Osteogenesis imperfecta (Ol) type V is distinct Ol phenotype that has recently been described. Patients with this phenotype present characteristically with interosseous membrane calcification and hyperplastic callus formation. We present the clinical and radiographic characteristics of two Filipino families diagnosed to have Ol type V. Through this review of cases, we aim to educate healthcare providers by highlighting salient clinical and radiographic features to aid in the recognition of this specific Ol phenotype, difficulties in diagnosis, current practices in management and fracture prevention, and issues in genetic counseling.

In the Philippines, there is an urgent need to expand the clinical services for diagnosis, management and emotional support for patients with genetic conditions and their family members. Despite the lack of trained providers with specialization in genetics, public health related geneticsprograms are continuously being implemented. These address these current demands,strategic planning began in 2009 between local medical geneticists and international genetic professionals to develop the curriculum for an advanced degree in genetic counseling program. The board of regents at the University of the Philippines approved the proposed curriculum in January 2011, and training of the Philippines first cohort of genetic counseling students commenced in June 2011. The successful implementation of the MS of Genetic Counseling program will provide the opportunity to incorporate the match needed genetic counseling services in the country.
Human ; Male ; Female ; GENETIC COUNSELING ; GENETIC SERVICES ; HEALTH SERVICES

BACKGROUND: Osteogenesis imperfecta is a heritable disorder due to a collagen gene mutation causing a structural abnormality leading to brittle bones and osteopenia. To address the osteopenia, intravenous bisphosphonates (pamidronate) act by temporarily halting the action of osteoclasts giving time for osteoblasts to build bone. To date, there has been no local data regarding the improvement in bone mineral density of filipino patients with osteogenesis imperfecta following treatment.

METHODS: This study is a retrospective review that included six patients aged 1 year and 10months-9 years and 9 months old at the Philippines General Hospital with moderate to severe osteogenesis imperfecta who have undergone six months of pamidronate infusions at 1mg/kg/dose monthly or a total dose of 6mg/kg. Chart review was done. Hand radiographs taken at baseline and after six months of therapy were reviewed by radiologist who was blinded, to determine metacarpal indices.

RESULT: There was an increasing trend in the metacarpal index from baseline to six months post-treatment with a mean difference of 0.053mm (CI -0.0112 to 0.117). However, the increase was not stastically significant (p value 0.0874) when analyzed using the paired t-test at a 95% confidence interval. No adverse events were noted and only one patient reported a fracture after starting therapy.

CONCLUSION: Bisphosphonate infusions among the six pediatric patients with moderate to severe osteogenesis imperfecta are well tolerate and although the increase in the metacarpal index from baseline after six months of treatment is not statistically significant, the trend shows improvement of the osteopenia from baseline.

Objective. To present preliminary data on the effects of intravenous pamidronate in children with moderate to severe Osteogenesis Imperfecta (OI). Methods. This is a restrospective study wherein a review of medical records and available serial radiographs of children (N=14) with moderate to severe IO started on pamidronate from 2006 to 2010 was done. Results. Two children have IO Type I, 8 have IO Type III and 4 have IO Type IV. At baseline, 2 had normal height, 8 had height less than minus 2SD and the rest with less than minus 1SD. Twelve out of 14 had vertebral compression fractures. Mean age at start of pamidronate was 5.4 years (range 0.5-11 years). First infusion fever in five patients and transient generalized macular rash in one child were noted. Serum calcium and phosphorus levels were normal at baseline and remained stable. Based on parental report, improvement of motor function was noted. In the 10 children who had at least a year of treatment, long bone fractures decreased from mean annualized fracture rate of 2.6 at baseline to 0.9. In patients with vertebral compression fractures, serial radiographs showed improvement of vertebral shape. Conclusion. This preliminary study shows that treatment was generally well tolerated and led to decrease in long bone fractures, improved vertebral shape and improved function.
Human ; Male ; Female ; Child ; Child Preschool ; PAMIDRONATE ; OSTEOGENESIS IMPERFECTA ; MUSCULOSKELETAL DISEASES ; BONE DISEASES ; BONE DISEASES, DEVELOPMENTAL ; BONE DISEASES, METABOLIC ; OSTEOCHONDRODYSPLASIAS ; THERAPEUTICS ; THERAPY ; OSTEOPOROSIS

Objective: Hydrops fetalis (HF) is a diagnosis with significant morbidity and mortality. It is the objective of this study to identify common etiologic causes of HF in the Philippine General Hospital (PGH). Methods: This is a retrospective review of hydrops fetalis cases delivered at the PGH from 2010 to 2014. There was a total of 75 identified cases of hydrops fetalis. However, only 58 of these, or 77.33% have available medical charts for review. Results: The median gestational age at birth was 31 (range 2140) weeks. There were 19 identified cases (32%) of stillbirth. Of the 32 patients born alive, 30 (93.75%) died in the immediate neonatal period. The etiologies of HF were identified in 15 cases, which included congenital anomalies (n=4), cardiac anomalies (n=3), infectious problems (n=3), hematologic anomalies (n=2), placental anomalies (n=2) and congenital tumor (n=1). Cases of congenital anomalies were only detected by congenital anomaly scan; no further work-ups were done. Fifteen (15) mothers presented with microcytic, hypochromic anemia on complete blood count (CBC). The cause of HF was not confirmed in the remaining 43 (74%) cases. Conclusion It is important to fully investigate the causes of HF to aid in the proper management and counseling. Further work-up must be done for mothers presenting with microcytic, hypochromic anemia. This is an important feature of alpha thalassemia. Partners of women suspected to have alpha thalassemia should also have a hematologic screening. The deletion of the four alpha genes will result to HB Bart’s hydrops fetalis; a major cause of hydrops fetalis in Southeast Asian countries.
Hydrops Fetalis

Objective: The study aimed to determine the prevalence of birth defects among neonates born at the Philippine General Hospital (PGH) from January 2011 to December 2014. Methods: Monthly censuses of all deliveries from January 2011 to December 2014 were obtained from the Section of Newborn Medicine. All deliveries with birth defects were coded using International Classification of Diseases-10 (ICD -10). The codes were tallied and classified as either an isolated, part of a recognizable syndrome, chromosomal syndrome or multi-malformed case (MMC). Period prevalence was then calculated. Results: There was a total of 20,939 deliveries from 2011 to 2014 in PGH, of which 574 babies (2.74%) had a diagnosis of at least one birth defect. Two-hundred seventy-three babies (47.56%) had isolated defects; 130 (22.65%) with defects in MMC; 106 (18.47%) with defects as part of recognizable syndromes; and 65 (11.32%) with defects as part of chromosomal syndromes. One in 36 births has at least one birth defect, which is higher than that reported in other Asian countries. Conclusion Birth defects are significant causes of morbidity and mortality. Results of this study provide baseline data that can be used for future studies on the causation of such birth defects, and can be used to formulate policies on primary and secondary prevention. For a tertiary hospital like PGH, these data can serve as a guide towards allocation of resources and manpower towards the more common birth defects.
Congenital Abnormalities

Haddad syndrome is a rare congenital disorder in which congenital central hypoventilation syndrome (CCHS) occurs with Hirschsprung’s disease. It is extremely rare with only more than 60 cases reported in the worldwide literature. We report on a Filipino newborn male infant who presented with signs and symptoms of progressive abdominal enlargement, bowel obstruction, and recurrent hypoventilation. The diagnosis of Haddad syndrome was made clinically and confirmed by sequence analysis of the PHOX2B gene which showed a 27repeat heterozygous expansion of the polyalanine-coding region. All CCHS patients require assisted ventilation especially during sleep to prevent lung atelectasis and other complications. An early diagnosis and confirmation by genetic testing is vital for proper management of affected patients.
Hirschsprung Disease

Background: Hemoglobinopathies as a group is one of the most common conditions confirmed through the newborn screening (NBS) program of the Philippines. This led to the increased participation of pediatric hematologists in the NBS program. Objective: The aim of the study was to assess newborn screening acceptance and knowledge of pediatric hematologists using an online questionnaire. Method: Members of the Philippine Society of Pediatric Hematology (PSPH), who are practicing pediatric hematologists in the Philippines, were invited to answer an online questionnaire. Results: Sixty members of the PSPH (65.2%) answered the survey. All the respondents are familiar with the newborn screening program. Fifty-seven respondents (95 %) have already managed a case of hemoglobinopathy identified through the newborn screening program. Differences in the approach to management and level of confidence with diagnostic test result interpretation have been noted. General themes of their concerns include being unaware of the protocol, concerns on delays in confirmatory tests, request for guidelines on follow-up, and incongruence of results with clinical picture. Conclusion The information collected may be used to develop strategies to better equip our pediatric hematologists and assist the PSPH standardize management protocols for hemoglobinopathies.
hemoglobinopathies ; newborn screening

Fibrodysplasia ossificans progressiva (FOP) is a debilitating, rare, autosomal dominant disorder of connective tissue characterized by malformed great toes and by progressive endochondral ossification of extra-skeletal sites (e.g., muscles, tendons, fascia) triggered by trauma, soft tissue injury, muscle fatigue, or viral infections. We present three children affected with FOP with this classic clinical presentation, the first reported cases in the Philippines, thus extending the range of classic FOP to new geographic and ethnic locations. Two of the affected children are siblings who have the common ACVR1 R206H mutation associated with classic FOP; this mutation was not found in their parents who are phenotypically unaffected, providing evidence of germline mosaicism in FOP. To our knowledge, this is the first family with genetic testing done showing presence of the classic mutation in affected siblings not seen in the unaffected parents.
Myositis Ossificans

Oromandibular Limb Hypogenesis Spectrum (OMLHS) [OMIM 103300] is a rare disease characterized by congenital defects of the face, mandible, tongue and hypoplastic limbs. The exact etiology remains unknown. We present two Filipino children diagnosed with OLMHS. Patient 1 is a 2-year-old female noted to have micrognathia, sygnathia and hypoplasia of distal extremities. Patient 2 is a 6-year-old male with hypoplastic mandible, micrognathia, micromelia of both lower extremities and syndactyly of hands. The early recognition of this disease is important so that early surgical correction of deformities particularly the hypoplastic mandible be addressed to avoid complications such as respiratory distress and feeding difficulties.
Ankyloglossia ; Hanhart syndrome