Correction to: Bisphosphonate therapy for spinal osteoporosis in Hajdu-Cheney syndrome - new data and literature review.

After publication of this article [1], it is noticed reference no. 17 was incorrectly provided, details are shown below.

Bisphosphonate therapy for spinal osteoporosis in Hajdu-Cheney syndrome - new data and literature review.

BACKGROUND: Hajdu-Cheney syndrome (HCS) (#OMIM 102500) is a rare, autosomal dominant condition that presents in early childhood. It is caused by mutations in the terminal exon of NOTCH2, which encodes the transmembrane NOTCH2 receptor. This pathway is involved in the coupled processes of bone formation and resorption. The skeletal features of HCS include acro-osteolysis of the digits and osteoporosis commonly affecting vertebrae and long bones. Fractures are a prominent feature and are associated with significant morbidity. There is no specific treatment, but with both acro-osteolysis and generalized osteoporosis, it is possible that anti-resorptive treatment might be of benefit. However, to date only a few case reports have evaluated the effectiveness of bisphosphonate treatment. METHODS: We describe the clinical features, treatment regimens and response to bisphosphonate treatment in 7 newly described patients aged 6-39 with HCS, and pooled the data with that from 8 previously published cases (a total of 17 courses of treatment in 15 individuals). RESULTS: The mean lumbar spine bone mineral density (BMD) z-score before treatment was - 2.9 (SD 1.2). In 14 courses of treatment (82%), there was an increase in BMD with bisphosphonate treatment, but the impact (in terms of change in spinal BMD z-score) appeared to be less with advancing age (p = 0.01). There was no evidence that acro-osteolysis was prevented. CONCLUSIONS: Although individual response is variable and age-related, the data support a role for bisphosphonates in preventing or treating spinal osteoporosis in HCS, but bone loss from the lumbar spine may be rapid after cessation.

Mutations in SNORD118 cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts.

Although ribosomes are ubiquitous and essential for life, recent data indicate that monogenic causes of ribosomal dysfunction can confer a remarkable degree of specificity in terms of human disease phenotype. Box C/D small nucleolar RNAs (snoRNAs) are evolutionarily conserved non-protein-coding RNAs involved in ribosome biogenesis. Here we show that biallelic mutations in the gene SNORD118, encoding the box C/D snoRNA U8, cause the cerebral microangiopathy leukoencephalopathy with calcifications and cysts (LCC), presenting at any age from early childhood to late adulthood. These mutations affect U8 expression, processing and protein binding and thus implicate U8 as essential in cerebral vascular homeostasis.

De novo, heterozygous, loss-of-function mutations in SYNGAP1 cause a syndromic form of intellectual disability.

De novo mutations (DNM) in SYNGAP1, encoding Ras/Rap GTPase-activating protein SynGAP, have been reported in individuals with nonsyndromic intellectual disability (ID). We identified 10 previously unreported individuals with SYNGAP1 DNM; seven via the Deciphering Developmental Disorders (DDD) Study, one through clinical analysis for copy number variation and the remaining two (monozygotic twins) via a research multi-gene panel analysis. Seven of the nine heterozygous mutations are likely to result in loss-of-function (3 nonsense; 3 frameshift; 1 whole gene deletion). The remaining two mutations, one of which affected the monozygotic twins, were missense variants. Each individual carrying a DNM in SYNGAP1 had moderate-to-severe ID and 7/10 had epilepsy; typically myoclonic seizures, absences or drop attacks. 8/10 had hypotonia, 5/10 had significant constipation, 7/10 had wide-based/unsteady gait, 3/10 had strabismus, and 2/10 had significant hip dysplasia. A proportion of the affected individuals had a similar, myopathic facial appearance, with broad nasal bridge, relatively long nose and full lower lip vermilion. A distinctive behavioral phenotype was also observed with aggressive/challenging behavior and significant sleep problems being common. 7/10 individuals had MR imaging of the brain each of which was reported as normal. The clinical features of the individuals reported here show significant overlap with those associated with 6p21.3 microdeletions, confirming that haploinsufficiency for SYNGAP1 is responsible for both disorders. © 2015 Wiley Periodicals, Inc.

Warsaw Breakage Syndrome--A further report, emphasising cutaneous findings.

We report a new case of Warsaw Breakage syndrome (WABS) with 2 confirmed mutations in DDX11. Like the previous reported cases [Capo-Chichi et al., 2012; Van der Lelij et al., 2010], there was evidence of pre- and postnatal growth retardation, severe microcephaly, intellectual disability and facial dysmorphism. The patient had sensorineural hearing loss with evidence of bilateral hypoplastic cochleas on imaging, another feature which has been reported in the previous cases of WABS. In our case the patient exhibited a chronic rash of livedo reticularis with telangiectasia on her legs. Abnormally pigmented lesions and cutis mamorata were reported in the original WABS case.

Genitourinary malformations as a feature of the Pallister-Hall syndrome.

Pallister-Hall and McKusick-Kaufman syndromes are developmental disorders with well defined phenotypes, distinct loci and different patterns of inheritance. The clinical features can overlap and may cause diagnostic difficulty, particularly if complex genitourinary malformations are present. A case is presented with features of both syndromes but in which a GLI3 mutation has been identified. A literature review of similar cases is presented and it is proposed that these cases probably represent the Pallister-Hall syndrome. A detailed abdominal and perineal examination should be considered in all female patients with the Pallister-Hall syndrome, looking for associated genitourinary anomalies. Conversely, all girls with features suggestive of McKusick-Kaufman syndrome require neuroimaging to look for features of the Pallister-Hall syndrome. The correct diagnosis is important so that the patient and the family may receive appropriate management. It also allows provision for an accurate recurrence risk.

A family with Duane anomaly and distal limb abnormalities: a further family with the arthrogryposis-ophthalmoplegia syndrome.

A two-generation family is reported in which three members have Duane anomaly and distal limb abnormalities. All three affected have photopic electroretinogram responses that are abnormal or at the lower limit of the normal range with normal scotopic responses. Two affected family members also have hearing loss. The likeliest diagnosis is the syndrome listed as "arthrogryposis-ophthalmoplegia syndrome" on the London Dysmorphology Database or as "arthrogryposis with oculomotor limitation and electroretinal abnormalities" or "oculomelic aplasia" in OMIM [MIM 108145]. In view of the similarities with Okihiro syndrome, a search for mutations within the SALL4 gene was undertaken, but none were identified.

Congenital melanocytic naevus with associated neurofibroma and schwannoma-like change.

Congenital melanocytic naevus and neurofibromatosis type 1 are distinct clinical entities. A diagnosis of neurofibromatosis is difficult to make in the presence of a congenital melanocytic naevus because nodules may arise in the naevus that have similar histopathological appearances to neurofibromata. A case is reported where nodules arising from a naevus were examined histologically and were found to have neurofibroma and schwannoma like elements but strong positivity for S100 protein in keeping with dermal melanocytes. Lisch nodules were also said to be found in the patient but may represent nodular naevi of the irides. It is important that histopathological findings are interpreted within a clinical context and S100 protein immunohistochemical stain is valuable in helping to differentiate these two conditions.

Isochromosome 20p associated with multiple congenital abnormalities.

A second case of tetrasomy 20p due to an additional isochromosome 20p is reported. This resulted in a spontaneous intrauterine death with multiple congenital abnormalities. In keeping with the previous report, the foetus had poor ossification resulting in multiple long bone fractures.