Dr Varsha v s, Dr C Jayakumar, Dr Praveena N Bhaskaran, Dr Navya George
AIMS Kochi.
Term male Ba of a non consanguineous parentage was delivered LSCS at 39 weeks of gestation.
Anomaly scans at 22 weeks of gestation was grossly normal with slight increase in diameter of posterior horn of lateral ventricles on the right side. Repeat scan showed , all long bones at or <5thcentile but no features of skeletol dysplasia Amniocentesis was done at 29weeks which showed normal fetal karyo type 30 weeks growth scan showed all long bones <5th centile. Esp the femoral length less than 2SD
Differentials
Familial short long bones,
Late onset nonlethal skeletal dysplasia. Scan done at 36 weeks skeeter further per growth of femur as – 4SD and all long bones <5th centile, so late onset non-lethal skeletal dysplasia was considered.
Ba’s had a weight of 2.90kg, Length of 46cm, head circumference of 36cm, chest circumference of 32cm, abdominal girth was 30.5cm. The upper segment to lower segment ratio was 1.97:1 . Physically ba had a large head with coarse facies (frontal bossing, depressed nasal bridge with mid face hypoplasia) with rhizomelic (proximal)shortening of UL and LL with trident hand. The tone of the ba was normal. Other systems were normal. Infantogram showed widening of both proximal and distal metaphysis of bilateral humerus and femur s/o metaphyseal flaring. B/L humerus and femur were shortened (rhizomelic shortening).
Metacarpals of both hands were short and of similar length with separation of middle and ring fingers (trident hand). Features were consistent with
Achondroplasia.
Parents have been counselled and Achondroplasia hotspot mutation genetic test has been send and was positive for Hetero c.1138G>A(p.Gly380Arg)in FGFR3 gene Hearing and vision were normal
Ba was active and feeding well at discharge.
Child is kept under close follow up and currently he is 7 months of age with anthropometric parameters of weight – 7 kg (b/w 0 and -2 SD) Length – 62 cm (below -3 SD) HC – 46.8 cm (between +2 SD and + 3 SD) MUAC – 15 cm.US/LS – 1.9.
Prevalence of achondroplasia approximately 1 in 20,000 live births and is the commonest bone dysplasia
This autosomal dominant condition caused pathogenic variants in the fibroblast growth factor receptor 3 (FGFR3) gene.
The most salient clinical features include disproportionate short stature (adult height is approximately 4 feet), long-bone shortening that predominantly affects the proximal aspects of the upper and lower extremities (rhizomelic shortening), and macrocephaly.
Patients with Achondroplasia may have delayed motor development early on, but cognition is normal.Approximately 80 percent of cases are the result of de novo pathogenic variants, while the remaining are inherited.
When both parents have Achondroplasia, the risk to their children of having homozygous Achondroplasia which is lethal is 25 percent and 50 percent of have Achondroplasia. Patients with Achondroplasia have gain-of-function variant in the FGFR3 gene. . This variant permanently activates the FGFR3 receptor, inhibiting chondrocyte proliferation, which ultimately leads to impaired endochondral bone formation, growth restriction, bone shortening, and other skeletal anomalies.
A well-known risk factor for Achondroplasia and other autosomal dominant conditions is advanced paternal age.
Deoxyribonucleic acid (DNA) replication defects in spermatogenesis is increased in males older than 45 years secondary to an increase in point mutations in the sperm.
Achondroplasia is characterized distinctive craniofacial features, disproportionate short stature with rhizomelic shortening of the arms and the leg, brachydactyly (shortening of the fingers and toes).Kyphoscoliosis and accentuated lumbar lordosis.
The craniofacial features and bone shortening are clearly present at birth. The nose is flattened out, often referred to as saddle nose deformity. The kyphoscoliosis can be seen from birth through infancy.
The lumbar lordosis is typically seen after ambulation starts at approximately 1.5 years of age.
Narrowing/stenosis of the craniocervical junction and the spine is variable in pediatric patients but has been reported in up to 50 percent of cases. Only a small number of those may require surgical correction.
The chest is often narrow.
The back displays kyphosis of the thoracolumbar junction, which is prominent during the first year of life and mostly resolves as the muscle tone improves, and ambulation starts.
Exaggerated lumbar lordosis is a common finding that becomes prominent after walking begins. The lumbar spine may become stenotic at a later age, typically not until after the second and third decades. The elbows may have limitations, primarily affecting extension and oftentimes limiting complete supination. The hands show short fingers with a trident appearance of the hands secondary to short metacarpal bones. Joint laxity is common. The knees often have varus deformities, initially due to joint laxity and later on secondary to tibial bowing and fibular overgrowth.
Prenatally, achondroplasia is suspected when shorter long bones and macrocephaly are present. Foetuses affected with achondroplasia born to average-stature females require caesarean delivery due to cephalopelvic disproportion.
Affected females with achondroplasia require a caesarean delivery when pregnant due to pelvic abnormalities.
The most useful radiographs are the anteroposterior (AP) view of the thorax and pelvis to look for the lack of widening of the interpedicular distances of the vertebral bodies, iliac abnormalities, and shortening of the long bones with metaphyseal abnormalities and hand films to look for shortening, brachydactyly, and trident deformity.
Parents should consult a geneticist
Complications associated with achondroplasia include recurrent otitis media, sleep-disordered breathing, obesity, leg bowing, narrowing of the lumbar spine, hypertension, and cervical medullary compression.
The management of achondroplasia focuses on maximizing functional capacity and monitoring, preventing, and treating complications.
An alternative approach is to correct the molecular defect and the developmental bone abnormalities caused the FGFR3 defects is under investigation.
Use of growth hormone is not recommended and can potentially worsen the disproportion seen in patients with Achondroplasia. Vosoritide, a recombinant C-type natriuretic peptide analog that stimulates endochondral ossification, a process that is inhibited in patients with Achondroplasia, is an option to increase linear growth in children with Achondroplasia ≥5 years of age whose epiphyses are still open.
Ilizarov (Limb lengthening surgery) is a method to increase the length of the long bones
The overall prognosis for patients with Achondroplasia is good unless they are affected with spinal compression of the cervical medullary junction, which is the most significant cause of morbidity and mortality in Achondroplasia. A vigilant follow-up of lumbar stenosis in older individuals is also required to avoid complications.
