Identification of a founder effect involving n.197C>T variant in RMRP gene associated to cartilage-hair hypoplasia syndrome in Brazilian patients.

Cartilage-hair hypoplasia syndrome (CHH) is an autosomal recessive disorder frequently linked to n.72A>G (previously known as n.70A>G and n.71A>G), the most common RMRP variant worldwide. More than 130 pathogenic variants in this gene have already been described associated with CHH, and founder alterations were reported in the Finnish and Japanese populations. Our previous study in Brazilian CHH patients showed a high prevalence of n.197C>T variant (former n.195C>T and n.196C>T) when compared to other populations. The aim of this study was to investigate a possible founder effect of the n.197C>T variant in the RMRP gene in a series of CHH Brazilian patients. We have selected four TAG SNPs within chromosome 9 and genotyped the probands and their parents (23 patients previously described and nine novel). A common haplotype to the n.197C>T variant carriers was identified. Patients were also characterized for 46 autosomal Ancestry Informative Markers (AIMs). European ancestry was the most prevalent (58%), followed by African (24%) and Native American (18%). Our results strengthen the hypothesis of a founder effect for the n.197C>T variant in Brazil and indicate that this variant in the RMRP gene originated from a single event on chromosome 9 with a possible European origin.

Extensive and deep granulomatous ulcers as an atypical manifestation of cartilage-hair hypoplasia syndrome: A diagnostic and therapeutic challenge.

Cartilage hypoplasia syndrome is a primary immunodeficiency disease characterized by short stature, hypoplastic hair and a variable degree of immunodeficiency. Noninfectious cutaneous granulomas represent an uncommon yet well-recognized manifestation within the spectrum of primary immunodeficiency diseases. However, cutaneous granulomas as a manifestation of cartilage-hair hypoplasia syndrome, are extremely rare. We present a case of a middle-aged man with cartilage hypoplasia syndrome featuring cutaneous granulomas, manifesting as chronic, extensive and deep cutaneous ulcers. The patient was treated with anti-TNF-alpha adalimumab with partial improvement. Our case underscores the broad spectrum of clinical manifestations associated with cartilage hypoplasia syndrome and adds new evidence to the potential therapeutic efficacy of anti-TNF-alpha drugs in its treatment.

Anesthetic management of scoliosis operation in a pediatric patient with Frank-ter Haar syndrome: a case report.

Frank-ter Haar syndrome is a rare disorder characterized by multiple skeletal, cardiovascular abnormalities, and facial features. Some of these characteristic facial features are important for anesthesiologists to predict the difficult airway. We present the anesthesia management of an 8-year-old boy with Frank-ter Haar syndrome who underwent posterior spinal instrumentation operation for scoliosis. In these patients, it is vital to anticipate possible difficult intubation before surgery and make all necessary preparations.

[Cartilage-hair hypoplasia. A case report]. / Hipoplasia cartílago-cabello. Reporte de un caso.

BACKGROUND: Cartilage-hair hypoplasia is a rare autosomal recessive disease, which is characterized by metaphyseal chondrodysplasia and thin hair. It can be accompanied by immunological disorders in varying degrees. CLINICAL CASE: The case of a 35-month-old girl is described. Since her birth, with growth restriction, she has developed pneumonia eleven times, malabsorption syndrome and aganglionic megacolon, which is why she was diagnosed with cartilage-hair hypoplasia, with expression of non-severe combined immunodeficiency. The decision was to proceed with hematopoietic stem cell transplantation. At the time of this report, the patient was free from infectious processes. CONCLUSION: Cartilage-hair hypoplasia is a condition with diverse clinical features and different degrees of immunodeficiency. As part of the treatment, it is possible to perform haematopoietic stem cell transplantation.

Antecedentes: La hipoplasia cartílago-cabello es una enfermedad autosómica recesiva poco frecuente, caracterizada por condrodisplasia metafisaria y cabello fino. Puede estar acompañada de alteraciones inmunológicas en distintos grados. Caso clínico: Niña de 35 meses de edad, quien desde su nacimiento mostró restricción del crecimiento; desarrolló 11 cuadros de neumonía, síndrome de malabsorción y megacolon agangliónico, por lo que se diagnosticó hipoplasia cartílago-cabello, con expresión de inmunodeficiencia combinada no severa. Se decidió trasplante de células madre hematopoyéticas. Al momento de este informe, la paciente estaba libre de procesos infecciosos. Conclusión: La hipoplasia cartílago-cabello es un padecimiento con rasgos clínicos y distintos grados de inmunodeficiencia. Como parte del tratamiento es posible realizar trasplante de células madre hematopoyéticas.

Clinical and molecular diagnosis of a cartilage-hair hypoplasia with IGF-1 deficiency.

Cartilage-hair hypoplasia syndrome (CHH) is a rare autosomal recessive condition characterized by metaphyseal chondrodysplasia and characteristic hair, together with a myriad of other symptoms, being most common immunodeficiency and gastrointestinal complications. A 15-year-old Mexican male initially diagnosed with Hirschsprung disease and posterior immunodeficiency, presents to our department for genetic and complementary evaluation for suspected CHH. Physical, biochemical, and genetic studies confirmed CHH together with IGF-1 deficiency. For this reason, we propose IGF-1 replacement therapy for its well-known actions on hematopoiesis, immune function and maturation, and metabolism. © 2016 Wiley Periodicals, Inc.

Whole-exome sequencing reveals a novel COL2A1 mutation in a patient with spondylo-epiphyseal dysplasia congenita.

Skeletal dysplasia is a group of disorders with more than 450 entities, many of which cannot be differentiated, especially during infancy, but could lead to different clinical courses and prognoses. In this study, we have described a case of a Thai infant with short stature, flat face, pectus carinatum, indirect inguinal hernia, platyspondyly, and generalized delayed endochondral ossification. Using whole-exome sequencing (WES), we successfully identified a de novo heterozygous mutation, c.2024G>A (p.G675D), in the COL2A1 gene, which, to our knowledge, has not been previously reported. These molecular findings helped provide a definite diagnosis of spondyloepiphyseal dysplasia congenita, aiding in proper management of the disease and improved genetic counseling. We demonstrated that WES is an efficient and cost-effective tool for molecular diagnosis for a type II collagenopathy.

Hypoplastic anemia in cartilage-hair hypoplasia-balancing between iron overload and chelation.

OBJECTIVE: To evaluate the severity of iron overload and the success of iron chelation therapy in patients with cartilage-hair hypoplasia (CHH) and hypoplastic anemia, with particular focus on adverse effects of iron chelators. STUDY DESIGN: Four of the 23 presently surviving Finnish patients with CHH under 18 years of age are dependent on regular red blood cell transfusions. Their hospital records were reviewed for history of anemia and chelation therapy. Cumulative iron load from transfusions was calculated. Efficacy of the chelation therapy was evaluated biochemically and by liver iron content assessments. RESULTS: At the introduction of iron chelation, the patients had received on average 99 (37-151) transfusions; the mean cumulative iron overload was 4640 (800-8200) mg, the annual iron accumulation rate 0.35 (0.25-0.41) mg/kg/d, and the mean plasma ferritin was 2896 (1217-6240) µg/L. Liver iron content, determined by biopsy in 3 patients, was on average 20.0 (6.6-30.0) mg/g liver dry weight. All patients, except 1 with Hirschsprung disease, tolerated deferoxamine, deferiprone, and deferasirox therapy well, showing only mild adverse effects typical for the agents. Plasma ferritin levels and liver magnetic resonance imaging T2* of iron overload showed successful chelation. CONCLUSION: Iron chelation is well tolerated in patients with CHH, with possible exception of patients with Hirschsprung disease. Successful chelation will prepare for hematopoietic stem cell transplantation in patients with CHH with persistent transfusion dependency.

Congenital hypertrichosis, osteochondrodysplasia, and cardiomegaly: further delineation of a new genetic syndrome.

The hypertrichosis and osteochondrodysplasia syndrome is a rare entity with clinical findings including macrosomia at birth cardiomegaly. Autosomal recessive inheritance is presumed based on the report of two affected sibs born to healthy parents. Here we report on four new patients with their follow-up data, as well as on one of the four cases from the original report. Comparison of all eight cases indicates that they share 50% of clinical and radiological changes. This report contributes to the further delineation of this newly recognized syndrome.