Aisha Alshdefat,Abdu Mueed Bidchol,Harshita Prabhakaran,Abdalla Alshdaifat

1Department of Maternal and Child Health,College of Nursing,Sultan Qaboos University,Sultanate of Oman; 2Genetic Reporting Manager,Al Ward Medical Services,Sultanate of Oman; 3Lecturer,Department of Maternal and Child Health,College of Nursing,Sultan Qaboos University,Sultanate of Oman; 4Medical Student,University of Lodz,Republic of Poland.

Abstract Larsen Syndrome is a rare inherited severe disease that described for the first time in the medical field as a distinct disease by Dr.Loren Larsen in 1950.It is characterized by congenital dislocation of multiple joints along with other anomalies, including heart, face, hands, and bones.We present a two years five months male who presented with facial dysmorphic features like low set of ears,depressed nasal bridge,micro-retrognathia,and broad forehead.

Keywords:Larsen Syndrome,inherited,newborn,distinct disease

Introduction

Larsen Syndrome is a rare inherited severe disease that described for the first time in the medical field as a distinct disease by Dr.Loren Larsen in 1950 [1].It is characterized by congenital dislocation of multiple joints along with other anomalies,including heart,face,hands, and bones [2].Larsen syndrome(OMIM#150250) is an uncommon but dangerous inherited defect of connective tissue formation that is transmitted in an autosomal dominant pattern [3].It is characterized by joint dislocation and flattened faces with a prevalence of 1:100,000.Larsen syndrome is caused by the Filmin B gene [4], which is integrated with cytoskeletal architecture, and carbohydrate sulphotransferase, which also involved other skeletal dysplasias [5].The presence of one copy of the changed Filmin B gene gene in each cell can cause the sign or symptoms of the Larsen syndrome[6].

Here we represent a 29 month- old male with a typical dysmorphic feature of Larsen syndrome,skeletal dysplasia, multiple contractures, chest deformity, smallmouth palate, and focal femoral deficiency.

Case report

A 29 months old male child born to a consanguineous couple.Hewas delivered by vacuum assistance due to fetal distress at 40 weeks of gestation from uneventful pregnancy.He was born with dysmorphic features like low set of ears, depressed nasal bridge,micro-retrocongnatheis,a broad forehead,overlapping fingers with the abnormal thumb of the hands, elbow joint contracture, bilateral congenital talipes equinovarus, long broad arteries, and patent foramen ovale,diagnosed as Larsen syndrome.

His physical examination was remarkable of dysmorphic features as described above,short neck,no torticollis, the scapula at same level but prominent to the left side, deformity in hand thumb, 30-degree flexion of the elbow,limited hip abduction but Barlows and ortolans test are negative, left knee has click(subluxation but very good range of motion), right thigh lateral distal small muscle), right knee is 90-degree flexion, the legs the same length, both feet bizarre with left side dorsiflexed and averted with contracted peroneus brevis and extensors, dorsal dislocation of the navicular over the talus, kyphosis and mild scoliosis of the spine,short neck,extra crease on the thigh, and deep hypo-plastic nails.Oral motor examination was the low tone at a check, limited tongue movement, no sign of a sensory problem, no jaw movement,and severe gag reflex.

Laboratory investigations; showed that the last Hemoglobin: 116.5, Thyroid Stimulating Hormone:5.84, Glucose-6-Phosphate dehydrogenase deficiency is normal, blood sugar 3.9 mmol.Brain and abdomen ultrasound are normal.

Echocardiography revealed small patent ductus arteriosus, patent foramen ovale, proper size ventricles with normal systolic function, no pericardial effusion,and rest heart structure and function are normal.

Brain ultrasound revealed normal midline structure, no hydrocephalous, no definite evidence on germinal matrix hemorrhage noted.

X-Ray skeletal showed that the right femur is shorted than size as compared to the left femur and can represent focal femoral deficiency.Furthermore,bilateral feet have deviated internally, skull unremarkable.

Audiometry test revealed normal hearing sensitivity on the right ear and moderate hearing loss on the left ear.While rare, Larsen syndrome patients may get hearing loss[7].

Currently, he has gross motor and fine motor delay,poor head holding and support,cannot roll over,cannot sit, cannot reach for objects but constant mouthing his thumbs.Thus he understands well and recognizes parents.

Recently, our patient admitted to the pediatric department with complaints of cough and cold for twelve days associated with fever; he was on antibiotics for five days as prescribed by a private doctor but still has fever and cough, medically impression of partially treated pneumonia.The patient's condition worsens to respiratory distress and respiratory failure requiring a maximum level of non-invasive ventilation with Fio2.On day two of admission, patient transfer to pediatric- ICU for intubation and ventilation.Difficult intubation with Endo Tracheal Tube size 3.5 mm cuff inflated on the second day of life because of subglottic stenosis; after one hour of intubation, respiratory acidosis was corrected,blood gases were PH:7.38,PCO2:48,HCO3:27, Lactate: 1.4.The patient extubated on day 14 of admission but re-intubated on day fourteen of hospitalization due to bronchospasm.On day 31 of admission patient tracheostomized due to failed extubation.

Currently, the patient doing well, not distress, chest X-Ray showed that bilateral equal air entry.The plan to follow with physiotherapists, occupational therapy,and spinal status should be monitored throughout his life.

Discussion

Larsen syndrome is an uncommon but dangerous inherited defect of connective tissue formation that is transmitted in an autosomal dominant pattern3.The etiology of Larsen syndrome is due to missense maturation in the FLNB gene.Diagnosis during the prenatal period can be possible at 18-20 weeks of gestation; ultrasound will show signs of Larsen syndrome is established through physical assessment,skeletal X-ray, and confirmed by genetic analysis.Management depends on the case of the patient;it may include orthopedic treatment and monitoring, surgical intervention for dislocation, monitoring the spinal status, dietary management, and physiotherapy.Larsen syndrome will not affect the intelligence, and the life expectancy of the child has this disease.

Conclusion and Recommendation

We presented this case to highlight the importance of timely detection of dangerous inherited defect of connective tissue formation that is transmitted in an autosomal dominant pattern.Such abnormalities that can be diagnosed during the antenatal period at 18-20 weeks of gestation,by ultrasonography leading to early management and intervention.