Growth Pattern and Use of Inter-pupillary Distance in the Detection of Ocular Hypertelorism and Hypotelorism in Indian Down Syndrome Children

Use of inter-pupillary distance (IPD) for objective evaluation of ocular hypertelorism and hypotelorism is recommended to corroborate diagnosis of syndromic conditions. In view of complete absence of serial data on growth of IPD, this study aims to unfold auxological dynamics of IPD in Down syndrome (DS) children of Indian origin. Inner canthal distance (ICD) and outer canthal distance (OCD) were measured on a total of 1,125 (male: 752, female: 373) DS children, aged 0 to 3 months to 10 years at 6 monthly age intervals using a “Digimatic Sliding Caliper” in the Growth Laboratory/Growth Clinic of the Institute. Using Feingold and Bossert (1974) formula, IPD at each age was calculated from ICD and OCD measured among male and female DS children. IPD, like OCD and ICD increased un-interruptedly among DS children. IPD grew rapidly up to 5 years thereafter, its rapidity became slower. Boys in general, possessed larger IPD than girls, however, gender differences became statistically significant up to first 4 years of life. Our study children possessed significantly smaller IPD as compared with their normal Indian counterparts. None of our DS children depicted ocular hypertelorism while hypotelorism, was noticed amongst 4.9% male and 16.8% female DS patients. Comparison with normative IPD data failed to establish existence of ocular hypertelorism in DS children (<10 years) of north-western Indian origin. Use of age and gender-specific data presented for IPD of DS children may be made for comparative purpose to ascertain inter-population variability.

The First Vietnamese Patient of LEOPARD Syndrome due to a PTPN11 Mutation: A Case Report and Review of the Literature

LEOPARD syndrome is a rare congenital anomaly that involves several organs. Patients with this syndrome develop multiple lentigines resembling a leopard’s hide. LEOPARD is an acronym of the major features constituting the syndrome including lentigines, electrocardiographic conduction defects, ocular hypertelorism, pulmonary valve stenosis, anomalies of genitalia, retardation of growth, and deafness. The syndrome is rare, and only 200 cases have been reported yet worldwide. We present the case of an 8-year-old female patient who visited the Ho Chi Minh City Hospital of Dermato-Venereology because of multiple brownish-black “dots” on her face and body. On examination, she also showed abnormalities in the maxillofacial bones, vertebrae, shoulders, sternum, and teeth, as well as deaf-mutism and growth retardation, which are typical of LEOPARD syndrome. Genetic analysis revealed a PTPN11 gene mutation in this case. To the best of our knowledge, this is the first case of LEOPARD syndrome reported in Vietnam.

Leopard syndrome: the potential cardiac defect underlying skin phenotypes

LEOPARD syndrome (OMIM #151,100) caused by a germline PTPN11 mutation are characterized as multisystemic anomalies and variable marked phenotypes such as multiple lentigines and cafe´-au-lait spots, electrocardiographic conduction abnormalities, ocular hypertelorism/obstructive cardiomyopathy, pulmonary stenosis, abnormal genitalia, retardation of growth, and deafness. Phenotype overlap complicates clinical discrimination within RASopathies, making the diagnosis of LEOPARD more confusing and challenging. Besides, LEOPARD patients do not usually present with all these typical clinical features, increasing the possibility of underdiagnosis or misdiagnosis.Herein, we report a case of LEOPARD syndrome in a patient who only presented with pigmented skin spots and was initially diagnosed with multiple acquired melanocytic nevi. Subsequent pathological examination confirmed the diagnosis of multiple lentigines rather than melanocytic nevi. A genetic study showed a germline PTPN11 (Tyr279Cys) mutation and raised the suspicion of LEOPARD syndrome. A subsequent ECG examination detected potential cardiac defects and confirmed the diagnosis of LEOPARD. We considered that the potential damage of other systems underlying the skin multiple lentigines should not be ignored. The diagnosis of LEOPARD syndrome in an early stage before cardiac damage has reached a serious and irreversible stage can be meaningful for patients to fully understand the potential risks, complications and prognosis of the disease and to take appropriate precautions to prevent the potential risk of cardiac damage.

Tripod-shaped Syndactyly in Apert Syndrome with FGFR2 p.P253R Mutation

Apert syndrome is a rare acrocephalosyndactyly (craniosynostosis) syndrome characterized by craniofacial dysmorphism and syndactyly of the hands and feet. It is caused by FGFR2 mutations and inherited in an autosomal dominant manner. This article describes a novel clinical variant of Apert syndrome having bilateral symmetrical tripod-shaped syndactyly in hands with milder craniofacial features in a sporadic case, along with a mutation in the fibroblast growth factor receptor 2 (FGFR2) gene. The patient had shown craniosynostosis, dysmorphic face, ocular hypertelorism, marked depression of the nasal bridge, long philtrum, and low set ears. Direct resequencing of the FGFR2 gene through Sanger’s method identified a heterozygous missense mutation; FGFR2c.758C>G (FGFR2p.P253R) in the exon-7 of the gene.

An encounter with alobar holoprosencephaly: a case report

Alobar holopresencephaly is a rare embryonic condition where there is anomalous fusion of cerebral hemispheres. The key features include neurological impairment and facial dysmorphism like cyclopia, ocular hypertelorism with divided orbits and a proboscis. Obstetric ultrasound and foetal MRI are the diagnostic modalities. Majority of cases are sporadic in origin while a genetic association is also described. A small recurrence risk is noted in cases with sporadic origin. Early diagnosis and pregnancy termination are advisable for the condition since the survival rate is very low.

Deviation of paradigmatic mutations found in shprintzen-goldberg syndrome

Shprintzen-Goldberg (S-G) Syndrome known as rare congenital connective tissue disorder where craniosynostosis and marfanoid habitus found to be the usual presentation. Craniofacial dysmorphism with multi-organ involvement documented to be amongst prominent features of this syndrome. Case characteristics is five-month-old male infant with craniosynostosis, and motor developmental delay was evaluated for congenital connective tissue disorder. Dysmorphic craniofacial features like dolichocephaly, triangular forehead, ocular hypertelorism, micrognathia and retrognathia were noticed besides congenital umbilical hernia, empty scrotal sac, clinodactyly with long slender fingers, hyper-mobile joints, hypotonia. Subsequent investigations revealed normal male karyotype (46, XY) while genetic analysis depicted missense mutations in six different genes. Conventionally, mutation in SKI gene reported for its’ associated with S-G syndrome where dysregulation of TGF-β signaling was discussed as the primary reason. In the present case discussed here, it was found to have polygenic mutational association where few novel genetic mutations were seen.

21-week pregnancy with trisomy 18 (Edwards syndrome) − bone malformations highlighted

Edwards syndrome, also known as Trisomy 18 (T18) or Trisomy E, is a genetic disorder caused by the presence of all or part of an extra 18th chromosome. Some physical malformations associated with Edwards syndrome include small head (microcephaly) accompanied by a prominent back portion of the head (occiput); low-set, malformed ears; abnormally small jaw (micrognathia); cleft lip/cleft palate; upturned nose; narrow eyelid folds (palpebral fissures); widely spaced eyes (ocular hypertelorism); drooping of the upper eyelids (ptosis); a short breast bone; clenched hands; choroid plexus cysts; underdeveloped thumbs and or nails, absent radius, webbing of the second and third toes; clubfoot; and in males, undescended testicles. The diagnosis of Trisomy 18 is by ultrasound and amniocentesis, the fetal DNA being examined for genetic abnormalities. Therapeutic abortion can be done.

Apert syndrome: a case report

Apert syndrome was described as a triad of craniosynostosis, syndactyly and maxillary hypoplasia. The incidence of Apert syndrome is approximately one in 50,000 births. A three year old boy was brought with a history of facial, hand and feet deformities to the Pediatrics out patient department. On examination, he had symmetric syndactyly of the hands and feet. He also had craniosynostosis with deformed skull. This patient also exhibited midface hypoplasia, exophthahnia, ocular hypertelorism and high arch palate. Crowding of the teeth, malocclusion with anterior open bite is also found. The X-ray of the hand and feet showed skeletal fusion of phalanges (complex syndactyly). The case represents a rare condition where there is a mutation in the FGFR2 gene causing Apert syndrome.

Dermatologic Manifestations of the LEOPARD Syndrome

The LEOPARD syndrome is an exceptional autosomal dominant genetic disease with a missense mutation of the PTPN11 gene in more than 90% of the cases. The principal clinical manifestations include extensive lentiginosis, heart conduction abnormalities, hypertrophic obstructive cardiomyopathy, ocular hypertelorism, pulmonary stenosis, genital anomalies, mental retardation, growth retardation and deafness. A woman with a LEOPARD syndrome illustrates the progressive development of melanocytic nevi. In fact, the majority of lentigines are actually melanocytic nevi. Sequential digital dermoscopy evidences progressive growth of some melanocytic lesions. The ever-increasing number of melanocytic nevi in the LEOPARD syndrome is a risk factor for melanoma and full body photography and dermoscopy are recommended for follow-up.