A 1.1-year-old boy was referred to our clinic for genetic evaluation, because of his growth retardation. The boy is the second-born of nonconsanguineous parents. He was born at 39+1 weeks of gestation and birth weight 3.15kg, birth length 49cm, head circumference 34.5cm. There is no history of neonatal asphyxia, but Apgar values were not available. After birth, the boy was mixed feeding, and had no feeding difficulty. Physical development lagged compare with typically developing peers. His growth rate was about 9.5cm in his first year of life, and He cannot sit by himself at the age of 1.1y. His language development was within normal range. Hydrocephalus was found at the age of 6 months, but untreated. There was no history of similar diseases in the family. His father is 162cm, his mother is 153cm, both are healthy. And he has a healthy sister age 10y.
Physical examination: Ht :58cm (-7SD), Wt: 5.2kg (-5SD), head circumference: 50cm (+2SD), skin eczema, hair and eyebrow are thinning, left upper eyelid ptosis, Long eyelashes, high arched palate, prominent forehead, pectus carinatum(the prominent sternum), short limbs, deep palmar crease, joint hypermobility. No obvious abnormalities in spine.
The main laboratory examination: blood and urine routine tests, liver and kidney function, electrolytes, serum electrolyte, thyroid function, and blood tandem mass spectrometry test were normal. Growth hormone (GH) stimulate test: GH peak is 1.19 ng/ml(＞10ng/ml). IGF-1: 51.9 ng/ml(55-327ng/ml). No pathogenic variation was observed in the FGFR3 gene sequencing analysis and micro-array test. Echocardiographic: ventricular septal hypertrophy，9.7mm(＜ 8mm). Electrocardiogram indicated high left ventricular voltage. Cranial MRI: external hydrocephalus in the frontotemporal region. X-ray: osteoporosis, bone age was behind his peers, the spine was slightly scoliosis.
Follow-up: We keep intermittent following this patient for 6 years. And his ventricular septal was gradually increasing, the thickness of ventricular septal was 12mm at the age 3y. Cardiologist suggested Beta receptor blockers for oral medication at that time, but his parents did not adherence to the medication. Interesting, the thickness of his ventricular septal did not increase during the following examination at the age of 4y, even after the six-month GH treatment. He was under six month GH treatment with dosage of 0.1 IU/kg/d，and was benefit 4cm during the therapy. The growth chart of the patients was in Figure 1-A. At the age of 5y, he had bleeding caused by gastric ulcer after oral antipyretic, and then had partial gastrectomy.
A 1.8 years old boy was referred to our clinic because of his growth retardation, mild high lactic acid and cryptorchidism. He was the first-born child of his family, his birth weight was 3.03kg, birth length was 49cm. He had no feeding difficulties in neonatal period. Physical development lagged compared with typical developing peers, but language development was similar to typical developing peers. Mild elevated blood lactic acid and hypoglycemia were found in his health examination. His father is 160cm and his mother is 155cm. They are physically healthy and has no history of the hereditary disease.
Physical examination: Ht :68.5cm (-5.6SD), Wt :7.6 kg (-4SD), head circumference 49.8cm (+2SD), skin eczema, the color of the skin was darker than his parents, fluffy hair, prominent forehead, sparse eyebrow, long lashes, joint laxity, cryptorchidism, normal penis, deep palmar crease.
The main laboratory examination : Blood glucose: 3.34mmol/L (3.9-6.2 mmol/L); lactic acid 1.8-2.8 mmol/L (0.5-1.6 mmol/L), fasting insulin: 12.2 (fasting 17.8-173 pmol/L). Blood gas analysis test, blood and urine routine tests, liver and kidney function, electrolytes, serum electrolyte, thyroid function, and blood tandem mass spectrometry test were normal. Growth hormone (GH) stimulate test: GH peak 2.35 ng/ml(＞10ng/ml). IGF-1 50 ng/ml (55-327ng/ml). The blood tandem mass spectrometry (amino acid and fatty acid analysis), urine organic acid test, microarray, and FGFR3 gene sequencing were normal. Cranial MRI: The brain volume was larger than the same age peer. Bone age was delayed. Scrotum ultrasonography showed both testicles were in the groin area. X-ray of spine, echocardiographic and electrocardiogram were normal.
Follow-up: We keep following this patient for 5 years. The blood lactic acid was within normal range several times. He started GH treatment (0.1IU/kg/d)from 3y old, and gained 6.2cm/7month, then stopped treatment by the parents without doctor’s suggestion. When stop the GH treatment, his growth velocity was slower down. The growth chart of the patients was in Figure 1-B. There was no skeleton or cardiac anomality observerd during the follow-up period.
A 2 months old girl was referred to our department because of her poor growth. The girl was the second child the family. During the pregnancy, there was complicated by polyhydramnios. She was born full-term, birth weight was 3.4kg, birth height was 50cm. The Apgar score were 10 - 8 - 9 -9. She had feeding difficulty and malnutrition, growth retardation, poor motor development, recurrent skin eczema and respiratory infections. The parents are healthy, and they are not consanguineous, without remarkable family history. She has a 4 years old brother, who is normal in growth and development. The girl was admitted to hospital because of pneumonia.
Physical examination: HT:50cm(-3SD), WT:3.98kg(-2SD), head circumference:41.5cm(+2SD), temperature:37.8℃, pulse:172times/min, respiratory rate:50 times/min, blood pressure:70/48mmHg, scaphocephaly, anterior fontanelle: 4*4cm flat and soft, prominent forehead, esotropia, micrognathia, high palate, muscular hypotonia, joint laxity, sparse scalp hair and eyebrow. A mass was touched about 4*4cm in the left epigastric.
The main laboratory examination: blood glucose: 3.7mmol/L, blood routine and hyper-sensitive C-reactive protein suggest she had an infection. Digital radiography (DR) of the thoracic chest indicates she had pneumonia and increased heart shadow. cranial ultrasound: subependymal hemorrhage, Echocardiography: patent foramen ovale, mild abnormality of the pulmonary valve. abdominal ultrasonography: mixed echogenic mass (4.0*3.6cm) in left abdomen, low echogenic mass (5.6*2.9*3.8cm) in the left lobe of the liver. That may be a hemangioma. Upper gastrointestinal opacification: descending colonic dilatation, upper-Abdomen routine, and enhancement scanning: multiple hemangiomas in the liver, cranial MRI: Abnormal structure of gyrus in the right frontal lobe. The result raises the possibility that pachygyria. Neonatal neurobehavioral score 31 points (not pass). Qualitative general movements assessment（GMS）: GMs (poor repertoire), term infant.
Follow-up: We keep follow-up this girl for 2.5 years. Now she is 2.5y, 76cm(-5SD),8.5kg(-4SD). She can stand and walk for while by herself. X-ray of spine and echocardiography were normal.