Perinatal HPP presents with clinical features noted either at birth or in utero based on prenatal ultrasound. [mayoclinic.org]

Achondrogenesis type II (autosomal dominant) is less severe and presents later in gestation than type I, often with polyhydramnios. [ncbi.nlm.nih.gov]

We present an infant with an enlarged anterior fontanelle, soft calvarium, fractures, respiratory distress, and seizures. Biochemical analysis showed hypercalcemia, normal serum phosphate, and low serum alkaline phosphatase (ALP) levels. [pubmed.ncbi.nlm.nih.gov]

Hypophosphatasia: nonlethal disease despite skeletal presentation in utero (17 new cases and literature review). J Bone Miner Res. 2011;26:2389-2398. http://www.ncbi.nlm.nih.gov/pubmed/21713987 Stevenson DA, Carey JC, Coburn SP, et al. [rarediseases.org]

HPP is classified according to age of presentation, with the perinatal form (inherited in an autosomal recessive manner) being the most severe [2]. [karger.com]

• Short Finger

  Anteroposterior radiograph in the most severe form of the disease shows short limbs, short ribs, deficient ossification of the pelvis and skull, and “beaded” ribs due to healing fractures (arrow). [ncbi.nlm.nih.gov]

• Failure to Thrive

  The initial problem may be the baby’s failure to gain weight and grow as expected, referred to as “failure to thrive.” Sometimes the skull bones fuse, called craniosynostosis, which can lead to a deformed head (brachycephaly). [rarediseases.org]

• Low Set Ears

  […] feet Very small hands and feet Trident hands Brachydactyly Other Generalized hypomineralization Decreased echogenicity of bones Small for gestational age Polyhydramnios Generalized hypomineralization Normal bone density Micrognathia Flat nasal bridge Low-set [ncbi.nlm.nih.gov]

• Short Hands

  […] and feet Underossification and sonolucency of hands Hands appear grossly normal and are echogenic Short fingers and toes Clubbed feet Very small hands and feet Trident hands Brachydactyly Other Generalized hypomineralization Decreased echogenicity of [ncbi.nlm.nih.gov]

• Macrocephaly

  Hypochondrogenesis is characterized by a small thorax, short limbs, a flat face with micrognathia, a short trunk and macrocephaly, a flat nose and depressed nasal bridge [27]. Radiographic features in a female fetus with achondrogenesis type IA. [ncbi.nlm.nih.gov]

• Brachydactyly

  Characteristic in utero sonographic features of thanatophoric dysplasia include severe micromelia and brachydactyly, bowed (type I) or straight (type II) long bones, severe platyspondyly with normal trunk length, narrow thorax, short ribs and prominent [ncbi.nlm.nih.gov]

• Short Trunk

  Hypochondrogenesis is characterized by a small thorax, short limbs, a flat face with micrognathia, a short trunk and macrocephaly, a flat nose and depressed nasal bridge [27]. Radiographic features in a female fetus with achondrogenesis type IA. [ncbi.nlm.nih.gov]

• Bowing of Tibia

  […] of the long bones Angulation (tibiae and short fibula) Mild to moderate bowing Diaphyseal spurs (tibial dimple) Hypoplastic fibulae Micromelia Metaphyseal spikes Dysplastic limbs Bowed limbs Diaphyseal spurs Micromelia Femoral bowing (type I) Thorax [ncbi.nlm.nih.gov]

• Short Neck

  Achondrogenesis types IA/B are inherited by autosomal-recessive transmission and are associated with extreme micromelia, short hands and feet, poor mineralization, a large head, a flat face and a short neck. [ncbi.nlm.nih.gov]

• Delayed Closure of Fontanelles

  Cleidocranial dysplasia Cleidocranial dysplasia is an autosomal-dominant skeletal dysplasia characterized by clavicular hypoplasia or aplasia, delayed closure of fontanelles and sutures, and hypoplasia of the pubic bones (Table 2) (Fig. 21) [64]. [ncbi.nlm.nih.gov]

• Depressed Nasal Bridge

  bridge Low-set ears Nuchal edema Early hydrops Cystic hygroma Short crown–rump length Polyhydramnios (type II) Omphalocele Normal trunk length Depressed nasal bridge Hydrocephaly Polyhydramnios Radiographic features in a 22 weeks’ gestation male fetus [ncbi.nlm.nih.gov]

Clinical Testing and Workup HPP is sometimes first suspected from routine testing of blood that includes assay of alkaline phosphatase (ALP). [rarediseases.org]

Treatment Asfotase alfa is approved for the treatment of children with HPP and for adults with childhood-onset disease. [mayoclinic.org]

Safety and efficacy of treatment with asfotase alfa in patients with hypophosphatasia: results from a Japanese clinical trial. Clin Endocrinol (Oxf). 2017; 87(1):10-9. [pubmed.ncbi.nlm.nih.gov]

Supportive treatments for HPP are directed toward specific symptoms and complications. Treatment may require a team of specialists. [rarediseases.org]

Improvement is still being observed in the patients receiving continued asfotase alfa therapy, with more than 3 years of treatment in some children. [osteologia.org.ar]

The family should receive counseling by a clinician familiar with the treatment of children with HPP so that they are informed on available treatment options before making decisions about terminating the pregnancy. [ncbi.nlm.nih.gov]

These patients have a better prognosis in the perinatal period than patients with perinatal or infantile HPP, which may be fatal [49, 50, 52]. [ncbi.nlm.nih.gov]

[…] irregularities osteochondral projections of the midshaft of the fibula and ulna bifid diaphyses 1 Ancillary antenatal imaging features include polyhydramnios on ultrasound poor rib mineralization is seen as lack of normal bony reflectivity Treatment and prognosis [radiopaedia.org]

The clinical presentation of HPP is highly variable, and the prognosis for the infantile form is poor. Case presentation This study reports a male infant diagnosed with lethal perinatal HPP. [bmcpediatr.biomedcentral.com]

"In cases of prenatally identified HPP, genetic diagnosis is important to rule out other genetic etiologies of low bone mass," highlights David R. Deyle, M.D., Medical Genetics, at Mayo Clinic in Rochester, Minnesota. [mayoclinic.org]

Administration of mineral-targeting TNAP from birth increased survival and prevented the seizures, rickets, as well as all the tooth abnormalities, including dentin, acelular cementum, and enamel defects, in this model of severe HPP. [osteologia.org.ar]