissures, hypertelorism, micrognathia, low-set ears, downturning corners of the mouth, long philtrum, high-arched palate, digital and intercrural webbings, and aplasia of the labia majora were indicative of MPS (Escobar syndrome). Her mental status was normal. Facial asymmetry was present due to cervical webs. Normal karyotype, gonadal functions, and cardiac and urinary system findings helped in excluding TS. Genetic diseases associated with skin webs were revised in differential diagnosis.

UBE2A deficiency syndrome: Mild to severe intellectual disability accompanied by seizures, absent speech, urogenital, and skin anomalies in male patients

We describe three patients with a comparable deletion encompassing SLC25A43, SLC25A5, CXorf56, UBE2A, NKRF, and two non-coding RNA genes, U1 and LOC100303728. Moderate to severe intellectual disability (ID), psychomotor retardation, severely impaired/absent speech, seizures, and urogenital anomalies were present in all three patients. Facial dysmorphisms include ocular hypertelorism, synophrys, and a depressed nasal bridge. These clinical features overlap with those described in two patients from a family with a similar deletion at Xq24 that also includes UBE2A, and in several patients of Brazilian and Polish families with point mutations in UBE2A. Notably, all five patients with an Xq24 deletion have ventricular septal defects that are not present in patients with a point mutation, which might be attributed to the deletion of SLC25A5. Taken together, the UBE2A deficiency syndrome in male patients with a mutation in or a deletion of UBE2A is characterized by ID, absent speech, seizures, urogenital anomalies, frequently including a small penis, and skin abnormalities, which include generalized hirsutism, low posterior hairline, myxedematous appearance, widely spaced nipples, and hair whorls. Facial dysmorphisms include a wide face, a depressed nasal bridge, a large mouth with downturned corners, thin vermilion, and a short, broad neck.

Bilateral Scaphotrapezium Coalition with Bilateral Scaphoid Nonunion in a Patient with Klippel–Feil Syndrome: A Case Report

The purpose of this case report is to discuss the evaluation and management of scaphoid nonunion in patients with congenital musculoskeletal syndromes. Klippel–Feil syndrome (KFS) is a rare disorder characterized by the presence of congenital synostosis of some or all cervical vertebrae [26] caused by a failure in the normal segmentation of the cervical vertebrae during the third to the eighth week of gestation [25]. The classic clinical triad of KFS consists of a short neck, low posterior hairline, and limited neck range of motion due to cervical synostosis [26]. Abnormalities of the hand have been associated with KFS [2, 4, 8, 15, 25] and are predominantly preaxial [2, 4, 15, 25]. One instance of a postaxial anomaly in a patient with KFS has been reported [2]. A prior identification of capitohamate coalition in a patient with Klippel–Feil syndrome was suggested to be a manifestation of a new clinical syndrome [14]. Additional carpal coalitions have not been reported nor have scaphoid abnormalities secondary to the carpal coalitions been described that are associated with Klippel–Feil syndrome.

Partial posterior split cervical spinal cord with Klippel-Feil syndrome

A 50 year-old woman was known with Klippel-Feil syndrome (KFS), consisting of a clinical triad of a short neck, low posterior hairline and restricted neck motion. She was complaining of new onset neck pain radiating down to midscapular region. Physical examination revealed moderate weakness of both biceps and polex muscles. She had diminished sensation of pinprick and light touch between C3-6 dermatoms. Radiographs revealed multiple contiguous fusion between C1 to C6 vertebrae (Fig. A). No sign of instability was detected. Magnetic resonance imaging (MRI) confirmed bony fusion of the vertebral bodies. There is complete fusion between first cervical vertebra to the fourth cervical vertebra and incomplete fusion between fifth and sixth servical vertabrae. The seventh cervical vertebra is normal (Fig. B). Additionally posterior partial split cervical spinal cord from foramen magnum to third cervical vertebra was evident (Fig. C).

Case Report Identification of a de novo inv dup(X)(pter→ q22) by multicolor banding in a girl with Turner syndrome

We report on a 23-year-old girl with short stature, short and wide neck, low posterior hairline, hypogonadism, underdeveloped breasts, infantile uterus, ovaries not visualized, and primary amenorrhea. Cytogenetic G-banding analysis revealed a mosaic karyotype of 46,X,dup(X)(q22)[35]/45,X[15], confirming the clinical suspicion of Turner syndrome. Molecular cytogenetics using a multicolor banding probe set for the X-chromosome characterized an inverted dup(X). The karyotype of the patient was therefore interpreted as 46,X,inv dup(X) (pter --> q22::q22 --> pter). This patient had a mosaic Turner syndrome with a cell line comprising partial trisomy Xpter to Xq22 and partial monosomy Xq22 to Xqter.

Dental team management for a patient with Klippel–Feil syndrome: Case report

Klippel-Feil syndrome (KFS) is a rare congenital abnormality characterized by a short neck, a low posterior hairline, and limited head movement. Occasionally, patients with KFS may also show signs of deafness, intellectual disability, cardiac malformation, palpebral ptosis, facial nerve paralysis, cleft palate, and scoliosis. Although some researchers have documented this syndrome, scant attention has been paid to craniomaxillofacial manifestations and dental treatment of patients with KFS. The objective of this case report was to describe the planning and execution of dental treatment for a 10-year-old male patient with KFS.

Otolaryngologic markers for the early diagnosis of Turner syndrome

Objective To identify and characterize otolaryngologic markers for the early diagnosis of Turner syndrome (TS). Study design Prospective cohort survey. Methods Setting: Clinical Center of the National Institutes of Health (NIH). Patients: Ninety-one females, 7–61 years old (average = 28.7 y), enrolled in a multidisciplinary study of karyotype–phenotype correlations in TS. Main outcome measures: Age at diagnosis, X chromosome karyotype, history of chronic or recurrent otitis media (OM), sensorineural hearing loss (SNHL), palate dysmorphism, pinna deformity, pterygium colli, low posterior hairline, low-set ears, and micrognathia. Results Sixty-nine (76%) patients had a history of chronic or recurrent OM, 62 (68%) had a dysmorphic palate, 57 (63%) had SNHL, and 90 (99%) had one or more of these findings. 83 (91%; average age at diagnosis = 9.4 y) had one or more external craniofacial signs: pinna abnormalities, pterygium colli, low-set ears, micrognathia or a low posterior hairline. Eight patients (average age at diagnosis = 13.2 y) had no external craniofacial signs, although seven (88%) of these eight patients had a history of chronic or recurrent OM, dysmorphic palate or SNHL. The age at diagnosis was not significantly different between groups with or without external craniofacial signs ( P = 0.126). Conclusions Patients with mild or incompletely penetrant TS phenotypes often present with otitis media, hearing loss, or both before the diagnosis of TS is established. Palatal dysmorphism, including ogival morphology, is another otolaryngologic marker for TS. Prompt recognition of these manifestations of TS could hasten its diagnosis and appropriate medical care.

47,XXX/45,X/46,XX mosaicism in a patient with Turner phenotype and spontaneous puberal development

To describe a patient with infertility and phenotypic combination of Turner and triple-X syndrome related to mos 47,XXX/45X/46,XX karyotype. Case report. División de Genética, Centro de Investigación Biomédica de Occidente and Hospital de Ginecología y Obstetricia, CMNO, Instituto Mexicano del Seguro Social. The 24-year-old patient presented a phenotypic combination of Turner syndrome and X polysomy. She showed wide and short neck, low posterior hairline, cubitus valgus, bilateral shortening of the fourth and fifth metacarpals, multiple nevi, and müllerian anomalies but had spontaneous pubarche, thelarche, and menarche. Laboratory evaluations, imaging studies, ovarian biopsy, G-banding karyotype, and in situ fluorescence hybridization. Clinical and laboratory findings. A karyotype: mos 47,XXX/45X/46,XX was found in the cytogenetic studies, a bicornuate uterus in the ultrasonographic scan, and a normal ovarian profile in the laboratory tests. The infertility in the present case can be related to either bicornuate uterus or subclinical abortions due to aneuploid ova. Cytogenetic assessment provides important information regarding infertile patients with uterine factors and short stature.

Dystonia, autoimmune disease and cerebral white matter abnormalities in a patient with 18p deletion

Dystonia is a clinically and genetically heterogeneous disorder of movement characterized by involuntary and sustained muscle contractions and rigid postures affecting one or more sites of the body. It can be classified according to the distribution of affected body parts, age of onset and etiology 1 . Up to now, at least 15 different loci (DYT1–DYT15) have been described in this condition 1,2 . Adult-onset idiopathic torsion dystonia affecting specific parts of the body, such as the eye (blepharospasm), neck (cervical dystonia), and hand (writer’s cramp) has been associated with the DYT7 locus, located in the short arm of chromosome 18 1-3 . Autoimmune diseases have been considered conditions associated with reactions of the immune system against selfantigens or body systems. They are disorders often associated with severe and chronic morbidity. In spite of recent advances, much of their etiology is still unknown 4 . We describe a rare case of a patient with 18p deletion syndrome presenting focal dystonia, Hashimoto thyroiditis, vitiligo and cerebral white matter abnormalities. CaSe The patient is a 30 year old white woman, the fourth child of a non-consanguineous couple, without any history of similar cases in the family. The patient was born full-term, with a Cesarean section, after a pregnancy without intercurrences. During her first year of life, she had several episodes of infection (oti tis and tonsillitis) as well as constipation where laxative use was needed. At 3 months, she had a convulsive crisis during fever. In relation to her neuropsychomotor development, the mother recalls she supported her own head at 6 months and pronounced her first words at the age of three. The patient was also unable to accompany normal school, failing several grades. After a long period without intercurrences, she began with blepharospasm together with cervical dystonia. She presented telarche at the age of 12 and menarche at 13, and at around 20 she began with menstrual irregularity. The hormonal evaluation conducted later diagnosed hypothyroidism due to Hashimoto thyroiditis. During the physical exam at the age of 30, she presented obesity (weighing 70 kg, between the 90–97 percentiles), short stature (149 cm, under the 3 percentile), brachycephaly, but without microcephalia (head circumference of 53 cm – between the 2–50 percentiles), rounded face, ocular hypertelorism (interpupillary distance higher than the 97 percentile), ptosis, blepharospasm, corneal opacification, hypoplasia of the middle third of the face, broad nasal bridge, high palate, short and broad neck, low posterior hairline, broad thorax and accentuated cervical kyphosis (Figs 1A and B). She also had dextroconvex thoracic scoliosis, small hands and feet with hyperconvex nails (Figs 1C and D) and achromic spots of different sizes, spread about the body (thorax, dorsum and members), and vitiligo was diagnosed. The face remained in a fixed position, always turned to the right and downwards (Figs 1A and B). Nuclear magnetic resonance of the skull revealed a dilated ventricular system, with the presence of multiple hypersinal foci at T2 and DP in the semi-oval centers, without gadolinium impregnation, suggestive of demyeliminating lesions, and around the lateral ventricles and third ventricle, suggestive of periependimal leukomalacia (Fig 2A). Electroencephalograph assessment was normal. The thorax radiograph revealed hyperkyphosis with a reduction in body height at the seventh thoracic vertebra and dextroconvex thoracic scoliosis. Ophthalmological evaluation verified the presence of intense photophobia, bilateral keratocone with lower conjunctival pannus in the right eye and the entire left eye. Chromosomal analysis through GTG banding karyotype revealed a deletion involving the short arm of chromosome 18: 46,XX,del(18)(p11.1) (Figs 2B and 2C). The karyotype of the parents was normal.

Anaesthetic management of a patient with Klippel-Feil syndrome

Klippel feil syndrome is a rare entity. After its first description in 1912 by Maurice Klippel, a French neurologist and psychiatrist and Andre Feil, a French neurologist the management of this syndrome still poses a big challenge to clinicians, orthopaedic surgeons , anaesthetists and intensivists. They described patients who have a short neck, decreased range of motion in the cervical spine and a low posterior hairline. It involves congenital failure of segmentation of cervical vertebrae which results from failure of normal segmentation of cervical somites at 3-8 weeks of gestation resulting in multiple fused segments. Spectrum of deformity ranges from fusion of 2 vertebrae to involvement of entire cervical spine. Fusion of C2 & C3 is most common. Here we report the anaesthetic management of a case of Klippel-Feil syndrome who presented with fracture both bones left forearm scheduled for open reduction and internal fixation.