Skeletal syndromes and dysplasias include more than 150 entities, most often of genetic origin. Some of them cause abnormalities in the cervical spine, with or without instability, distortion or compression of the spinal cord. These abnormalities must be detected and treated if necessary because they can have serious consequences such as quadriplegia. Up to 30% of patients with Down syndrome are affected by occipitocervical or atlantoaxial instability. Dynamic cervical spine radiographs are the most common screening tool. Mucopolysaccharidoses (MPS) are a group of inherited lysosomal storage diseases that result in the accumulation of glycosaminoglycans sometimes responsible for craniocervical instability and cervical spinal canal stenosis. Their monitoring requires an MRI every two years. Neurofibromatosis type 1 and syndromes with connective tissue abnormalities (Marfan syndrome, Loeys-Dietz syndrome, Ehlers-Danlos syndrome) can cause severe and unstable cervical spine deformities that may remain asymptomatic for a long time. Cervical X-rays should therefore be performed if there is the slightest doubt. Some rare chondrodysplasias (punctate chondrodysplasia, Larsen syndrome, Metatropic dysplasia) or segmentation anomalies (Klippel Feil syndrome, Sprengel's disease) have cervical spine abnormalities that should be looked for. In case of progression of a deformity (usually kyphosis) or stenosis of the cervical spine, it is important to consider surgical treatment with correction and stabilization. Sometimes preceded by a period of Halo traction, the instrumentation must have "wide" limits and exceed the anatomical limits of the spinal deformity by at least 2-3 levels to prevent the development of an adjacent deformity. The increasing use of surgical navigation techniques allows for greater corrections and more efficient stabilizations, including severe cervical spinal deformities. Vigilance and the detection of these abnormalities remain the key to early and preventive treatment of the complications of these spinal anomalies on often difficult terrain. LEVEL OF EVIDENCE: >V (expert opinion).

Webb-Dattani syndrome (WEDAS) is an extremely rare autosomal recessive disorder caused by pathogenic variants in the ARNT2 gene. It is characterized by a triad of congenital hypopituitarism, structural brain abnormalities, and multisystem developmental defects. We report the case of a 17-year-old girl with WEDAS who presented with global developmental delay, panhypopituitarism, and arginine vasopressin (AVP) deficiency, formerly known as central diabetes insipidus with adipsia, visual impairment, renal anomalies, and spastic quadriplegia. Her endocrine profile revealed deficiencies in ACTH, TSH, and ADH, and gonadotropins, with a possible growth hormone deficiency. Management included hormone replacement with hydrocortisone, levothyroxine, and desmopressin, as well as fluid regulation and supportive care. Despite multiple hospitalizations due to complications including hypernatremia and infections, the patient survived into adolescence - the longest reported survival in this condition to date - before passing away at age 17. This case expands the known clinical phenotype of WEDAS, emphasizing the importance of early recognition, genetic testing, and a multidisciplinary approach to care for affected individuals, particularly in consanguineous populations where the syndrome may be underdiagnosed. Webb-Dattani syndrome (WEDAS) is a rare autosomal recessive disorder caused by an ARNT2 pathogenic variant, presenting with a triad of congenital hypopituitarism, structural brain anomalies, and developmental delay. Adipsic diabetes insipidus is a hallmark complication in WEDAS and requires vigilant fluid management due to the absence of thirst sensation and persistent hypernatremia. Multisystem involvement - including renal anomalies and neurogenic bladder - may occur, expanding the known phenotypic spectrum of ARNT2-related disorders. Early recognition and genetic testing are essential for accurate diagnosis, especially in patients from consanguineous backgrounds presenting with multiple pituitary hormone deficiencies. Long-term survival, although rare, is possible with coordinated multidisciplinary care addressing endocrine, neurological, renal, and infectious complications. This case underscores the importance of individualized endocrine replacement therapy and caregiver education in managing complex syndromic conditions such as WEDAS.

Chiari malformation type 1 (CM1) is a congenital hindbrain malformation characterized by herniation of the cerebellar tonsils below the foramen magnum. The term Chiari type 1.5 is used when herniation of the brainstem under the McRae line and anomalies of the craniovertebral junction are also present. These conditions are associated with several symptoms and signs, including headache, neck pain, and spinal cord syndrome. For symptomatic patients, surgical decompression is recommended. When radiographic indicators of craniovertebral junction (CVJ) instability or symptoms related to ventral brainstem compression are present, CVJ fixation should also be considered. We report the case of a 13-year-old girl who presented with severe tetraparesis after posterior decompression for Chiari malformation type 1.5, followed 5 days later by partial C2 laminectomy. Several months after the initial surgery, she underwent two fixations, first without and then with intraoperative cervical traction, leading to significant neurological improvement. This case report underscores the importance of meticulous radiological analysis before CM surgery. For CM 1.5 patients with basilar invagination, CVJ fixation is recommended, and C2 laminectomy should be avoided. In the event of significant clinical deterioration due to nonadherence to these guidelines, our findings highlight the importance of traction with increased extension before fixation, even years after initial destabilizing surgery.

Congenital cervical stenosis (CCS) is a phenomenon in which an individual has a narrow canal due to abnormal anatomy which can present with earlier degenerative symptoms due to a reduced sagittal diameter. The diagnosis of CCS is important to individual treatment and preventative measures. Often, athletes are warned against sport participation that may cause damage to the cervical spine. There may be a predisposition in certain populations, but lack of data limits conclusions. The current review investigates recent literature on the definition, pathoanatomy, clinical presentation, and management of CCS. It specifically interrogates potential populations predisposed to this condition. The current literature reveals a potential predisposition for CCS in the black population when compared to the white population; however, many studies do not report race when discussing CCS patients. The lack of data limits a consensus on specific populations with a congenitally narrow canal. CCS may be more prevalent in specific populations. With knowledge of populations more at risk for this condition, physicians and teams can be alert when evaluating players and young adults. Furthermore, this may provide insight into risk for symptoms with degenerative disease. These findings introduce an avenue for further research into CCS. Serine deficiency disorders include a spectrum of disease ranging from lethal prenatal-onset Neu-Laxova syndrome to serine deficiency with infantile, juvenile, or adult onset. Neu-Laxova syndrome is characterized by severe intrauterine growth deficiency, microcephaly, congenital bilateral cataracts, characteristic dysmorphic features, limb anomalies, and collodion-like ichthyosis. Infants are typically stillborn or die in early infancy. Infantile-onset serine deficiency is characterized by seizures, microcephaly, developmental delay, intellectual disability, and spastic quadriplegia. Individuals that present with juvenile-onset serine deficiency have seizures and many develop spastic quadriplegia. Adult-onset serine deficiency is characterized by progressive axonal polyneuropathy with ataxia and possible cognitive impairment. The diagnosis of a serine deficiency disorder is established in a proband with biallelic pathogenic variants in PHGDH, PSAT1, or PSPH identified by molecular genetic testing. Targeted therapy: Early treatment with L-serine supplementation; glycine supplementation with L-serine has been used in some individuals. Supportive care: L-serine therapy is more effective than anti-seizure medication for treatment of seizures; developmental and educational support; feeding therapy for persistent feeding issues; treatment of cataracts per ophthalmologist; standard treatments for spasticity and polyneuropathy; preventative dental care for those on oral L-serine powder; social work support and care coordination as needed. Surveillance: Monitor for seizures, changes in tone, contractures, developmental and educational needs, behavior issues, growth and nutrition, constipation and feeding issues, respiratory issues, musculoskeletal manifestations, and family needs at each visit. Dental evaluation every six months. Assessment of care needs when transitioning from pediatric to adult care. Agents/circumstances to avoid: Known triggers of seizure activity (e.g., infection, physical stress, emotional stress). Evaluation of relatives at risk: It is appropriate to evaluate newborn sibs and apparently asymptomatic older and younger sibs of a proband to identify as early as possible those who would benefit from prompt initiation of L-serine treatment. Serine deficiency disorders are inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a serine deficiency-causing pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of inheriting neither of the familial pathogenic variants. Once the serine deficiency-causing pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives and prenatal and preimplantation genetic testing are possible.

Warburg micro syndrome (WARBM) is a rare, autosomal recessive, neurodevelopmental disorder characterized by microcephaly, cortical dysplasia, corpus callosum hypoplasia, congenital hypotonia leading to subsequent spastic quadriplegia, severe developmental delay and hypogenitalism. Ophthalmologic findings that may affect any ocular segment including characteristic, small, atonic pupils. WARBM is known to be caused by biallelic, pathogenic variants in at least five genes although additional genetic loci may exist. The RAB3GAP1 c.748 + 1G>A, p.Asp250CysfsTer24 founder variant has been described in families of Turkish ancestry. We report the clinical and molecular findings in three, unrelated, Turkish families with WARBM. A novel c.974-2A>G variant causing WARBM in three siblings of Turkish descent was found. Functional studies of the novel, c.2606 + 1G>A variant in patients' mRNA revealed skipping of exon 22 which results in a premature stop codon in exon 23. However, the clinical consequences of this variant are blended given that the individual also had a maternally inherited chromosome 3q29 microduplication.