advanced maternal age, at birth normal child

Amniocentesis due to advanced  maternal age; born after 39 weeks of gestation; Birth weight 2850g, length 46cm, head circumference 34cm, all around the 50th centile. Apgar score 9 , 10, 10. No congenital anomalies or dysmorphic features were noted. At age of six weeks, clinical examination indicated normal somatic and psychomotor development.

inv_dup(12)(pter→p13.32:
:p11.22→p11.22→q11:
:q11→p11.22::p13.32→pter) *

Child seen 3w after birth. With partial small bowel malrotation, hydrocephalus, macrocephaly infantile spasms, cortical visuals impairment, nasal dermoid on forehead, bifid uvula. At 3 y noted to have hypertelorism, downslanting palpebral fissure, short webbed neck, polythelia, 5th digit clinodactyly, hypotonia, inability to sit up without support. OFC in 25th centile. Profound developmentally delayed.

born at term, weight: 3.1 kg, APGAR  6 at 1 and 5 min. immediate respiratory distress, cyanosis, and hypoxemia. Congenital heart malformation was suspected Chest roentgenogram revealed dextrocardia, mild cardiomegalie, increased pulmonary venous marking, and left aortic arch (the major axis of the heart oriented from left shoulder to right hip, with the morphologic left atrium located to the left of the morphologic right atrium), obstructed infradiaphragmatic TAPVR to the portal vein/inferior vena cava, large secundum atrial septal defect, and patent ductus arteriousus. All the pulmonary veins coalesced behind the right atrium into a common pulmonary venous confluence, which drained to the portal system. Splenic tissue in the left upper quadrant suggesting abdominal situs solitus. After surgery,  secondary supraventricular tachycardia At 8 month  weight: 15th,  length: 50th centile, head circumference 15th centile; no developmental delay at this time.

born by cesarean section because placenta praevia, birth weight 3205g (50th centile), OFC 42.5cm (50th centile), no abnormality at birth noted; from birth on motor development delay retarded plus nystagmus; at 6m additionally noted hypotonia (esp. of trunk), decreases vision, nystagmus, alternating strabismus convergence; at 13m height 73cm (P10-P50), weight 9kg (P10-P50) OFC 45.2cm (P10-P50), plagiocephaly, protruding and low-set left ear, slight hypotonia; walking at 2y7m, speech severely delayed (at 3y only a few words); visual activity of 0.25 because of cerebral visual impairment; at 6y obesity  (height 117 (P25), weight 29.4kg (3kg > P98), severe flat feet, speaking only single words and 2-word sentences.

normal at birth; sSMC missed in prenatal diagnosis, which was done due to advanced  maternal age; at 6m motor retardation, poor visual contact, hypotonia, plagiocephaly, decreased vision, horizontal nystagmus

Uneventful pregnancy; born at term by cesarean section due to uterine inertia. Weight: 3520g; length 51cm; OFC 33cm; At birth. anorectal malformation with urethral fistula; skeletal X-ray showed multiple dorsal and lumbar hemivertebrae, sacral agenesis, multiple fused ribs; medullar lipoma; thickened terminal filum, hydromelia; absence of left kidney; normal psychomotor development

Pregnancy and delivery normal, at birth weight 3485 g, APGAR score 7-9-10. Dysmorphic bilateral optic disc coloboma, small chin, broad mouth, large tongue, angulated ears, pronounced nuchal skin folds and bilateral partial syndactyly of second and third toes, patent ductus arteriousus, mildly reduced myocardial contractility. Brief myoclonic spasms in lower extremities observed 1month after birth. Shortly after this, generalized tonic-clonic seizures. The electroencephalogram was normal and computed tomography showed no radiological abnormalities of the brain and skull. Swallowing was difficult and there was hypertonia of lips and cheeks. At 15m received a percutaneous endoscopic gastrostomy. Weight and head circumference are within normal limits, whereas height is more than 3 SD above normal. She still often falls to one side when sitting, she can stand only when held and helped, does not yet walk and has mild flexion contractures of her knee joints

Birth weight was 3.1 kg, length 50 cm and head circumference 35 cm. He presented mild retrognathia, feeding problems with poor sucking; psychomotor development retarded with delayed visual maturation; able to walk without support at the age of 18 months; At 2.5y psycho diagnostic testing revealed severe developmental delay (developmental level of 12 months at the age of 30 months) with autistic behavioral features; at age of 5y 4m severely mentally retarded; weight 17 kg (25th percentile), height 102 cm (third percentile); HF 48.8 cm (third percentile); general physical development is adequate; mild facial dysmorphism with large mouth, full lips, relative midface hypoplasia, small and conical teeth; except for two extra nipples on the right side and one on the left side, no other congenital malformations are present. Routine biochemical and metabolic screening and brain MRI scan are normal.

second child of non-identical twins, born in week 37 of gestation; failure to thrive, recurrent respiratory tract infections, developmental delay, atrial septum defect, dysmorphic features like prominent metopic suture, down slating palpebral fissures, low set ears, long slim digits; weight and length <0.4 centile; OFC~3rd centile; 

2y

7y

see McCl-12-Up13.1/1-1

craniofacial abnormalities (convex forehead, micrognathia, abnormal left ear), severe hypotonia, growth delay

psychomotoric delay, dysmorphic features like macrocephaly, agenesis of corpus callosum, high and prominent forehead, hypertelorism, dysplastic ears, cleft palate, uvula bifida, zygodactyly of 2. and 3. toes and hearing impairment

mar(12)

global developmental delay; coarse facies, plus other dysmorphic features as seen on PKS; bifrontal sparseness of hair, abnormal placed prominent ears, mild hypertelorism, upslanting palpebral fissures, epicanthic folds, flattened nasal bridge, long philtrum, high arched palate

ATYPICAL ACENTRIC PKS MARKER

inv dup(12)(pter→p13::p13→pter)

Pregnancy and term delivery were normal. Birth weight 3.850 g (90th centile), length 53 cm (90^th centile), head circumference 34 cm. No perinatal problems were noted; referred to a children’s hospital because of psychomotor developmental retardation; began sitting with assistance at 8 m and walking at 1 y 9 m; motor activity decreased; she presented with mental and speech delay; at 2 y 2 m weight 16.2 kg (97th centile), length 89 cm (75th centile), OFC 47.5 cm (10th - 25th centile); there was paratrophia (unusual for the age fat accumulation on buttocks and hips) and muscular hypotonia. Craniofacial dysmorphism included hypotrichosis (sparse scalp hair), a high forehead with high frontal hairline, mildly dysmorphic longish ears with hypoplastic antihelices and lobes, a round face, flat supraorbital regions, mild hypertelorism (3.2 cm), horizontal position of eye axes, flaring of lateral part of eyebrows, long straight eyelashes, a large nose with bulbous tip, full lips, short upper lip with short frenulum, high-arched palate, unusual configuration of both eyeteeth; broad neck, chest deformation (marked prominent of parasternal regions) and pilonidal dimple. Hands and feet were large with mild swelling of the dorsa as well as flat arches of the feet. At the age of 10 years: weight 46.5 kg (>97th centile), length 158 cm (>97th centile), OFC 52 cm (50th centile), profound mental delay, lack speech and self-help skills, behavioral abnormalities (irritability, aggressiveness) and abnormal gait, still muscular hypotonia and an unusually slow hair growth with sparsity of scalp hair bitemporal. At 12 10/12 y normal pubertal development with regular menarche, chronic rhinitis and caries. Hematological studies revealed a persistent leucopenia (first appeared at the age of 11.5 y).

inv dup(12)(pter→p12.3: :p12.3→pter) 

third child of healthy non-consanguineous parents, uneventful pregnancy, delivery spontaneous at term (birth weight 3.300g (50th centile), length 49cm (25th centile), head circumference (OFC) 33cm (10th centile), APGAR scores 10/10/10). At age of  1 month : apparent dysmorphic signs, heart murmur, hypotonia. Weight, length and OFC between the 3rd and 7th centile. Anomalies: bitemporal sparsity of hair, narrow prominent forehead, small ears, ptosis, hypertelorism, broad flat nasal bridge, small nose, long philtrum, thin upper lip, drooping lower lip and high arched palate. She had broad hands with terminal hypoplasia of fingers., apparently narrow pulmonary artery, slight supraventricular stenosis; small posterior-apical situated atrial septal defect. Diagnosis of PKS (Fig. 1).  Seizures have been present since the age of 3 years. 

inv dup(12)(pter→p12.3: :p12.3→pter) 

sonographic abnormalities; left hydroureter, left hydronefrosis

in fibro: 47,XY,+mar[18]/
46,XY[32]

inv dup(12)(pter→p11.22: :p11.22→pter) 
buccal mucosa nuclei:
sSMC in 53%

Normal pregnancy and delivery; birth weight 4940 g (>97th centile), length 53 cm (90th centile), OFC 'normal'. At 6m  psychomotor delay. At 2.5 y weight 13 kg (50th centile), length 87 cm (50th centile), head circumference 46cm (<3rd centile). Dysmorphic features incl. patchy front temporal alopecia, hypertelorism, long philtrum, low set posteriorly rotated ears, anteverted nostrils, epicanthal folds, bilateral simian crease, hypo pigmented skin whorls on trunk and limbs. Plus horizontal nystagmus, bilateral sensorineurak hearing loss, generalized muscular hypotonia, severe psychomotor retardation, speech absent. PKS like.