The infant presented in the above clinical case had novel homozygous mutation in PYCR1 gene which is likely pathogenic variant of autosomal recessive cutis laxa type 2B/3B [3]. PYCR1 gene helps in synthesis of proline from glutamate. [link.springer.com]

Novel Insights • The 2 related patients described here are the first prenatal presentations of ARCL1B. [karger.com]

The specific symptoms present, severity and prognosis can vary greatly depending upon the specific type of cutis laxa and the presence and extent of associated symptoms. [rarediseases.org]

Follicular hyperkeratosis was present on cheeks, preauricular, temporal, and submandibular areas with a background of erythema and brownish pigmentation similar to Erythromelanosis follicularis faciei et colli. [journals.lww.com]

Present is a mutation at the PYCR1 gene (pyrroline-5-carboxylate reductase 1 - gene location 17q25.3), a protein-coding gene encoding an enzyme of the same name localized in the mitochodria that catalyzes the NAD (P) H-dependent conversion of pyrroline [altmeyers.org]

• Developmental Delay

  Hypotonia, developmental delay, and intellectual disability are common. In addition, cataracts, corneal clouding, wormian bones, lipodystrophy and osteopenia have been reported. [mendelian.co]

  Global developmental delay MedGen UID: 107838 •Concept ID: C0557874 • Finding A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social [ncbi.nlm.nih.gov]

  Most affected children have malformations of certain areas of the brain (cortical and cerebellar malformations) that result in delays in reaching developmental milestones (developmental delays) and intellectual disability. [rarediseases.org]

  Developmental delay can be observed in the majority of the children, partially due to muscle hypotonia and to some degree hyperflexible joints. [nature.com]

• Failure to Thrive

  […] to thrive growth retardation, poor growth joint hypermobilty, dislocations, laxity microcephaly (<2 SD for age) onset, infancy onset, neonatal skin hyperelasticity visible veins [metagene.de]

  Failure to thrive MedGen UID: 746019 •Concept ID: C2315100 • Disease or Syndrome Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. [ncbi.nlm.nih.gov]

  […] to thrive Micrognathia Abnormal facial shape Epicanthus And another 39 symptoms. [mendelian.co]

  Infants may experience diminished muscle tone (hypotonia), abnormal fat distribution, feeding difficulties, growth deficiency, and failure to thrive. [rarediseases.org]

  The neonate had transient feeding problems and failure to thrive. At the age of 6 months, she had a normal stature (69 cm: −1.5 SD) but low body weight (6.9 kg: −2 SD) and mild microcephaly (−2 SD). [nature.com]

• Alopecia

  Symptoms include an abnormally large head (macrocephaly), partial or complete hair loss (alopecia) and the skin symptoms of cutis laxa. Cutis laxa is mild with redundant skin on the face the most common manifestation. [rarediseases.org]

  Whereas macrocephaly, alopecia, cutis laxa, and scoliosis syndrome (MACS, OMIM 613075) is caused by mutations in RIN2. ARCL2A, ARCL2B, and GO manifest with many of the same features, making a definitive clinical diagnosis difficult. [mdpi.com]

  FOXN1 Inmunodeficiencia de células T, alopecia congénita y distrofia de las uñas AR DESCRIPCIÓN Inmunodeficiencia de células T, alopecia congénita y distrofia de las uñas: Anim pariatur cliche reprehenderit, enim eiusmod high life accusamus terry richardson [genaden.com]

• Skin Disease

  Skin disease showed a continuous improvement (Figure 1j and k), but at the age of 16 years she still has sparse, brittle hair and developed myopia (Figure 1j and k). [nature.com]

• Blue Sclera

  Blue sclerae MedGen UID: 154236 •Concept ID: C0542514 • Finding An abnormal bluish coloration of the sclera. [ncbi.nlm.nih.gov]

  Some patients also demonstrate lipodystrophy, osteoporosis/osteopenia, and blue sclera. [mdpi.com]

  sclera, large ears, and microcephaly.[5] Similarly, other ARCL syndromes such as De Barsy Syndrome (type-III ARCL), Wrinkly Skin Syndrome, which also shows mutations in PYCR1 and Geroderma osteodysplastica share phenotypic features to an extent, with [journals.lww.com]

  Affected individuals may also have distinctive facial features including an abnormally large forehead, large ears, a rounded (bulbous) nose, a protruding jaw (prognathism), bluish discoloration of the whites of the eyes (blue sclera), and a triangular-shaped [rarediseases.org]

  Generalized cutis laxa, proportionate microcephaly (OFC: 30.8 cm: −3 SD), large fontanel (4.5 × 3 cm), brachycephaly, flat face, midfacial hypoplasia, blue sclerae, strabismus, anteverted nares, long philtrum, down-slanting palpebral fissures and hyperflexible [nature.com]

• Large Fontanel

  The fontanelles gradually ossify, whereby the posterior fontanelle usually closes by eight weeks and the anterior fontanelle by the 9th to 16th month of age. Large fontanelles are diagnosed if the fontanelles are larger than age-dependent norms. [ncbi.nlm.nih.gov]

  Progressive microcephaly is quite unique in view of the finding of a large and persistent open fontanel. Congenital central nervous system anomalies are found only in the minority of the patients. [nature.com]

/ 778068007 SNOMEDCT-ES (treatment) / 778068007 distrofia muscular de las cinturas de las extremidades tipo 2A autosómica recesiva Leyden-Möbius muscular dystrophy SNOMEDCT-ES (trastorno) / 715341003 SNOMEDCT-ES (treatment) / 715341003 www.wordscope.com [wordscope.com]

Their research focuses on identifying the genetic causes of cutis laxa in an effort to better understand the effect of gene mutations and develop new treatments. Use the provided contact information to learn more. [rareguru.com]

The causes of acquired cutis laxa are unclear, although it may occur after an infection or an episode of inflammation in the skin (such as eczema or hives), or as a side effect of treatment with certain medications, such as those that remove copper from [medlineplus.gov]

Additional symptoms may eventually develop including dystonia, a group of movement disorders that vary in their symptoms, causes, progression, and treatments. [rarediseases.org]

Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis. [rarediseases.org]

PMID: 24035636 Prognosis Fischer-Zirnsak B, Koenig R, Alisch F, Güneş N, Hausser I, Saha N, Beck-Woedl S, Haack TB, Thiel C, Kamrath C, Tüysüz B, Henning S, Mundlos S, Hoffmann K, Horn D, Kornak U J Hum Genet 2019 Jul;64(7):609-616. [ncbi.nlm.nih.gov]

In addition, some subtypes of cutis laxa have only been reported in a handful of individuals, which prevents physicians from developing a complete picture of associated symptoms and prognosis. [rarediseases.org]