Routine prenatal ultrasound evaluation may reveal traits such as abnormal presentation close to due date, rhizomelia, diaphragmatic abnormalities such as hernias, anal defects, and heart malformations, especially ventricular septal defect, all of which are highly suggestive of this syndrome.

After birth, the first sign that draws the clinician's attention is hypotonia, that may be severe enough to interfere with respiration and deglutition. Newborns and children also have a specific phenotype, characterized by facial dimorphism: "coarse" facies, high forehead, sparse lashes and eyebrows, shallow supraorbital ridges, hypertelorism, flat nasal bridge, long philtrum [1], short neck, low-implanted ears, large tongue, hypoplastic nails and small hands, sparse hair and areas of unusual skin pigmentation [2]. The hypotonia persists as the child grows older, leading to difficulties in sitting, standing, and mobility. The clinical picture is completed by intellectual disability, manifested as severe or profound mental deficiency, deafness, seizures, hypoplastic lungs and speaking difficulties. Other abnormalities such as cleft palate, supernumerary nipples, genital malformations, auditory canal stenosis, extra fingers or toes or bald scalp areas may also occur. The neurologic prognosis of these patients is grim, with severely disabled motor capabilities and incontinence [3] [4].

Diaphragmatic hernias are considered to be highly specific and are frequent [5].

These traits may not be present in all affected individuals or may be less prominent. The severity of genotype abnormalities does not correlate with the clinical features of the newborn [6]. In other cases, different sides of the body may be affected unevenly.

• Coarse Facial Features

  The clinical symptoms associated with this condition were first recognized in 1977, when Pallister described two adults, aged 19 and 37, who had profound retardation, severe hypotonia, coarse facial features, and pigmentary abnormalities. [mhmedical.com]

  Systemic features in childhood are numerous and variable, and include most frequently "coarse" facial features, midface malformations, psychomotor delay, hypotonia, scalp hair sparsity, and variegated lightly and darkly pigmented skin.1-9 We describe [jamanetwork.com]

  facial features as child gets older, broad nasal bridge, streaks or patches of lighter or darker skin, sparse hair or bald patches, high arched or cleft palate, shorter arms and legs, disproportionate to the body and extra nipples. [dailymail.co.uk]

• Short Finger

  The dysmorphic features included a board forehead with high anterior hairline, hypertelorism, flat nasal bridge, short upturned nose, down turned corners of the mouth, short fingers, single transverse crease in the right hand, and hypotonia. [ashg.org]

  […] bulging out Prominent eyes Prominent globes Protruding eyes [ more ] 0000520 Pulmonary hypoplasia Small lung Underdeveloped lung [ more ] 0002089 Renal cyst Kidney cyst 0000107 Renal dysplasia 0000110 Seizures Seizure 0001250 Short phalanx of finger Short [rarediseases.info.nih.gov]

• Single Transverse Palmar Crease

  transverse palmar crease 0000954 Small scrotum Underdeveloped scrotum 0030276 Somatic mosaicism 0001442 Sparse anterior scalp hair Sparse scalp hair at front of head Thin scalp hair at front of head [ more ] 0004768 Sparse eyelashes Scant eyelashes Scanty [rarediseases.info.nih.gov]

• Failure to Thrive

  Her growth curve is below the third centile, indicating failure to thrive. She has global delay in development and is presently attending the Early Intervention Program for Infants and Children at a special school. [nature.com]

• Macroglossia

  The disorder in older children and young adults is characterized by a coarse and flat facies, macroglossia prognathia, everted lower lip, and severe psychomotor retardation with muscular hypertonia and contractures. [ncbi.nlm.nih.gov]

  Macroglossia and pointed chin occur with age. Hypotonia is present at birth with contractures developing with age. A wide range of congenital malformations may be present, the most specific being diaphragmatic and anal defects. [orpha.net]

  CASE REPORT: A 5-year-old male patient with typical PKS characteristics (facial dimorphism, temporal alopecia, micrognathia, macroglossia, mental retardation, seizures and pigmentary skin lesions) was scheduled to magnetic resonance of the head under [scielo.br]

  As patients pass into adolescence, the syndrome is characterized by a coarse and flat face, macroglossia, prognathism, inverted lower lip and psychomotor retardation with muscular hypertonia and contractures. [popflock.com]

• High Arched Palate

  Oro-dental features, such as "Pallister lip," macroglossia, delayed eruption of primary teeth, high arched-palate, prognathism, and cleft palate have been occasionally reported in the medical literature. [ncbi.nlm.nih.gov]

  PKS has the following characteristics: low muscle tone facial features that are common to the syndrome-high forehead, broad nasal bridge, wide space between the eyes sparse scalp hair at birth high, arched palate hypopigmentation extra nipples cognitive [pkskids.net]

  arched palate or cleft palate hypopigmentation cognitive and developmental delays diaphragmatic hernias(about 40%;this potentially serious birth defect allows the stomach and intestines to move into the chest, where they can crowd the developing heart [physio-pedia.com]

  The facial appearance includes coarse facies (coarseness becomes more pronounced with age), prominent forehead, hypertelorism, upslanting palpebral fissures with epicanthal folds, small nose with upturned nares, high arched palate, macrostomia, long philtrum [molecularcytogenetics.biomedcentral.com]

• Macrostomia

  The syndrome presents with a recognizable pattern of findings including: pigmentary skin changes, characteristic facial features (sparse anterior scalp hair, flattened midface, macrostomia, and coarsening of the facial features), and developmental delay [ncbi.nlm.nih.gov]

  The facial appearance includes coarse facies (coarseness becomes more pronounced with age), prominent forehead, hypertelorism, upslanting palpebral fissures with epicanthal folds, small nose with upturned nares, high arched palate, macrostomia, long philtrum [molecularcytogenetics.biomedcentral.com]

• Dry Skin

  The girl has woolly and sparse hair, absence of lateral eyebrows, dry skin, brittle nails, hypopigmented patches, frontal bossing, hearing loss, hypertrophic dilated cardiomyopathy, polydactyly, and mild developmental delay. [ncbi.nlm.nih.gov]

• Hearing Impairment

  Vision and hearing impairments may occur. Patients may also exhibit congenital heart defects, gastroesophageal reflux, cataracts and supernumerary nipples. Diaphragm problems are also possible. [popflock.com]

  Vision and hearing impairments may occur. Patients may also exhibit congenital heart defects, gastroesophageal reflux, cataracts, and supernumerary nipples. Diaphragm problems seen in newborns can lead to death shortly after birth. [wikidoc.org]

  impairment Deafness Hearing defect [ more ] 0000365 Hyperpigmented streaks 0007572 Hypertonia 0001276 Hypertrophic cardiomyopathy Enlarged and thickened heart muscle 0001639 Hyperventilation Rapid breathing 0002883 Hypopigmented streaks 0007535 Hypoplastic [rarediseases.info.nih.gov]

  impairment Underdeveloped or improperly developed genitals Gastrointestinal defects, abnormal kidney function Reduced growth of head size and body length Severe mental retardation Severe heart defects Hip dislocation at birth, abnormally curved spine [dovemed.com]

• Epicanthal Folds

  folds large ears with lobes that are thick and protrude outward. [en.wikibooks.org]

  Patients also exhibit a distinctive facial structure, characterized by high foreheads, sparse hair on the temple, a wide space between the eyes, epicanthal folds and a flat nose. Vision and hearing impairments may occur. [popflock.com]

  Other ocular abnormalities overlap with those of PKS (Table 1), and include strabismus, hypertelorism, epicanthal folds, scleralization of the cornea, iris heterochromia, and microphthalmia. The karyotype in hypomelanosis of Ito is normal. [jamanetwork.com]

  Patients also exhibit a distinctive facial structure, characterized by high foreheads, sparse hair on the temple, a wide space between the eyes, epicanthal folds, and a flat nose. Vision and hearing impairments may occur. [wikidoc.org]

• Hypertelorism

  We showed that the most consistent pre-natal ultrasound findings include hypertelorism, broad neck, shorts limbs, abnormal hands or feet, diaphragmatic hernia and hydramnios. [ncbi.nlm.nih.gov]

  Seizures and developmental delay Callosum disgenesy, shortage white matter, rarefied myelinization, kyphosis 3 Male 36y /43y Hypertelorism, flat, broad nasal root, anteverted nostrils, thin upper lip, high-arched palate Normal Inguinal and umbilical [molecularcytogenetics.biomedcentral.com]

  Craniofacial manifestations include a coarse'' face with flat profile, high forehead with temporo-frontal balding, sparseness of eyebrows and lashes, shallow supraorbital ridges, upslanting palpebral fissures, hypertelorism, flat and broad nasal bridge [orpha.net]

• Broad Nasal Bridge

  Craniofacial manifestations include a coarse'' face with flat profile, high forehead with temporo-frontal balding, sparseness of eyebrows and lashes, shallow supraorbital ridges, upslanting palpebral fissures, hypertelorism, flat and broad nasal bridge [orpha.net]

  Subsequent interphasic FISH with a centromeric probe detected tetrasomy 12p in mosaic.The postnatal phenotype of PKS is quite severe and include coarse facies with a high forehead, sparce scalp hair, hypertelorism, broad nasal bridge, hypotonia, streaks [fupress.net]

  PKS has the following characteristics: low muscle tone facial features that are common to the syndrome-high forehead, broad nasal bridge, wide space between the eyes sparse scalp hair at birth high, arched palate hypopigmentation extra nipples cognitive [pkskids.net]

  Major symptoms may include a coarse face with a high forehead, sparse hair on the scalp, an abnormally wide space between the eyes, a fold of the skin over the inner corner of the eyes, and a broad nasal bridge with a highly arched palate. [rarediseases.org]

• Short Neck

  Here, we report on an unusual case of i(12p) in a 15-year-old boy presenting with mild mental retardation, minor facial features (long face, prognathism, short neck), normal weight, length, and OFC parameters as well as hyperpigmented streaks. [ncbi.nlm.nih.gov]

  Newborns and children also have a specific phenotype, characterized by facial dimorphism: "coarse" facies, high forehead, sparse lashes and eyebrows, shallow supraorbital ridges, hypertelorism, flat nasal bridge, long philtrum, short neck, low-implanted [symptoma.com]

  neck [ 8, 9 ]. [synapse.koreamed.org]

  neck A number of other clinical features can help identify PKS. [forgottendiseases.org]

  neck (OMIM #601803; ). [dx.doi.org]

The diagnosis relies on the detection of the mosaic tetrasomy of isochromosome 12p. This can be done by various techniques, performed on different cell types. The most reliable choice is to perform an amniocentesis, as i(12p) is found in all amniocytes in fetuses suffering from this condition [7]. Similarly, all newborn bone marrow cells have this trait [8], whereas a variable percentage of fibroblasts, lung, liver, testes and spleen cells exhibit the abnormality, hence the "tissue-specific mosaicism" term. Lymphocytes are infrequently affected, therefore blood karyotype may not be a reliable method to diagnose this illness, especially due to the high turnover of blood cells. Fibroblasts may be obtained from buccal smears or skin areas with different pigmentation. The percentage of i(12p) cells does not correlate with disease severity [9]. Furthermore, the number of detectable diseased cells decreases as the patient ages [10].

Fluorescence in situ hybridization (FISH) [11] [12] and interphase FISH are reliable diagnostic methods [13]. Other methods include karyotype analysis, array comparative genomic hybridization (CGH) and chromosomal microarray. A normal karyotype of blood cells does not exclude the diagnose. In case clinical doubt persists, newer diagnostic methods, such as spectral karyotyping and multiplex-FISH may shed light over the case [14].

• 3 Hz Spikes

  Renzo Guerrini, Michelle Bureau, Marie‐Geneviève Mattei, Agatino Battaglia, Marie‐Claude Galland and Joseph Roger, Trisomy 12p Syndrome: A Chromosomal Disorder Associated with Generalized 3‐Hz Spike and Wave Discharges, Epilepsia, 31, 5, (557-566), (2007 [doi.org]

• Hypsarrhythmia

  Intractable epileptic spasms developed 17 months after birth, and electroencephalography revealed a modified hypsarrhythmia. The seizures were uncontrollable with sodium valproate monotherapy. [ncbi.nlm.nih.gov]

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