Table 4.

Chromosome Anomalies Associated With Congenital Diaphragmatic Hernia and Additional Major Malformations/Dysmorphology

Chromosome AbnormalityCritical Genes IncludedFacial PhenotypeOther Clinical Characteristics (in addition to CDH)
Pallister-Killian syndrome (PKS) 1 (mosaic tetrasomy 12p) (OMIM 601803)
  • Coarse w/wide-set eyes, prominent cheeks, & eversion of vermilion of lower lip
  • Considered similar to Fryns syndrome 2, 3
  • Sparse hair, 4 syndactyly, & streaky skin pigmentation
  • Hypotonia, seizures, & ID common 3
  • Short distal phalanges of fingers & toes, small nails, cloudy corneas, CHD, & internal malformations may be seen but are typically less frequent in PKS than in Fryns syndrome.
Del 15q26.2 (OMIM 142340)NR2F2 5Fryns syndrome-like craniofacial anomaliesCHD, hypoplastic genitalia or cryptorchidism, severe prenatal growth deficiency, ID, talipes equinovarus &/or rockerbottom feet, single umbilical artery
Del 8p23.1 (OMIM 222400)GATA4
SOX7 5		Mild facial anomaliesCHD (e.g., heterotaxy), renal anomalies, ID
Del 8q22-q23ZFPM2 5Blepharophimosis, widely spaced eyes, epicanthus, flat malar region, thin vermillion of upper lip, downturned corners of mouth, ↓ facial movementID w/absent speech, microcephaly, seizures, growth delays 6
Del 1q41-q42 (OMIM 612530)HLX
DISP 5		Limb anomalies (e.g., talipes), cleft lip & palate, seizures, ID
Del 15q24 (OMIM 613406)Typical craniofacial featuresMalformations of hands & feet, growth delays, ID w/marked speech delay
Del 4p16.3 (OMIM 194190)FGFRL1 5Typical facial anomalies assoc w/Wolf-Hirschhorn syndromeSkeletal anomalies, ID, growth delays
Del 22q11.2Typical facial anomalies assoc w/22q11.2 deletion syndrome, cleft palate
  • CHD, skeletal anomalies, hypocalcemia
  • CDH is present in 0.8% of persons w/22q11 deletion. 7
Del 17q12Facial anomalies (See 17q12 Recurrent Deletion Syndrome.)MODY, cystic renal disease, pancreatic & liver abnormalities, macrocephaly, ID 8

AD = autosomal dominant; AR = autosomal recessive; CDH = congenital diaphragmatic hernia; CHD = congenital heart defect; ID = intellectual disability; MODY = maturity-onset diabetes of the young

1.
2.

In some persons, only chromosome analysis and/or the inheritance pattern can distinguish between PKS and Fryns syndrome [Veldman et al 2002]. To evaluate for PKS, skin fibroblasts, chorionic villus cells, or amniocytes should be karyotyped because of the phenomenon of tissue-specific mosaicism in which the isochromosome 12p can be present in some cells (e.g., fibroblasts), but not others (e.g., lymphocytes). It is important to note that a normal karyotype or CMA on peripheral blood lymphocytes does not exclude PKS, although CMA may detect PKS when the percentage of tetrasomic cells is relatively high.

3.
4.

Sparse hair is characteristic of PKS, in contrast to Fryns syndrome, in which the sisters originally described by Fryns had low hairlines and hypertrichosis.

5.
6.
7.
8.

From: Fryns Syndrome

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